HIV AIDS medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{AIDS}}
{{AIDS}}
{{CMG}}; {{AE}} {{AL}}
{{CMG}}; {{AE}} {{AL}}; {{Ammu}}; {{TarekNafee}}
==Overview==
==Overview==
The primary goal of [[antiretroviral therapy]] (ART) is to reduce HIV-associated [[morbidity]] and [[mortality]]. This goal is best accomplished by using effective ART to maximally inhibit HIV replication, as defined by achieving and maintaining [[plasma]] [[HIV]] [[RNA]] ([[viral load]]) below levels detectable by commercially available [[assay]]s. Durable viral suppression improves immune function and quality of life, lowers the risk of both AIDS-defining and non-AIDS-defining complications, and prolongs life. Based on emerging evidence, additional benefits of ART include a reduction in HIV-associated [[inflammation]] and possibly its associated complications.
The primary goal of [[antiretroviral therapy]] (ART) is to reduce HIV-associated [[morbidity]] and [[mortality]]. This goal is best accomplished by using highly-active ART to maximally inhibit HIV replication, as defined by achievement and maintenance of [[plasma]] [[HIV]] [[RNA]] ([[viral load]]) below detectable levels, restoration of normal CD4 cell count, and prevention of transmission of the disease. Major classes of agents used in the treatment of HIV are: [[Non-nucleoside reverse transcriptase inhibitors]] (NNRTIs), [[nucleoside reverse transcriptase inhibitors]] (NRTIs), [[protease inhibitors]] (PIs), [[fusion inhibitor]]s, [[CCR5]] antagonists, and [[integrase inhibitors]]. All regimens are combinations of at least 3 agents, preferably with 2 NRTIs. Durable viral suppression improves immune function and quality of life, lowers the risk of both AIDS-defining and non-AIDS-defining complications, and prolongs life. Based on emerging evidence, additional benefits of ART include a reduction in HIV-associated [[inflammation]] and its associated complications.


==Medical Therapy==
==Medical Therapy==
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The six classes are as follows:
The six classes are as follows:


# [[Non-nucleoside reverse transcriptase inhibitors]] (NNRTIs).
#[[Non-nucleoside reverse transcriptase inhibitors]] (NNRTIs).
# [[Nucleoside reverse transcriptase inhibitors]] (NRTIs).
#[[Nucleoside reverse transcriptase inhibitors]] (NRTIs).
# [[Protease inhibitors]] (PIs).
#[[Protease inhibitors]] (PIs).
# [[Fusion inhibitor]]s.
#[[Fusion inhibitor]]s.
# [[CCR5]] antagonists.
#[[CCR5]] antagonists.
# [[Integrase inhibitors]].
#[[Integrase inhibitors]].


Multidrug regimen has proved to be very beneficial because of reduction in progression to AIDS, opportunistic infections, rate of hospitalizations and deaths. <ref name="pmid16054937">{{cite journal |author=Sterne JA, Hernán MA, Ledergerber B, Tilling K, Weber R, Sendi P, Rickenbach M, Robins JM, Egger M |title=Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study |journal=Lancet |volume=366 |issue=9483 |pages=378–84 |year=2005 |pmid=16054937 |doi=10.1016/S0140-6736(05)67022-5 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(05)67022-5 |accessdate=2012-02-15}}</ref>
Multidrug regimen has proved to be very beneficial because of reduction in progression to AIDS, opportunistic infections, rate of hospitalizations and deaths. <ref name="pmid16054937">{{cite journal |author=Sterne JA, Hernán MA, Ledergerber B, Tilling K, Weber R, Sendi P, Rickenbach M, Robins JM, Egger M |title=Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study |journal=Lancet |volume=366 |issue=9483 |pages=378–84 |year=2005 |pmid=16054937 |doi=10.1016/S0140-6736(05)67022-5 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(05)67022-5 |accessdate=2012-02-15}}</ref>


===Goals of Therapy===
===Goals of Therapy===
* Durable suppression of HIV [[viral load]] ( to <50 cells/mL ).
 
* Restoration of normal CD4 cell count.
*Durable suppression of HIV [[viral load]] ( to <50 cells/mL ).
* Prevention of transmission of the disease.
*Restoration of normal CD4 cell count.
* Prevention of building of [[drug resistance]].
*Prevention of transmission of the disease.
* Improvement in quality of life of the patient.
*Prevention of building of [[drug resistance]].
*Improvement in quality of life of the patient.


Uncontrolled [[viremia]] causes [[inflammation]] and immune activation, which has an overall effect on [[cardiovascular]], [[renal]] and [[hepatic]] systems. Controlling viremia also controls these effects.
Uncontrolled [[viremia]] causes [[inflammation]] and immune activation, which has an overall effect on [[cardiovascular]], [[renal]] and [[hepatic]] systems. Controlling viremia also controls these effects.


===Anti Retroviral Therapy (ART)===
===Anti Retroviral Therapy (ART)===
*Current optimal HAART options consist of drug combinations consisting of at least three drugs belonging to at least two classes of [[antiretroviral]] agents.  
 
*Current optimal HAART options consist of drug combinations consisting of at least three drugs belonging to at least two classes of [[antiretroviral]] agents.
*Typical regimens consist of:
*Typical regimens consist of:
:* Two [[nucleoside analogue reverse transcriptase inhibitor]]s (NARTIs or NRTIs) '''PLUS'''
 
:* Either a [[protease inhibitor (pharmacology)|protease inhibitor]] or a [[non-nucleoside reverse transcriptase inhibitor]] (NNRTI).  
:*Two [[nucleoside analogue reverse transcriptase inhibitor]]s (NARTIs or NRTIs) '''PLUS'''
:*Either a [[protease inhibitor (pharmacology)|protease inhibitor]] or a [[non-nucleoside reverse transcriptase inhibitor]] (NNRTI).
 
*In treatment-naive patients, four drug regimen is not found to be more efficacious than three-drug regimens and is associated with more adverse events.<ref name="pmid14668456">{{cite journal |author=Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Johnson VA, Morse GD, Nokta MA, Martinez AI, Gripshover BM, Kaul P, Haubrich R, Swingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC |title=Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection |journal=N. Engl. J. Med. |volume=349 |issue=24 |pages=2304–15 |year=2003 |month=December |pmid=14668456 |doi=10.1056/NEJMoa030265 |url=http://dx.doi.org/10.1056/NEJMoa030265 |accessdate=2012-02-16}}</ref><ref name="pmid20735258">{{cite journal |author=Puls RL, Srasuebkul P, Petoumenos K, Boesecke C, Duncombe C, Belloso WH, Molina JM, Li L, Avihingsanon A, Gazzard B, Cooper DA, Emery S |title=Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study |journal=Clin. Infect. Dis. |volume=51 |issue=7 |pages=855–64 |year=2010 |month=October |pmid=20735258 |doi=10.1086/656363 |url=http://www.cid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=20735258 |accessdate=2012-02-16}}</ref>
*In treatment-naive patients, four drug regimen is not found to be more efficacious than three-drug regimens and is associated with more adverse events.<ref name="pmid14668456">{{cite journal |author=Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Johnson VA, Morse GD, Nokta MA, Martinez AI, Gripshover BM, Kaul P, Haubrich R, Swingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC |title=Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection |journal=N. Engl. J. Med. |volume=349 |issue=24 |pages=2304–15 |year=2003 |month=December |pmid=14668456 |doi=10.1056/NEJMoa030265 |url=http://dx.doi.org/10.1056/NEJMoa030265 |accessdate=2012-02-16}}</ref><ref name="pmid20735258">{{cite journal |author=Puls RL, Srasuebkul P, Petoumenos K, Boesecke C, Duncombe C, Belloso WH, Molina JM, Li L, Avihingsanon A, Gazzard B, Cooper DA, Emery S |title=Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study |journal=Clin. Infect. Dis. |volume=51 |issue=7 |pages=855–64 |year=2010 |month=October |pmid=20735258 |doi=10.1086/656363 |url=http://www.cid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=20735258 |accessdate=2012-02-16}}</ref>


*Antiretroviral therapy should be initiated in the following patient populations:
*[[Fusion inhibitor]]s (eg, [[enfuvirtide]]) are not approved for treatment-naive patients.


:* Patients with history of an AIDS-defining illness or with a [[CD4]] count of less than 350/µL.
===Anti Retroviral Regimens===
:* Pregnant women with HIV [[infection]].
====WHO Recommendations in Adults====
:* Patients with [[HIV associated nephropathy]].
<SMALL><font color="#FF4C4C">'''▸ Click on the following categories to expand treatment regimens.'''</font></SMALL>
:* Patients with HIV and [[hepatitis B virus]] (HBV) coinfection who require treatment for HBV infection.
{|
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<div style="border-radius: 5px 5px 0 0; border: solid 1px #20538D; border-bottom: 0px; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 260px; background: #A1BCDD; text-align: center;">
<font color="#FFF">
'''ARV Regimens'''
</font>
</div>


*[[Fusion inhibitor]]s (eg, [[enfuvirtide]]) are not approved for treatment-naive patients.
<div class="mw-customtoggle-table10" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 260px; background: #4479BA;">
<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''First-Line Regimens'''
</font>
</div>


*Treatment failure is defined by the following factors:
<div class="mw-customtoggle-table11" style="cursor: pointer; border-radius: 0 0 5px 5px; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 260px; background: #4479BA;">
:* '''Virologic failure''': which is defined as suboptimal viral suppression or loss of suppression (>50 HIV-1 RNA copies/mL).
<font color="#FFF">
:* '''Immunologic failure ''': which is defined as failure to achieve or maintain [[CD4]] cell count recovery despite effective viral suppression.
&nbsp;&nbsp;▸&nbsp;&nbsp;'''Second-Line Regimens'''
:* Development of new [[opportunistic infection]]s or [[neoplasm]]s despite apparent CD4 count recovery.
</font>
</div>


====Anti Retroviral Regimens====
| valign="top" |
{| class="mw-collapsible mw-collapsed" style="background: #FFFFFF;"
| valign="top" |
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align="center" |{{fontcolor|#FFF|First-line Regimen}}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''Preferred Regimen'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Emtricitabine]] (FTC)'''<BR> OR <br>▸ '''[[Lamivudine]] (3TC)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Tenofovir]] (TDF)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Efavirenz]] (EFV)'''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''Alternative Regimen 1 <br> <small> (If preferred regimen is contraindicated or not available)</small>'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Zidovudine]] (AZT)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Lamivudine]] (3TC)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Efavirenz]] (EFV)'''<BR> OR <br>▸ '''[[Nevirapine]] (NVP)'''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''Alternative Regimen 2 <br> <small> (If preferred regimen is contraindicated or not available)</small>'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Tenofovir]] (TDF)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Emtricitabine]] (FTC)'''<BR> OR <br>▸ '''[[Lamivudine]] (3TC)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Nevirapine]] (NVP)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small>Adapted from WHO 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection  <ref name="WHO HIV1"> {{cite web| url=http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf| title= WHO 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection }} </ref></small>
|}
|}
{| class="mw-collapsible mw-collapsed" style="background: #FFFFFF;"
| valign="top" |
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align="center" |{{fontcolor|#FFF|Second-line Regimen}}
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''If TDF + 3TC based regimen failed'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Zidovudine]] (ZDV)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Lamivudine]] (3TC)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''Ritonavir-boosted [[Atazanavir]] (ATV/r)'''<BR> OR <br>▸ '''Ritonavir-boosted [[Lopinavir]] (LPV/r)'''
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''If ZDV + 3TC based regimen failed'''''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Tenofovir]] (TDF)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Lamivudine]] (3TC)'''
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |PLUS
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''Ritonavir-boosted [[Atazanavir]] (ATV/r)'''<BR> OR <br>▸ '''Ritonavir-boosted [[Lopinavir]] (LPV/r)'''
|-
|}
|}
|}
 
====National Institute of Health (NIH) Recommendations====  
<SMALL><font color="#FF4C4C">'''▸ Click on the following categories to expand treatment regimens.'''</font></SMALL>
<SMALL><font color="#FF4C4C">'''▸ Click on the following categories to expand treatment regimens.'''</font></SMALL>


{|
{|
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| valign="top" |
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<div style="border-radius: 5px 5px 0 0; border: solid 1px #20538D; border-bottom: 0px; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 260px; background: #A1BCDD; text-align: center;">
<font color="#FFF">
<font color="#FFF">
'''Recommended Regimens'''
'''Recommended Regimens'''
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<div class="mw-customtoggle-table01" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 260px; background: #4479BA;">
<font color="#FFF">
<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''NNRTI-Based Regimen'''
&nbsp;&nbsp;▸&nbsp;&nbsp;'''NNRTI-Based Regimen'''
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<div class="mw-customtoggle-table02" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 260px; background: #4479BA;">
<font color="#FFF">
<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''PI-Based Regimen'''
&nbsp;&nbsp;▸&nbsp;&nbsp;'''PI-Based Regimen'''
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<div class="mw-customtoggle-table03" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 260px; background: #4479BA;">
<font color="#FFF">
<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''INSTI-Based Regimen'''
&nbsp;&nbsp;▸&nbsp;&nbsp;'''INSTI-Based Regimen'''
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<div style="border-radius: 0 0 0 0; border: solid 1px #20538D; border-bottom: 0px; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 260px; background: #A1BCDD; text-align: center;">
<font color="#FFF">
<font color="#FFF">
'''Alternative Regimens'''
'''Alternative Regimens'''
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<div class="mw-customtoggle-table04" style="cursor: pointer; border-radius: 0 0 0 0; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 260px; background: #4479BA;">
<font color="#FFF">
<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''PI-Based Regimen'''
&nbsp;&nbsp;▸&nbsp;&nbsp;'''PI-Based Regimen'''
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<div class="mw-customtoggle-table05" style="cursor: pointer; border-radius: 0 0 5px 5px; border: solid 1px #20538D; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5); box-shadow: inset 0 1px 1px rgba(255, 255, 255, 0.5), 0 1px 1px rgba(0, 0, 0, 0.5); height: 30px; line-height: 30px; width: 260px; background: #4479BA;">
<font color="#FFF">
<font color="#FFF">
&nbsp;&nbsp;▸&nbsp;&nbsp;'''INSTI-Based Regimen'''
&nbsp;&nbsp;▸&nbsp;&nbsp;'''INSTI-Based Regimen'''
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{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Recommended Regimen}}
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align="center" |{{fontcolor|#FFF|Recommended Regimen}}
|-
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''NNRTI-Based Regimen'''''
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''NNRTI-Based Regimen'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left |▸ '''Efavirenz/Tenofovir/Emtricitabine<sup>†</sup>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Efavirenz]]/[[Tenofovir]]/[[Emtricitabine]]<sup>†</sup>'''
|-
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''NNRTI-based regimen for patients with HIV RNA < 100,000 copies/mL'''''
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''NNRTI-based regimen for patients with < 100,000 copies/mL'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''Efavirenz''' <br> PLUS <br> ▸ '''Abacavir/Lamivudine<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Efavirenz]]''' <br> PLUS <br> ▸ '''[[Abacavir]]/[[Lamivudine]]<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | OR
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |OR
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''Rilpivirine/Tenofovir/Emtricitabine<sup>†</sup> <small>(only for patients with CD4 < 200 cells/mm³)</small>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Rilpivirine]]/[[Tenofovir]]/[[Emtricitabine]]<sup>†</sup> <small>(only for patients with CD4 < 200 cells/mm³)</small>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left |<small><sup>†</sup>Emtricitabine may be substituted for lamivudine or vice versa</small>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small><sup>†</sup>Emtricitabine may be substituted for lamivudine or vice versa</small>
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left | <small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
|}
|}
|}
|}
{| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table02" style="background: #FFFFFF;"
{| class="mw-collapsible mw-collapsed" style="background: #FFFFFF;"
| valign=top |
| valign="top" |
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Recommended Regimen}}
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align="center" |{{fontcolor|#FFF|Recommended Regimen}}
|-
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''PI-Based Regimen'''''
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''PI-Based Regimen'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left |▸ '''Atazanavir/Ritonavir(low dose)''' <br> PLUS <br> ▸ '''Tenofovir/Emtricitabine<sup>†</sup>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Atazanavir]]/[[Ritonavir]](low dose)''' <br> PLUS <br> ▸ '''[[Tenofovir]]/[[Emtricitabine]]<sup>†</sup>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | OR
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |OR
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left |▸ '''Darunavir/Ritonavir(low dose)''' <br> PLUS <br> ▸ '''Tenofovir/Emtricitabine<sup>†</sup>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Darunavir]]/[[Ritonavir]](low dose)''' <br> PLUS <br> ▸ '''[[Tenofovir]]/Emtricitabine<sup>†</sup>'''
|-
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''PI-based regimen for patients with HIV RNA < 100,000 copies/mL'''''  
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''PI-based regimen for patients with < 100,000 copies/mL'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | OR
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |OR
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left |▸ '''Atazanavir/Ritonavir(low dose)''' <br> PLUS <br> ▸ '''Abacavir/Lamivudine<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Atazanavir]]/[[Ritonavir]](low dose)''' <br> PLUS <br> ▸ '''[[Abacavir]]/[[Lamivudine]]<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left |<small><sup>†</sup>Emtricitabine may be substituted for lamivudine or vice versa</small>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small><sup>†</sup>[[Emtricitabine]] may be substituted for [[lamivudine]] or vice versa</small>
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left | <small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
|-
|-
|}
|}
|}
|}
{| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table03" style="background: #FFFFFF;"
{| class="mw-collapsible mw-collapsed" style="background: #FFFFFF;"
| valign=top |
| valign="top" |
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Recommended Regimen}}
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align="center" |{{fontcolor|#FFF|Recommended Regimen}}
|-
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''INSTI-Based Regimen'''''
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''INSTI-Based Regimen'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left |▸ '''Dolutegravir ''' <br> PLUS <br> ▸ '''Abacavir/Lamivudine<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Dolutegravir]] ''' <br> PLUS <br> ▸ '''[[Abacavir]]/[[Lamivudine]]<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | OR
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |OR
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left |▸ '''Dolutegravir ''' <br> PLUS <br> ▸ '''Tenofovir/Emtricitabine<sup>†</sup>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Dolutegravir]] ''' <br> PLUS <br> ▸ '''[[Tenofovir]]/[[Emtricitabine]]<sup>†</sup>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | OR
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |OR
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left |▸ '''Elvitegravir/Cobicistat/Tenofovir/Emtricitabine<sup>†</sup><small>(contraindicated in patients with CrCl <70mL/min)</small>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Elvitegravir]]/[[Cobicistat]]/[[Tenofovir]]/[[Emtricitabine]]<sup>†</sup><small>(contraindicated in patients with CrCl <70mL/min)</small>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | OR
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |OR
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left |▸ '''Raltegravir''' <br> PLUS <br> ▸ '''Tenofovir/Emtricitabine<sup>†</sup>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Raltegravir]]''' <br> PLUS <br> ▸ '''[[Tenofovir]]/[[Emtricitabine]]<sup>†</sup>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left |<small><sup>†</sup>Emtricitabine may be substituted for lamivudine or vice versa</small>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small><sup>†</sup>[[Emtricitabine]] may be substituted for [[lamivudine]] or vice versa</small>
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left | <small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.<ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.<ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
|}
|}
|}
|}
{| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table04" style="background: #FFFFFF;"
{| class="mw-collapsible mw-collapsed" style="background: #FFFFFF;"
| valign=top |
| valign="top" |
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Alternative Regimen}}
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align="center" |{{fontcolor|#FFF|Alternative Regimen}}
|-
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''PI-Based Regimens'''''
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''PI-Based Regimens'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''Darunavir/Ritonavir(low dose)''' <br> PLUS <br> ▸ '''Abacavir/Lamivudine<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Darunavir]]/[[Ritonavir]](low dose)''' <br> PLUS <br> ▸ '''[[Abacavir]]/[[Lamivudine]]<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | OR
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |OR
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''Lopinavir/Ritonavir(low dose)''' <br> PLUS <br> ▸ '''Abacavir/Lamivudine<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Lopinavir]]/[[Ritonavir]](low dose)''' <br> PLUS <br> ▸ '''[[Abacavir]]/[[Lamivudine]]<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | OR
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |OR
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''Lopinavir/Ritonavir(low dose)''' <br> PLUS <br> ▸'''Tenofovir/Emtricitabine<sup>†</sup>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Lopinavir]]/[[Ritonavir]](low dose)''' <br> PLUS <br> ▸'''[[Tenofovir]]/[[Emtricitabine]]<sup>†</sup>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left |<small><sup>†</sup>Emtricitabine may be substituted for lamivudine or vice versa</small>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small><sup>†</sup>[[Emtricitabine]] may be substituted for [[lamivudine]] or vice versa</small>
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left | <small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
|}
|}
|}
|}
{| class="mw-collapsible mw-collapsed" id="mw-customcollapsible-table05" style="background: #FFFFFF;"
{| class="mw-collapsible mw-collapsed" style="background: #FFFFFF;"
| valign=top |
| valign="top" |
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
{| style="float: left; cellpadding=0; cellspacing= 0; width: 400px;"
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align=center | {{fontcolor|#FFF|Alternative Regimen}}
! style="height: 30px; line-height: 30px; background: #4479BA; border: 0px; font-size: 100%; text-shadow: 0 -1px 0 rgba(0, 0, 0, 0.5);" align="center" |{{fontcolor|#FFF|Alternative Regimen}}
|-
|-
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align=center | '''''INSTI-Based Regimens'''''
| style="padding: 0 5px; font-size: 90%; background: #F5F5F5;" align="center" |'''''INSTI-Based Regimens'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align=left | ▸ '''Raltegravir''' <br> PLUS <br> ▸ '''Abacavir/Lamivudine<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
| style="font-size: 90%; padding: 0 5px; background: #DCDCDC;" align="left" |▸ '''[[Raltegravir]]''' <br> PLUS <br> ▸ '''[[Abacavir]]/[[Lamivudine]]<sup>†</sup> <small>(only for HLA-B*5701 negative patients)</small>'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left |<small><sup>†</sup>Emtricitabine may be substituted for lamivudine or vice versa</small>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small><sup>†</sup>[[Emtricitabine]] may be substituted for [[lamivudine]] or vice versa</small>
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left | <small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
|}
|}
|}
|}
|}
|}
===Anti Retroviral Drug Classes===
===Anti Retroviral Drug Classes===
{| style="border: 0px; font-size: 90%; margin: 3px; width: 900px;" align=center
{| style="border: 0px; font-size: 90%; margin: 3px; width: 900px;" align="center"
|valign=top|
| valign="top" |
|+
|+
! style="background: #4479BA; color:#FFF;  width: 200px;" | Drug Name
! style="background: #4479BA; color:#FFF;  width: 200px;" |Drug Name
! style="background: #4479BA; color:#FFF;  width: 350px;" | Dose
! style="background: #4479BA; color:#FFF;  width: 350px;" |Dose
! style="background: #4479BA; color:#FFF;  width: 350px;" | Adverse Events
! style="background: #4479BA; color:#FFF;  width: 350px;" |Adverse Events
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" colspan=3 |Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
| colspan="3" style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Abacavir]] (ABC)
*[[Abacavir]] (ABC)
| style="padding: 5px 5px; background: #F5F5F5;" | '''300 mg BID or 600 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''300 mg BID or 600 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Fever]], [[rash]], [[nausea]], [[vomiting]], [[diarrhea]], [[abdominal pain]], [[malaise]], [[fatigue]], [[sore throat]], [[cough]], [[shortness of breath]].
| style="padding: 5px 5px; background: #F5F5F5;" |[[Fever]], [[rash]], [[nausea]], [[vomiting]], [[diarrhea]], [[abdominal pain]], [[malaise]], [[fatigue]], [[sore throat]], [[cough]], [[shortness of breath]].
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
Line 239: Line 332:
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Lamivudine]] (3TC)
*[[Lamivudine]] (3TC)
| style="padding: 5px 5px; background: #F5F5F5;" | '''150 mg BID''' or '''300 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''150 mg BID''' or '''300 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |Minimal toxicity, severe acute exacerbation of hepatitis may occur in [[HBV]] coinfected patients who discontinue 3TC.
| style="padding: 5px 5px; background: #F5F5F5;" |Minimal toxicity, severe acute exacerbation of hepatitis may occur in [[HBV]] coinfected patients who discontinue 3TC.
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Stavudine]] (d4T)
*[[Stavudine]] (d4T)
| style="padding: 5px 5px; background: #F5F5F5;" | >60 kg: '''40 mg BID''' <br> <60 kg: '''250 mg BID'''
| style="padding: 5px 5px; background: #F5F5F5;" |>60 kg: '''40 mg BID''' <br> <60 kg: '''250 mg BID'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Peripheral neuropathy]], [[lipoatrophy]], [[pancreatitis]], [[lactic acidosis]], severe [[hepatomegaly]] with [[hepatic steatosis]] (rare), [[hyperlipidemia]], [[insulin resistance]]/[[diabetes mellitus]], rapidly progressive ascending neuromuscular weakness (rare).
| style="padding: 5px 5px; background: #F5F5F5;" |[[Peripheral neuropathy]], [[lipoatrophy]], [[pancreatitis]], [[lactic acidosis]], severe [[hepatomegaly]] with [[hepatic steatosis]] (rare), [[hyperlipidemia]], [[insulin resistance]]/[[diabetes mellitus]], rapidly progressive ascending neuromuscular weakness (rare).
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Tenofovir Disoproxil Fumarate]] (TDF)
*[[Tenofovir Disoproxil Fumarate]] (TDF)
| style="padding: 5px 5px; background: #F5F5F5;" | '''300 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''300 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Renal insufficiency]], [[Fanconi syndrome]], [[osteomalacia]], decrease in bone mineral density, severe acute exacerbation of
| style="padding: 5px 5px; background: #F5F5F5;" |[[Renal insufficiency]], [[Fanconi syndrome]], [[osteomalacia]], decrease in bone mineral density, severe acute exacerbation of [[hepatitis]] may occur in [[HBV]] coinfected patients who discontinue TDF, [[asthenia]], [[headache]], [[diarrhea]], [[nausea]], [[vomiting]], and [[flatulence]].
[[hepatitis]] may occur in [[HBV]] coinfected patients who discontinue TDF, [[asthenia]], [[headache]], [[diarrhea]], [[nausea]], [[vomiting]], and [[flatulence]].
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" colspan=3|Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
| colspan="3" style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Efavirenz]](EFV)
*[[Efavirenz]](EFV)
| style="padding: 5px 5px; background: #F5F5F5;" | '''600 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''600 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], increased [[transaminase]] levels, [[hyperlipidemia]], [[dizziness]], [[somnolence]], [[insomnia]], [[depression]], [[suicidality]], [[confusion]], abnormal thinking, impaired concentration, [[amnesia]], [[agitation]], [[depersonalization]], [[hallucinations]], and [[euphoria]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], increased [[transaminase]] levels, [[hyperlipidemia]], [[dizziness]], [[somnolence]], [[insomnia]], [[depression]], [[suicidality]], [[confusion]], abnormal thinking, impaired concentration, [[amnesia]], [[agitation]], [[depersonalization]], [[hallucinations]], and [[euphoria]]
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Etravirine]] (ETR)
*[[Etravirine]] (ETR)
| style="padding: 5px 5px; background: #F5F5F5;" | '''200 mg BID'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''200 mg BID'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], [[Stevens-Johnson syndrome]], [[nausea]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], [[Stevens-Johnson syndrome]], [[nausea]]
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Nevirapine]] (NVP)
*[[Nevirapine]] (NVP)
| style="padding: 5px 5px; background: #F5F5F5;" | '''200 mg once daily''' for 14 days, then '''200 mg BID or 400 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''200 mg once daily''' for 14 days, then '''200 mg BID or 400 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], [[Stevens-Johnson syndrome]], [[nausea]], [[hepatitis]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], [[Stevens-Johnson syndrome]], [[nausea]], [[hepatitis]]
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Rilpivirine]] (RPV)
*[[Rilpivirine]] (RPV)
| style="padding: 5px 5px; background: #F5F5F5;" | '''25 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''25 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], [[depression]], [[insomnia]], [[headache]], [[hepatotoxicity]]
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], [[depression]], [[insomnia]], [[headache]], [[hepatotoxicity]]
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" colspan=3 |Protease Inhibitors (PIs)
| colspan="3" style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |Protease Inhibitors (PIs)
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Atazanavir]] (ATV)
*[[Atazanavir]] (ATV)
| style="padding: 5px 5px; background: #F5F5F5;" | '''400 mg once daily'''<br> In combination with TDF: '''300 mg''' + RTV 100 mg once daily <br>In combination with EFV: '''400 mg''' + RTV 100 mg once daily
| style="padding: 5px 5px; background: #F5F5F5;" |'''400 mg once daily'''<br> In combination with TDF: '''300 mg''' + RTV 100 mg once daily <br>In combination with EFV: '''400 mg''' + RTV 100 mg once daily
| style="padding: 5px 5px; background: #F5F5F5;" |Indirect [[hyperbilirubinemia]], [[PR interval]] prolongation, [[hyperglycemia]], fat maldistribution, [[cholelithiasis]], [[nephrolithiasis]], [[renal insufficiency]], increase in [[transaminase]] levels, [[hyperlipidemia]], [[skin rash]]
| style="padding: 5px 5px; background: #F5F5F5;" |Indirect [[hyperbilirubinemia]], [[PR interval]] prolongation, [[hyperglycemia]], fat maldistribution, [[cholelithiasis]], [[nephrolithiasis]], [[renal insufficiency]], increase in [[transaminase]] levels, [[hyperlipidemia]], [[skin rash]]
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Darunavir]] (DRV)
*[[Darunavir]] (DRV)
| style="padding: 5px 5px; background: #F5F5F5;" | '''800 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''800 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Skin rash]], [[Stevens-Johnson syndrome]], [[hepatotoxicity]], [[diarrhea]], [[nausea]], [[headache]], [[hyperlipidemia]], fat maldistribution, [[hyperglycemia]].
| style="padding: 5px 5px; background: #F5F5F5;" |[[Skin rash]], [[Stevens-Johnson syndrome]], [[hepatotoxicity]], [[diarrhea]], [[nausea]], [[headache]], [[hyperlipidemia]], fat maldistribution, [[hyperglycemia]].
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Fosamprenavir]] (FPV)
*[[Fosamprenavir]] (FPV)
| style="padding: 5px 5px; background: #F5F5F5;" | '''1400 mg BID''' or <br> '''700 mg''' + RTV 100 mg BID <br> In combination with EFV: '''700 mg''' + RTV 100 mg BID or '''1400 mg''' + RTV 300 mg once daily
| style="padding: 5px 5px; background: #F5F5F5;" |'''1400 mg BID''' or <br> '''700 mg''' + RTV 100 mg BID <br> In combination with EFV: '''700 mg''' + RTV 100 mg BID or '''1400 mg''' + RTV 300 mg once daily
| style="padding: 5px 5px; background: #F5F5F5;" |[[Skin rash]], [[diarrhea]], [[nausea]], [[vomiting]], [[headache]], [[hyperlipidemia]], [[hyperglycemia]], increase in [[transaminase]] levels, [[nephrolithiasis]], fat maldistribution.
| style="padding: 5px 5px; background: #F5F5F5;" |[[Skin rash]], [[diarrhea]], [[nausea]], [[vomiting]], [[headache]], [[hyperlipidemia]], [[hyperglycemia]], increase in [[transaminase]] levels, [[nephrolithiasis]], fat maldistribution.
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Indinavir]] (IDV)
*[[Indinavir]] (IDV)
| style="padding: 5px 5px; background: #F5F5F5;" | '''800 mg q8h'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''800 mg q8h'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Nephrolithiasis]], [[nausea]], [[hepatitis]], indirect [[hyperbilirubinemia]], [[hyperlipidemia]], [[headache]], [[asthenia]], [[blurred vision]], [[dizziness]], [[rash]], metallic taste, [[thrombocytopenia]], [[alopecia]], [[hemolytic anemia]], [[hyperglycemia]], fat maldistribution.
| style="padding: 5px 5px; background: #F5F5F5;" |[[Nephrolithiasis]], [[nausea]], [[hepatitis]], indirect [[hyperbilirubinemia]], [[hyperlipidemia]], [[headache]], [[asthenia]], [[blurred vision]], [[dizziness]], [[rash]], metallic taste, [[thrombocytopenia]], [[alopecia]], [[hemolytic anemia]], [[hyperglycemia]], fat maldistribution.
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Lopinavir ritonavir|Ritonavir-Boosted Lopinavir]] (LPV/r)
*[[Lopinavir ritonavir|Ritonavir-Boosted Lopinavir]] (LPV/r)
| style="padding: 5px 5px; background: #F5F5F5;" | '''400 mg/100 mg BID''' or '''800 mg/200 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''400 mg/100 mg BID''' or '''800 mg/200 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Diarrhea]], [[nausea]], [[vomiting]], [[pancreatitis]], [[asthenia]], [[hyperlipidemia]], [[hyperglycemia]], fat maldistribution,  increase in [[transaminase]] levels, [[PR interval]] prolongation, [[insulin resistance]]/[[diabetes mellitus]].
| style="padding: 5px 5px; background: #F5F5F5;" |[[Diarrhea]], [[nausea]], [[vomiting]], [[pancreatitis]], [[asthenia]], [[hyperlipidemia]], [[hyperglycemia]], fat maldistribution,  increase in [[transaminase]] levels, [[PR interval]] prolongation, [[insulin resistance]]/[[diabetes mellitus]].
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Nelfinavir]] (NFV)
*[[Nelfinavir]] (NFV)
| style="padding: 5px 5px; background: #F5F5F5;" | '''1250 md BID''' or '''750 mg TID'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''1250 md BID''' or '''750 mg TID'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Diarrhea]], [[hyperlipidemia]], [[hyperglycemia]], fat maldistribution,  increase in [[transaminase]] levels.
| style="padding: 5px 5px; background: #F5F5F5;" |[[Diarrhea]], [[hyperlipidemia]], [[hyperglycemia]], fat maldistribution,  increase in [[transaminase]] levels.
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Ritonavir]] (RTV)
*[[Ritonavir]] (RTV)
| style="padding: 5px 5px; background: #F5F5F5;" | '''100-400 mg/d q12-24h'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''100-400 mg/d q12-24h'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Diarrhea]], [[nausea]], [[vomiting]], [[paresthesia]], [[hyperlipidemia]], [[hepatitis]], [[asthenia]], taste perversion, [[hyperglycemia]], fat maldistribution.  
| style="padding: 5px 5px; background: #F5F5F5;" |[[Diarrhea]], [[nausea]], [[vomiting]], [[paresthesia]], [[hyperlipidemia]], [[hepatitis]], [[asthenia]], taste perversion, [[hyperglycemia]], fat maldistribution.
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
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| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Tipranavir]] (TPV)
*[[Tipranavir]] (TPV)
| style="padding: 5px 5px; background: #F5F5F5;" | '''500 mg BID'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''500 mg BID'''
| style="padding: 5px 5px; background: #F5F5F5;" | [[Hepatotoxicity]], [[skin rash]], [[hyperlipidemia]], [[hyperglycemia]], fat maldistribution.
| style="padding: 5px 5px; background: #F5F5F5;" |[[Hepatotoxicity]], [[skin rash]], [[hyperlipidemia]], [[hyperglycemia]], fat maldistribution.
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" colspan=3 |Integrase Inhibitors
| colspan="3" style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |Integrase Inhibitors
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Dolutegravir]] (DTG)
*[[Dolutegravir]] (DTG)
| style="padding: 5px 5px; background: #F5F5F5;" | '''50 mg q12-24h'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''50 mg q12-24h'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], [[insomnia]], [[headache]].
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], [[insomnia]], [[headache]].
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Elvitegravir]] (EVG)
*[[Elvitegravir]] (EVG)
| style="padding: 5px 5px; background: #F5F5F5;" | '''150 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''150 mg once daily'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Nausea]], [[diarrhea]], decrease bone density, severe acute exacerbation of [[hepatitis]] may occur in [[HBV]] coinfected patients.
| style="padding: 5px 5px; background: #F5F5F5;" |[[Nausea]], [[diarrhea]], decrease bone density, severe acute exacerbation of [[hepatitis]] may occur in [[HBV]] coinfected patients.
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Raltegravir]] (RAL)
*[[Raltegravir]] (RAL)
| style="padding: 5px 5px; background: #F5F5F5;" | '''400 mg BID'''
| style="padding: 5px 5px; background: #F5F5F5;" |'''400 mg BID'''
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], [[Steven-Johnson syndrome]], [[toxic epidermal necrolysis]], [[nausea]], [[headache]], [[diarrhea]], [[pyrexia]], [[CPK]] elevation.  
| style="padding: 5px 5px; background: #F5F5F5;" |[[Rash]], [[Steven-Johnson syndrome]], [[toxic epidermal necrolysis]], [[nausea]], [[headache]], [[diarrhea]], [[pyrexia]], [[CPK]] elevation.
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" colspan=3|Fusion Inhibitor
| colspan="3" style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |Fusion Inhibitor
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
Line 347: Line 439:
| style="padding: 5px 5px; background: #F5F5F5;" |Local injection reactions, increased incidence of [[bacterial pneumonia]], [[rash]], [[fever]], [[nausea]].
| style="padding: 5px 5px; background: #F5F5F5;" |Local injection reactions, increased incidence of [[bacterial pneumonia]], [[rash]], [[fever]], [[nausea]].
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" colspan=3 |CCR5 Antagonist
| colspan="3" style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |CCR5 Antagonist
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
Line 354: Line 446:
| style="padding: 5px 5px; background: #F5F5F5;" |[[Abdominal pain]], [[cough]], [[dizziness]], musculoskeletal symptoms, [[pyrexia]], [[rash]], upper respiratory tract infections, [[hepatotoxicity]].
| style="padding: 5px 5px; background: #F5F5F5;" |[[Abdominal pain]], [[cough]], [[dizziness]], musculoskeletal symptoms, [[pyrexia]], [[rash]], upper respiratory tract infections, [[hepatotoxicity]].
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left colspan=3| <small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
| colspan="3" style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
|}
|}


{| style="border: 0px; font-size: 80%; margin: 3px; width:300px;" align="right"
| valign="top" |
|+'''CDC Grading of Recommendations and Levels of Evidence'''
! style="background: #4479BA; color:#FFF;  width: 100px;" |Strength of recommendation
! style="background: #4479BA; color:#FFF;  width: 200px;" |Level of evidence
|-
| style="padding: 5px 5px; background: #F5F5F5;" |'''A.''' Strong
| style="padding: 5px 5px; background: #F5F5F5;" |'''I.''' One or more randomized trials with clinical outcomes and/or validated laboratory endpoint
|-
| style="padding: 5px 5px; background: #F5F5F5;" |'''B.''' Moderate
| style="padding: 5px 5px; background: #F5F5F5;" |'''II.''' One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes
|-
| style="padding: 5px 5px; background: #F5F5F5;" |'''C.''' Optional
| style="padding: 5px 5px; background: #F5F5F5;" |'''III.''' Expert opinion based on evaluation of other evidence
|}
====Recommendations for Initiating Antiretroviral Therapy====
====Recommendations for Initiating Antiretroviral Therapy====
*Antiretroviral therapy (ART) is recommended for all HIV-infected individuals. The strength of this recommendation varies on the basis of pretreatment CD4 cell count:
*Antiretroviral therapy (ART) is recommended for all HIV-infected individuals. The strength of this recommendation varies on the basis of pretreatment CD4 cell count:
** CD4 count <350 cells/mm3 ('''AI''')
**CD4 count <350 cells/mm3 ('''AI''')
** CD4 count 350 to 500 cells/mm3 ('''AII''')
**CD4 count 350 to 500 cells/mm3 ('''AII''')
** CD4 count >500 cells/mm3 ('''BIII''')
**CD4 count >500 cells/mm3 ('''BIII''')


*Regardless of CD4 count, initiation of ART is strongly recommended for individuals with the following conditions:
*Regardless of CD4 count, initiation of ART is strongly recommended for individuals with the following conditions:
** Pregnancy ('''AI''')
**Pregnancy ('''AI''')
** History of an AIDS-defining illness ('''AI''')
**History of an AIDS-defining illness ('''AI''')
** [[HIV associated nephropathy]] (HIVAN) ('''AII''')
**[[HIV associated nephropathy]] (HIVAN) ('''AII''')
** HIV/[[hepatitis B virus]] (HBV) coinfection ('''AII''')
**HIV/[[hepatitis B virus]] (HBV) coinfection ('''AII''')
*Effective ART also has been shown to prevent [[transmission]] of HIV from an infected individual to a sexual partner; therefore, ART should be  offered to patients who are at risk of transmitting HIV to sexual partners ('''AI''' [heterosexuals] or '''AIII''' [other transmission risk groups].
*Effective ART also has been shown to prevent [[transmission]] of HIV from an infected individual to a sexual partner; therefore, ART should be  offered to patients who are at risk of transmitting HIV to sexual partners ('''AI''' [heterosexuals] or '''AIII''' [other transmission risk groups].
* Patients starting ART should be willing and able to commit to treatment and should understand the benefits and risks of therapy and the importance of adherence ('''AIII'''). Patients may choose to postpone therapy, and providers, on a case by case basis, may elect to defer therapy on the basis of clinical and/or psychosocial factors.
*Patients starting ART should be willing and able to commit to treatment and should understand the benefits and risks of therapy and the importance of adherence ('''AIII'''). Patients may choose to postpone therapy, and providers, on a case by case basis, may elect to defer therapy on the basis of clinical and/or psychosocial factors.
 
====Current Recommended Initial Oral ART for Most Persons with HIV Infection<ref name="pmid34077645">{{cite journal| author=Saag MS| title=HIV Infection - Screening, Diagnosis, and Treatment. | journal=N Engl J Med | year= 2021 | volume= 384 | issue= 22 | pages= 2131-2143 | pmid=34077645 | doi=10.1056/NEJMcp1915826 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34077645  }}</ref>====
 
=====Bictegravir– FTC–TAF (50 mg/200 mg/25 mg),once daily as single-tablet regimen=====
 
*Adverse effects: Gastrointestinal symptoms ([[Nausea and vomiting|nausea]], [[diarrhea]]), [[headache]], [[immune reconstitution inflammatory syndrome]] ([[IRIS]]), [[lactic acidosis]], [[Fatty liver|hepatic steatosis]].
*Not recommended in patients with [[creatinine clearance]] <30 ml/min or Child–Pugh class C [[Liver function tests|liver function]], contraindicated with [[dofetilide]] or [[rifampin]], avoid divalent cations (Ca++, Mg++, Fe++), [[phenytoin]], [[carbamazepine]], and [[rifapentine]], and use with caution with [[metformin]].
 
=====Dolutegravir (50 mg),once daily=====
 
*Adverse effects: Gastrointestinal symptoms ([[Nausea and vomiting|nausea]], [[diarrhea]]), [[headache]], [[IRIS]], [[lactic acidosis]], [[Fatty liver|hepatic steatosis]].
*Not recommended in patients with [[creatinine clearance]] <30 ml/min or Child–Pugh class C liver function, contraindicated with [[dofetilide]] or [[rifampin]], avoid divalent cations (Ca++, Mg++, Fe++), [[phenytoin]], [[carbamazepine]], and [[rifapentine]], and use with caution with [[metformin]].
 
=====Plus TAF–FTC (25 mg/200 mg), once daily as single-tablet regimen=====
 
*Adverse effects: Gastrointestinal symptoms ([[Nausea and vomiting|nausea]], [[diarrhea]]), [[headache]], [[IRIS]], [[lactic acidosis]], [[Fatty liver|hepatic steatosis]].
*Not recommended in patients with [[creatinine clearance]] <30 ml/min or Child–Pugh class C liver function, contraindicated with [[dofetilide]] or [[rifampin]], avoid divalent cations (Ca++, Mg++, Fe++), [[phenytoin]], [[carbamazepine]], and [[rifapentine]], and use with caution with [[metformin]].
 
=====Plus TDF–FTC (300 mg/200 mg), once daily as single-tablet regimen=====
 
*Adverse effects: Gastrointestinal symptoms ([[Nausea and vomiting|nausea]], [[diarrhea]]), [[headache]], [[IRIS]], [[lactic acidosis]], [[Fatty liver|hepatic steatosis]].
*Not recommended in patients with [[creatinine clearance]] <30 ml/min or Child–Pugh class C [[Liver function tests|liver function]], contraindicated with [[dofetilide]] or [[rifampin]], avoid divalent cations (Ca++, Mg++, Fe++), [[phenytoin]], [[carbamazepine]], and [[rifapentine]], and use with caution with [[metformin]].
 
=====Plus TDF–3TC (300 mg/300 mg), Individual tablets each once daily=====
 
*Adverse effects: Gastrointestinal symptoms ([[Nausea and vomiting|nausea]], [[diarrhea]]), [[headache]], [[IRIS]], [[lactic acidosis]], [[Fatty liver|hepatic steatosis]].
*Not recommended in patients with [[creatinine clearance]] <30 ml/min or Child–Pugh class C liver function, contraindicated with [[dofetilide]] or [[rifampin]], avoid divalent cations (Ca++, Mg++, Fe++), [[phenytoin]], [[carbamazepine]], and [[rifapentine]], and use with caution with [[metformin]].
 
=====Dolutegravir–3TC (50 mg/300 mg), once daily as single-tablet regimen=====
 
*Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), IRIS, lactic acidosis, hepatic steatosis.
 
*Do not use with [[lamivudine]] resistance (M184V or M184I mutation) or [[HBV infection]]; not recommended in patients with [[creatinine clearance]] <30 ml/min or Child–Pugh class B or C liver function; contraindicated with dofetilide; avoid divalent cations ([[Ca]]++, [[Magnesium|Mg]]++, [[Iron|Fe]]++), phenytoin, carbamazepine, and rifapentine; use with caution with metformin.
*Dolutegravir–3TC is not recommended for patients with rapid start of ART or for patients with chronic [[HBV infection]], [[Human Immunodeficiency Virus (HIV)|HIV]] RNA greater than 500,000 copies per milliliter, or a [[CD4]] cell count of less than 200 cells/mm3.
 
=====Raltegravir (600 mg), two tablets once daily=====
 
*Adverse effects: Gastrointestinal symptoms ([[Nausea and vomiting|nausea]], [[diarrhea]]), [[headache]], [[IRIS]], [[lactic acidosis]], [[Fatty liver|hepatic steatosis]].
*Not recommended in patients with [[creatinine clearance]] <30 ml/min or Child–Pugh class C liver function, contraindicated with [[dofetilide]] or [[rifampin]], avoid divalent cations (Ca++, Mg++, Fe++), [[phenytoin]], [[carbamazepine]], and [[rifapentine]], and use with caution with [[metformin]].
 
=====Plus TAF–FTC (25 mg/200 mg), once daily as single-tablet regimen=====
 
*Adverse effects: Gastrointestinal symptoms ([[Nausea and vomiting|nausea]], [[diarrhea]]), [[headache]], [[IRIS]], [[lactic acidosis]], [[Fatty liver|hepatic steatosis]].
*Not recommended in patients with [[creatinine clearance]] <30 ml/min or Child–Pugh class C liver function, contraindicated with [[dofetilide]] or [[rifampin]], avoid divalent cations (Ca++, Mg++, Fe++), [[phenytoin]], [[carbamazepine]], and [[rifapentine]], and use with caution with [[metformin]].
 
=====Plus TDF–FTC (300 mg/200 mg), once daily as single-tablet regimen=====
 
*Adverse effects: Gastrointestinal symptoms ([[Nausea and vomiting|nausea]], [[diarrhea]]), [[headache]], [[IRIS]], [[lactic acidosis]], [[Fatty liver|hepatic steatosis]].
*Not recommended in patients with [[creatinine clearance]] <30 ml/min or Child–Pugh class C liver function, contraindicated with [[dofetilide]] or [[rifampin]], avoid divalent cations ([[Ca]]++, [[Magnesium|Mg]]++, [[Iron|Fe]]++), [[phenytoin]], [[carbamazepine]], and [[rifapentine]], and use with caution with [[metformin]].
 
=====Plus TDF–3TC (300 mg/300 mg), Individual tablets each once daily=====
 
*Adverse effects: Gastrointestinal symptoms ([[Nausea and vomiting|nausea]], [[diarrhea]]), [[headache]], [[IRIS]], [[lactic acidosis]], [[Fatty liver|hepatic steatosis]].
*Not recommended in patients with [[creatinine clearance]] <30 ml/min or Child–Pugh class C [[Liver function tests|liver function]], contraindicated with [[dofetilide]] or [[rifampin]], avoid divalent cations (Ca++, Mg++, Fe++), [[phenytoin]], [[carbamazepine]], and [[rifapentine]], and use with caution with [[metformin]].
 
 
'''Abbreviations'''
 
FTC emtricitabine
 
TAF tenofovir alafenamide fumarate,
 
TDF tenofovir disoproxil fumarate,
 
3TC lamivudine.
 
 
 
<br />
===Treatment Failure===
{| style="border: 0px; font-size: 95%; margin: 3px; width: 500px;" align="center"
| valign="top" |
|+
! colspan="2" style="background: #4479BA; color:#FFF;  width: 220px;" |Definitions of Treatment Failure
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |Clinical Failure
| style="padding: 5px 5px; background: #F5F5F5;" |
*New or recurrent WHO stage 4 condition
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |CD4 Cell Failure
| style="padding: 5px 5px; background: #F5F5F5;" |
*Fall of CD4 count to pre-therapy baseline (or below), OR
*50% fall from the on-treatment peak value (if known), OR
*Persistent CD4 levels below 100 cells/mm3
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |Virological Failure
| style="padding: 5px 5px; background: #F5F5F5;" |
*Plasma viral load > 1 000 copies/ml
|-
 
| colspan="2" style="padding: 5px 5px; background: #F5F5F5;" |<small> Table adapted from WHO Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection<ref name="WHO HIV1"> {{cite web| url=http://apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf| title= WHO 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection }} </ref></small>
|}
 
{| style="border: 0px; font-size: 95%; margin: 3px; width: 900px;" align="center"
| valign="top" |
|+
! style="background: #4479BA; color:#FFF; width:150px" |Treatment Failure Criteria
! style="background: #4479BA; color:#FFF;" |[[AIDS classification|Stage 1]]
! style="background: #4479BA; color:#FFF;" |[[AIDS classification|Stage 2]]
! style="background: #4479BA; color:#FFF;" |[[AIDS classification|Stage 3]]
! style="background: #4479BA; color:#FFF;" |[[AIDS classification|Stage 4]]
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |CD4 cell failure
| style="padding: 5px 5px; background: #F5F5F5;width: 200px" |Not recommended to switch regimen. Repeat CD4 count in 3 months
| style="padding: 5px 5px; background: #F5F5F5;width: 200px" |Not recommended to switch regimen. Repeat CD4 count in 3 months
| style="padding: 5px 5px; background: #F5F5F5;width: 200px" |Consider switching to second-line regimen<sup>†</sup>
| style="padding: 5px 5px; background: #F5F5F5;width: 200px" |Recommend to switch to second-line regimen<sup>†</sup>
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |CD4 cell failure and viral load failure
| style="padding: 5px 5px; background: #F5F5F5;" |Consider second-line regimen<sup>†</sup>
| style="padding: 5px 5px; background: #F5F5F5;" |Consider second-line regimen<sup>†</sup>
| style="padding: 5px 5px; background: #F5F5F5;" |Recommended to switch to second-line regimen<sup>†</sup>
| style="padding: 5px 5px; background: #F5F5F5;" |Recommended to switch to second-line regimen<sup>†</sup>
|-
| colspan="5" style="padding: 5px 5px; background: #F5F5F5;" |<small> <sup>†</sup> Switching should not be done until the first regimen has been given sufficient time to succeed (at least 6 months). <br> Table adapted from WHO GUIDELINES ON ANTIRETROVIRAL THERAPY FOR HIV INFECTION IN ADULTS AND ADOLESCENTS <ref>{{cite web| url=http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf?ua=1| title= WHO GUIDELINES ON ANTIRETROVIRAL THERAPY FOR HIV INFECTION IN ADULTS AND ADOLESCENTS}} </ref></small>
|}


===Special Considerations===
===Special Considerations===
*HAART allows the stabilization of the patient’s symptoms and viremia, but it neither cures the patient of HIV, nor alleviates the symptoms, and high levels of HIV-1, often HAART resistant, return once treatment is stopped.<ref name=martinez>{{


cite journal
*HAART allows the stabilization of the patient’s symptoms and viremia, but it neither cures the patient of HIV, nor alleviates the symptoms, and high levels of HIV-1, often HAART resistant, return once treatment is stopped.<ref name="martinez">{{cite journal
  | author=Martinez-Picado J, DePasquale MP, Kartsonis N, et al| title=Antiretroviral resistance during successful therapy of human immunodeficiency virus type 1 infection | journal=Proc. Natl. Acad. Sci. U. S. A. | year=2000 | pages=10948&ndash;10953 | volume=97| issue=20 | pmid=11005867
  | author=Martinez-Picado J, DePasquale MP, Kartsonis N, et al| title=Antiretroviral resistance during successful therapy of human immunodeficiency virus type 1 infection | journal=Proc. Natl. Acad. Sci. U. S. A. | year=2000 | pages=10948&ndash;10953 | volume=97| issue=20 | pmid=11005867


}}</ref><ref name=Dybul>{{
}}</ref><ref name="Dybul">{{cite journal
 
cite journal
  | author=Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK; Panel on Clinical Practices for Treatment of HIV.
  | author=Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK; Panel on Clinical Practices for Treatment of HIV.
  | title=Guidelines for using antiretroviral agents among HIV-infected adults and adolescents
  | title=Guidelines for using antiretroviral agents among HIV-infected adults and adolescents
Line 385: Line 606:
  | pmid=12617573
  | pmid=12617573


}}</ref> Moreover, it would take more than the lifetime of an individual to be cleared of HIV infection using HAART.<ref name=blankson>{{
}}</ref>
 
*It would take more than the lifetime of an individual to be cleared of HIV infection using HAART.<ref name="blankson">{{cite journal
cite journal
  | author=Blankson JN, Persaud D, Siliciano RF | title=The challenge of viral reservoirs in HIV-1 infection | journal=Annu. Rev. Med. | year=2002 | pages=557&ndash;593 | volume=53 | issue= | pmid=11818490
  | author=Blankson JN, Persaud D, Siliciano RF | title=The challenge of viral reservoirs in HIV-1 infection | journal=Annu. Rev. Med. | year=2002 | pages=557&ndash;593 | volume=53 | issue= | pmid=11818490


}}</ref> Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality.<ref name=Pallelal>{{
}}</ref>
 
*Many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality.<ref name="Pallelal">{{cite journal
cite journal
  | author=Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD | title=Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection | journal=N. Engl. J. Med. | year=1998 |pages=853&ndash;860 | volume=338 | issue=13 | pmid=9516219
  | author=Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD | title=Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection | journal=N. Engl. J. Med. | year=1998 |pages=853&ndash;860 | volume=338 | issue=13 | pmid=9516219


}}</ref><ref name=Wood>{{
}}</ref><ref name="Wood">{{cite journal
 
cite journal
  | author=Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS
  | author=Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS
  | title=Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy?
  | title=Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy?
Line 403: Line 620:
  | pmid=12646794
  | pmid=12646794


}}</ref><ref name=Chene>{{
}}</ref><ref name="Chene">{{cite journal
 
cite journal
  | author=Chene G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, Dabis F, Lundgren J, D'Arminio Monforte A, de Wolf F, Hogg R, Reiss P, Justice A, Leport C, Staszewski S, Gill J, Fatkenheuer G, Egger ME and the Antiretroviral Therapy Cohort Collaboration
  | author=Chene G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, Dabis F, Lundgren J, D'Arminio Monforte A, de Wolf F, Hogg R, Reiss P, Justice A, Leport C, Staszewski S, Gill J, Fatkenheuer G, Egger ME and the Antiretroviral Therapy Cohort Collaboration
  | title=Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies
  | title=Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies
Line 412: Line 627:


}}</ref>
}}</ref>
===HIV in Children===
===HIV in Children===


Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations are more aggressive for children than for adults.<ref name=2005dhhsHivChildren>{{
Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations are more aggressive for children than for adults.<ref name="2005dhhsHivChildren">{{cite web
 
cite web
  | publisher=Department of Health and Human Services Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children
  | publisher=Department of Health and Human Services Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children
  | date=2005-11-03
  | date=2005-11-03
Line 428: Line 642:
==Treatment Adherence==
==Treatment Adherence==


Adherence is taking the correct dose of each anti-HIV medication at the correct time and exactly as prescribed. Adherence is very important for successful HIV treatment. The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, [[psychiatric]] disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues, along with side effects that create intentional non-adherence, also has a weighty impact.<ref name=Nieuwkerk>{{
Adherence is taking the correct dose of each anti-HIV medication at the correct time and exactly as prescribed. Adherence is very important for successful HIV treatment. The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, [[psychiatric]] disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues, along with side effects that create intentional non-adherence, also has a weighty impact.<ref name="Nieuwkerk">{{cite journal
cite journal
  | author=Nieuwkerk P, Sprangers M, Burger D, Hoetelmans RM, Hugen PW, Danner SA, van Der Ende ME, Schneider MM, Schrey G, Meenhorst PL, Sprenger HG, Kauffmann RH, Jambroes M, Chesney MA, de Wolf F, Lange JM and the ATHENA Project | title=Limited Patient Adherence to Highly Active Antiretroviral Therapy for HIV-1 Infection in an Observational Cohort Study | journal=Arch. Intern. Med. | year=2001 | pages=1962&ndash;1968 | volume=161 | issue=16 | pmid=11525698
  | author=Nieuwkerk P, Sprangers M, Burger D, Hoetelmans RM, Hugen PW, Danner SA, van Der Ende ME, Schneider MM, Schrey G, Meenhorst PL, Sprenger HG, Kauffmann RH, Jambroes M, Chesney MA, de Wolf F, Lange JM and the ATHENA Project | title=Limited Patient Adherence to Highly Active Antiretroviral Therapy for HIV-1 Infection in an Observational Cohort Study | journal=Arch. Intern. Med. | year=2001 | pages=1962&ndash;1968 | volume=161 | issue=16 | pmid=11525698


}}</ref><ref name=Kleeberger>{{
}}</ref><ref name="Kleeberger">{{cite journal
 
cite journal
  | author=Kleeberger C, Phair J, Strathdee S, Detels R, Kingsley L, Jacobson LP | title=Determinants of Heterogeneous Adherence to HIV-Antiretroviral Therapies in the Multicenter AIDS Cohort Study| journal=J. Acquir. Immune Defic. Syndr. | year=2001 | pages=82&ndash;92 | volume=26 | issue=1 | pmid=11176272
  | author=Kleeberger C, Phair J, Strathdee S, Detels R, Kingsley L, Jacobson LP | title=Determinants of Heterogeneous Adherence to HIV-Antiretroviral Therapies in the Multicenter AIDS Cohort Study| journal=J. Acquir. Immune Defic. Syndr. | year=2001 | pages=82&ndash;92 | volume=26 | issue=1 | pmid=11176272


}}</ref><ref name=heath>{{
}}</ref><ref name="heath">{{cite journal
 
cite journal
  | author=Heath KV, Singer J, O'Shaughnessy MV, Montaner JS, Hogg RS | title=Intentional Nonadherence Due to Adverse Symptoms Associated With Antiretroviral Therapy | journal=J. Acquir. Immune Defic. Syndr. | year=2002 | pages=211&ndash;217 | volume=31 | issue=2 | pmid=12394800
  | author=Heath KV, Singer J, O'Shaughnessy MV, Montaner JS, Hogg RS | title=Intentional Nonadherence Due to Adverse Symptoms Associated With Antiretroviral Therapy | journal=J. Acquir. Immune Defic. Syndr. | year=2002 | pages=211&ndash;217 | volume=31 | issue=2 | pmid=12394800


Line 445: Line 654:
===Difficulty in Adherence===
===Difficulty in Adherence===
There are several reasons why adhering to an HIV treatment regimen can be diicult. Most treatment regimens involve taking several pills every day with or without food, or before or after other medications. Other factors that can make treatment adherence difficult include:  
There are several reasons why adhering to an HIV treatment regimen can be diicult. Most treatment regimens involve taking several pills every day with or without food, or before or after other medications. Other factors that can make treatment adherence difficult include:  
* Difficulty taking medications (such as trouble swallowing pills).  
 
* Side effects from medications (for example, [[fatigue]] or [[diarrhea]]).  
*Difficulty taking medications (such as trouble swallowing pills).
* Daily schedule issues (including a busy schedule, shift work, or travel away from home) .
*Side effects from medications (for example, [[fatigue]] or [[diarrhea]]).
* Being sick or depressed .
*Daily schedule issues (including a busy schedule, shift work, or travel away from home) .
* Alcohol or drug abuse.
*Being sick or depressed .
*Alcohol or drug abuse.


===Importance of Adherence===
===Importance of Adherence===
Adherence effects the success of HIV treatment in two ways:  
Adherence effects the success of HIV treatment in two ways:  
*Good adherence to an HIV treatment regimen helps anti-HIV medications work effectively to reduce the [[viral load]]. Skipping medications, even occasionally, gives HIV to multiply rapidly. Preventing the virus from multiplying is the best way to stay healthy.  
 
*Good adherence to an HIV treatment regimen also helps prevent [[drug resistance]]. One or more anti-HIV medications in a treatment regimen can become ineffective as a result of drug resistance.  
*Good adherence to an HIV treatment regimen helps anti-HIV medications work effectively to reduce the [[viral load]]. Skipping medications, even occasionally, gives HIV to multiply rapidly. Preventing the virus from multiplying is the best way to stay healthy.
*Good adherence to an HIV treatment regimen also helps prevent [[drug resistance]]. One or more anti-HIV medications in a treatment regimen can become ineffective as a result of drug resistance.


Skipping medications makes it easier for drug resistance to develop. HIV can develop resistance to the anti-HIV medications in a person’s current regimen or to other, similar anti-HIV medications not yet taken, limiting options for successful HIV treatment. And drug-resistant strains of HIV can be transmitted to others, too. Although there are many different anti-HIV medications and treatment regimens, studies show that a person’s first regimen offers the best chance for long-term treatment success. Adhering to the regimen from the start will help ensure that the HIV treatment is successful.
Skipping medications makes it easier for drug resistance to develop. HIV can develop resistance to the anti-HIV medications in a person’s current regimen or to other, similar anti-HIV medications not yet taken, limiting options for successful HIV treatment. And drug-resistant strains of HIV can be transmitted to others, too. Although there are many different anti-HIV medications and treatment regimens, studies show that a person’s first regimen offers the best chance for long-term treatment success. Adhering to the regimen from the start will help ensure that the HIV treatment is successful.
Line 462: Line 673:


Viral load reduction may be more rapid in following patients:<ref name="pmid11920314">{{cite journal |author=Gottlieb GS, Sow PS, Hawes SE, Ndoye I, Redman M, Coll-Seck AM, Faye-Niang MA, Diop A, Kuypers JM, Critchlow CW, Respess R, Mullins JI, Kiviat NB |title=Equal plasma viral loads predict a similar rate of CD4+ T cell decline in human immunodeficiency virus (HIV) type 1- and HIV-2-infected individuals from Senegal, West Africa |journal=J. Infect. Dis. |volume=185 |issue=7 |pages=905–14 |year=2002 |month=April |pmid=11920314 |doi=10.1086/339295 |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11920314 |accessdate=2012-02-19}}</ref>
Viral load reduction may be more rapid in following patients:<ref name="pmid11920314">{{cite journal |author=Gottlieb GS, Sow PS, Hawes SE, Ndoye I, Redman M, Coll-Seck AM, Faye-Niang MA, Diop A, Kuypers JM, Critchlow CW, Respess R, Mullins JI, Kiviat NB |title=Equal plasma viral loads predict a similar rate of CD4+ T cell decline in human immunodeficiency virus (HIV) type 1- and HIV-2-infected individuals from Senegal, West Africa |journal=J. Infect. Dis. |volume=185 |issue=7 |pages=905–14 |year=2002 |month=April |pmid=11920314 |doi=10.1086/339295 |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11920314 |accessdate=2012-02-19}}</ref>
* Having high CD4 cell count.
* Having lower levels of baseline viremia.
* In treatment-naive patients.


{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px; float:center" align=center
*Having high CD4 cell count.
|valign=top|
*Having lower levels of baseline viremia.
*In treatment-naive patients.
 
{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px; float:center" align="center"
| valign="top" |
|+
|+
! style="background: #4479BA; color:#FFF;  width: 200px;" |''' Time '''
! style="background: #4479BA; color:#FFF;  width: 200px;" |''' Time '''
! style="background: #4479BA; color:#FFF;  width: 200px;" |'''Expected decrease in Viral load'''
! style="background: #4479BA; color:#FFF;  width: 200px;" |'''Expected decrease in Viral load'''
|-
|-
| style="padding: 5px 5px; background: #DCDCDC"| 1 week
| style="padding: 5px 5px; background: #DCDCDC" |1 week
| style="padding: 5px 5px; background: #F5F5F5;" | Decrease by 0.75 to 1 log10 copies/mL
| style="padding: 5px 5px; background: #F5F5F5;" |Decrease by 0.75 to 1 log10 copies/mL
|-
|-
| style="padding: 5px 5px; background: #DCDCDC"| 1 month  
| style="padding: 5px 5px; background: #DCDCDC" |1 month
| style="padding: 5px 5px; background: #F5F5F5;" | Decrease by 1.5 to 2 log10 copies/mL to <5000 copies/mL .
| style="padding: 5px 5px; background: #F5F5F5;" |Decrease by 1.5 to 2 log10 copies/mL to <5000 copies/mL .
|-
|-
| style="padding: 5px 5px; background: #DCDCDC"| 2 to 4 months.  
| style="padding: 5px 5px; background: #DCDCDC" |2 to 4 months.
| style="padding: 5px 5px; background: #F5F5F5;" | <500 copies/mL  
| style="padding: 5px 5px; background: #F5F5F5;" |<500 copies/mL
|-
|-
| style="padding: 5px 5px; background: #DCDCDC"|4 to 6 months.
| style="padding: 5px 5px; background: #DCDCDC" |4 to 6 months.
| style="padding: 5px 5px; background: #F5F5F5;" | < 50 copies/mL.
| style="padding: 5px 5px; background: #F5F5F5;" |< 50 copies/mL.
|}
|}


Line 491: Line 703:


Two main causes of the failure are:
Two main causes of the failure are:
#[[Drug resistance]].
#[[Drug resistance]].
#Failure of the drugs to reach the target site.
#Failure of the drugs to reach the target site.
Line 498: Line 711:


Department of Health and Human Services (DHHS) have suggested that viral blips do not require intervention with a new regimen unless the viral load is sustained at >200 copies/mL.
Department of Health and Human Services (DHHS) have suggested that viral blips do not require intervention with a new regimen unless the viral load is sustained at >200 copies/mL.
<!---
<!---
===NIH Recommendations:Treatment-Experienced Patient===
===NIH Recommendations:Treatment-Experienced Patient===
Line 546: Line 758:
===Monitoring CD4 and Viral Load===
===Monitoring CD4 and Viral Load===


{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px;" align=center
{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px;" align="center"
|valign=top|
| valign="top" |
|+
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Scenario}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Scenario}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|CD4 Monitoring}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|CD4 Monitoring}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Viral Load Monitoring}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Viral Load Monitoring}}
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | Before receiving ART
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Before receiving ART
| style="padding: 5px 5px; background: #F5F5F5;" | Yes
| style="padding: 5px 5px; background: #F5F5F5;" |Yes
| style="padding: 5px 5px; background: #F5F5F5;" | Yes
| style="padding: 5px 5px; background: #F5F5F5;" |Yes
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | While receiving ART
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |While receiving ART
| style="padding: 5px 5px; background: #F5F5F5;" | 3 month after initiation of ART
| style="padding: 5px 5px; background: #F5F5F5;" |3 month after initiation of ART
| style="padding: 5px 5px; background: #F5F5F5;" | 2-4 weeks after initiation of ART, then every 4-8 weeks
| style="padding: 5px 5px; background: #F5F5F5;" |2-4 weeks after initiation of ART, then every 4-8 weeks
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | ART regimen is modified due to drug toxicity
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |ART regimen is modified due to drug toxicity
| style="padding: 5px 5px; background: #F5F5F5;" | Will depend on previous CD4 counts
| style="padding: 5px 5px; background: #F5F5F5;" |Will depend on previous CD4 counts
| style="padding: 5px 5px; background: #F5F5F5;" | 4-8 weeks after modification of regimen
| style="padding: 5px 5px; background: #F5F5F5;" |4-8 weeks after modification of regimen
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |ART regimen is modified due to virologic failure
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |ART regimen is modified due to virologic failure
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3-6 months
| style="padding: 5px 5px; background: #F5F5F5;" |Every 3-6 months
| style="padding: 5px 5px; background: #F5F5F5;" | 2-4 weeks after initiation of ART, then every 4-8 weeks
| style="padding: 5px 5px; background: #F5F5F5;" |2-4 weeks after initiation of ART, then every 4-8 weeks
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | During the first 2 years of ART
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |During the first 2 years of ART
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3-6 months
| style="padding: 5px 5px; background: #F5F5F5;" |Every 3-6 months
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3-4 months
| style="padding: 5px 5px; background: #F5F5F5;" |Every 3-4 months
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |While on ART with detectable viremia (>200 copies/mL)
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |While on ART with detectable viremia (>200 copies/mL)
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3-6 months
| style="padding: 5px 5px; background: #F5F5F5;" |Every 3-6 months
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 months
| style="padding: 5px 5px; background: #F5F5F5;" |Every 3 months
|-
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | Change in clinical status <br><small> (new HIV clinical symptom or initiation of interferon, chronic systemic corticosteroids, or antineoplastic therapy)</small>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Change in clinical status <br><small> (new HIV clinical symptom or initiation of interferon, chronic systemic corticosteroids, or antineoplastic therapy)</small>
| style="padding: 5px 5px; background: #F5F5F5;" | Will depend on the clinical scenario  
| style="padding: 5px 5px; background: #F5F5F5;" |Will depend on the clinical scenario
| style="padding: 5px 5px; background: #F5F5F5;" | Every 3 months
| style="padding: 5px 5px; background: #F5F5F5;" |Every 3 months
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left colspan=3| <small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
| colspan="3" style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
|}
|}


===Other Laboratory Monitoring===
===Other Laboratory Monitoring===
{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px;" align=center
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | At HIV diagnosis
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |At HIV diagnosis
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | At initiation of ART
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |At initiation of ART
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | After 2-8 weeks after ART initiation
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |After 2-8 weeks after ART initiation
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*HbA1c or fasting glucose (if abnormal previously)
*HbA1c or fasting glucose (if abnormal previously)
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align=left colspan=3| <small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
| colspan="3" style="font-size: 90%; padding: 0 5px; background: #F5F5F5;" align="left" |<small>Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. <ref name="AIDSinfo"> {{cite web| url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/0| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014}} </ref></small>
|}
|}
==Treatment Regimen==
*1. '''Antiretroviral regimen options for treatment-naive patients<ref name="AIDSinfoNIH">{{cite web | title = AIDSinfoNIH | url =https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/11/what-to-start }}</ref><ref name="JAMA">{{cite journal |last1=Gunthardt |first1=HF |last2= Saag |first2=Michael |last3=Benson |first3= C |date=Jul 21, 2016 |year=2016 |title=Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society–USA Panel |url=http://jamanetwork.com/journals/jama/fullarticle/2533073 |journal= JAMA |publisher= The JAMA Network |publication-date=2016 |volume=316 |issue=2 |pages=191-210 |doi=10.1001/jama.2016.8900 |pmc=PMC5012643 |pmid=27404187  }}</ref>'''
:*1.1. '''Integrase strand transfer inhibitor-based regimens'''
::*Preferred regimen (1): [[Dolutegravir]] 50 mg PO qd {{and}} [[Abacavir]] 600 mg-[[Lamivudine]] 300 mg PO qd in patients who are HLA-B*5701-negative
::*Preferred regimen (2): [[Dolutegravir]] 50 mg PO qd {{and}} [[Tenofovir]] 300 mg-[[Emtricitabine]] 200 mg PO qd
::*Preferred regimen (3): [[Elvitegravir]] 150 mg-[[Cobicistat]] 150 mg-[[Tenofovir]] 300 mg-[[Emtricitabine]] 200 mg PO qd in patients with estimated CrCl ≥ 70 mL/min/1.73
::*Preferred regimen (4): [[Raltegravir]] 400 mg PO bid {{and}} [[Tenofovir]] 300 mg-[[Emtricitabine]] 200 mg PO qd
::*Alternative regimen (1): [[Efavirenz]] 600 mg PO qd {{or}} [[Tenofovir]] 300 mg-[[Emtricitabine]] 200 mg PO qd
::*Alternative regimen (2): [[Rilpivirine]] 25 mg PO qd {{and}} ([[Tenofovir]] 300 mg PO qd {{or}} [[Emtricitabine]] 200 mg PO qd) for patients with CD4 count >200 cells/microL
::*Alternative regimen (3): [[Raltegravir]] 400 mg PO bid  {{and}} ([[Abacavir]] 600 mg PO qd {{or}} [[Lamivudine]] 300 mg PO qd) in patients who are HLA-B*5701-negative
:*1.2. '''Protease inhibitor-based regimen'''
::*Preferred regimen: [[Darunavir]] 800 mg-[[Ritonavir]] 100 mg PO qd {{and}} [[Tenofovir]] 300 mg-[[Emtricitabine]] 200 mg PO qd
::*Alternative regimen (1): [[Atazanavir]] 300 mg-[[Cobicistat]] 150 mg PO qd {{and}} [[Tenofovir]] disoproxil fumarate 300 mg-[[Emtricitabine]] 200 mg PO qd only for patients with pre-treatment estimated CrCl ≥70 mL/min
::*Alternative regimen (2): [[Atazanavir]] 300 mg-[[Ritonavir]] 100 mg PO qd {{and}} [[Tenofovir]] 300 mg-[[Emtricitabine]] 200 mg PO qd
::*Alternative regimen (3): ([[Darunavir]] 800 mg-[[Cobicistat]] 150 mg PO qd {{or}} [[Darunavir]] 800 mg-[[Ritonavir]] 100 mg PO qd) {{and}} [[Abacavir]] 600 mg-[[Lamivudine]] 300 mg PO qd only for patients who are HLA-B*5701 negative
::*Alternative regimen (4): [[Darunavir]] 800 mg-[[Cobicistat]] 150 mg PO qd {{and}} [[Tenofovir]] disoproxil fumarate 300 mg-[[Emtricitabine]] 200 mg PO qd only for patients with pre-treatment estimated CrCl ≥70 mL/min
::*Alternative regimen (5): [[Atazanavir]] 300 mg-[[Ritonavir]] 100 mg PO qd {{and}} [[Abacavir]] 600 mg-[[Lamivudine]] 300 mg PO qd in patients who are HLA-B*5701-negative and with pre-treatment HIV RNA <100,000 copies/mL
::*Alternative regimen (6): [[Lopinavir]] 400 mg-[[Ritonavir]] 100 mg PO qd or bid {{and}} [[Abacavir]] 600 mg-[[Lamivudine]] 300 mg PO qd only for patients who are HLA-B*5701 negative
::*Alternative regimen (7): [[Lopinavir]] 400 mg-[[Ritonavir]] 100 mg PO qd or bid {{and}} [[Tenofovir]] disoproxil fumarate 300 mg-[[Emtricitabine]] 200 mg PO qd
:*1.3. '''A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen'''
::*Alternative regimen (1): [[Efavirenz]] 600 mg-[[Tenofovir]] 300 mg-[[Emtricitabine]] 200 mg PO qd
::*Alternative regimen (2): [[Rilpivirine]] 25 mg-[[Tenofovir]] 300 mg-[[Emtricitabine]] 200 mg PO qd
:*1.4. '''Other regimen options'''
::*1.4.1. '''A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen'''
:::*Preferred regimen (1):  [[Efavirenz]] 600 mg PO qd {{and}} [[Abacavir]] 600 mg-[[Lamivudine]] 300 mg PO qd only for patients who are HLA-B*5701 negative and with pre-treatment HIV RNA <100,000 copies/mL.
::*1.4.2. '''Other regimens when tenofovir or abacavir cannot be used'''
:::*Preferred regimen (1): [[Darunavir]] 800 mg-[[Ritonavir]] 100 mg PO qd {{and}} [[Raltegravir]] 400 mg PO qd only for patients with pre-treatment HIV RNA <100,000 copies/mL and CD4 cell count >200 cells/mm3.
:::*Preferred regimen (2): [[Lopinavir]] 400 mg-[[Ritonavir]] 100 mg PO bid {{and}} [[Lamivudine]] 300 mg PO bid
:*1.5. '''Pediatric doses<ref name="AIDSinfoNIH" pediatric="" doses="">{{cite web | title = AIDSinfoNIH pediatric doses | url =https://aidsinfo.nih.gov/contentfiles/lvguidelines/PediatricGuidelines.pdf }}</ref>'''
::*[[Abacavir]] 300 mg PO bid
::*[[Lamivudine]] 4 mg/kg/dose PO bid; maximum 150 mg PO bid
::*[[Stavudine]] 1 mg/kg/dose PO bid
::*[[Tenofovir]] 8 mg/kg/dose PO bid
::*[[Zidovudine]] 180-240 mg/m<sup>2</sup>/dose PO bid or 160 mg/m<sup>2</sup>/dose PO tid (range 90 mg/m<sup>2</sup>/dose-180 mg/m<sup>2</sup>/dose)
::*[[Lopinavir]] 400 mg PO bid
::*[[Nelfinavir]] 50 mg/kg/dose PO bid
::*[[Raltegravir]] 300 mg PO bid
::*[[Didanosine]]
:::*20 to < 25 kg: 200 mg PO qd
:::*25 to < 60 kg: 250 mg PO qd
:::*≥60 kg: 400 mg PO qd
::*[[Efavirenz]]
:::*10 to < 15 kg: 200 mg PO qd
:::*15 to <20 kg: 250 mg PO qd
:::*20 to < 25 kg: 300 mg PO qd
:::*25 to < 32.5 kg: 350 mg PO qd
:::*32.5 to <40 kg: 400 mg PO qd
:::*≥ 40 kg: 600 mg PO qd
::*[[Nevirapine]] maximum 200 mg per dose
:::*Between 1 day and 8 years: 200 mg/m<sup>2</sup>/dose PO qd for 14 days, then 200 mg/m<sup>2</sup>/dose PO bid
:::*8 years and above: 120-150 mg/m<sup>2</sup>/dose PO qd for 14 days, then 120-150 mg/m<sup>2</sup>/dose PO bid
::*Note (1): Anti retroviral therapy for treatment naive patients is a life long therapy.
::*Note (2): [[Tenofovir]] disoproxil fumarate should be avoided in patients with a creatinine clearance <50 mL/min.
::*Note (3): [[Rilpivirine]] should be used in patients with a CD4 cell count >200 copies/mL and should not be used with proton pump inhibitors.
::*Note (4): [[Efavirenz]] should not be used in pregnant women.
 
*2. '''Pre-exposure prophylaxis (PrEP)<ref name="CDC" pre-exposure="" prophylaxis="">{{cite web | title = CDC Pre-Exposure Prophylaxis | url =http://www.cdc.gov/hiv/pdf/PrEP_fact_sheet_final.pdf }}</ref>'''
:*Preferred regimen: [[Tenofovir]] disoproxil fumarate 300 mg-[[Emtricitabine]] 200 mg PO qd for ≤90-days
:*Note (1): People with high risk behavior such as men who have sex with men, intravenous drug abusers, HIV-positive sexual partner, recent bacterial STI, high number of sex partners, history of inconsistent or no condom use, commercial sex work, people in high-prevalence area or network are advised to take pre-exposure prophylaxis of drugs.
:*Note (2): Follow-up visits at least every 3 months to provide the following: HIV test, medication adherence counseling, behavioral risk reduction support, side effect assessment, STI symptom assessment, pregnancy testing.
:*Note (3): At 3 months and every 6 months thereafter, assess renal function.
:*Note (4): Every 6 months, test for bacterial STIs.
*3. '''Post- exposure prophylaxis<ref name="WHO" post="" exposure="" prophylaxis="">{{cite web | title = WHO postexposureprophylaxis | url =http://www.who.int/hiv/topics/prophylaxis/en/ }}</ref>'''
:*Preferred regimen: [[Raltegravir]] 400 mg PO bid {{and}} [[Tenofovir]] disoproxil fumarate 300 mg-[[Emtricitabine]] 200 mg PO qd
:*Preferred basic regimen for low-risk exposures (Eg: mucus membrane):
:**[[Zidovudine]] 100 mg PO qd {{and}} [[Lamivudine]] 300 mg PO qd
:**[[Zidovudine]] 100 mg PO qd {{and}} [[Emtricitabine]] 200 mg PO qd
:**[[Tenofovir]] 300 mg PO qd {{and}} [[Lamivudine]] 300 mg PO qd
:**[[Tenofovir]] 300 mg PO qd {{and}} [[Emtricitabine]] 200 mg PO qd
:*Preferred expanded regimen for high-risk exposure (Eg: percutaneous needle stick)
:**[[Zidovudine]] 100 mg PO qd {{and}} [[Lamivudine]] 300 mg PO qd {{and}} [[Lopinavir]] 400 mg-[[Ritonavir]] 100 mg PO qd
:**[[Zidovudine]] 100 mg PO qd {{and}} [[Emtricitabine]] 200 mg PO qd {{and}} [[Lopinavir]] 400 mg-[[Ritonavir]] 100 mg PO qd
:**[[Tenofovir]] 300 mg PO qd {{and}} [[Lamivudine]] 300 mg PO qd {{and}} [[Lopinavir]] 400 mg-[[Ritonavir]] 100 mg PO qd
:**[[Tenofovir]] 300 mg PO qd {{and}} [[Emtricitabine]] 200 mg PO qd{{and}} [[Lopinavir]] 400 mg-[[Ritonavir]] 100 mg PO qd
:*Note: Ideally therapy should be started within hours of exposure and continued for 28 days.
*4. '''Perinatal antiretroviral regimen<ref name="AIDSinfoNIH" intrapartum="" car="">{{cite web | title = AIDSinfoNIH intrapartum care | url =https://aidsinfo.nih.gov/guidelines/html/3/perinatal-guidelines/180/intrapartum-antiretroviral-therapy-prophylaxis }}</ref>'''
:*4.1. '''Antepartum'''
::*4.1.1. '''Protease inhibitor-based regimen'''
:::*Preferred regimen: ([[Tenofovir]] 300 mg-[[Emtricitabine]] 200 mg PO qd (fixed dose combination) {{or}} [[Tenofovir]] 300 mg-[[Lamivudine]] 300 mg PO qd {{or}} [[Abacavir]] 600 mg-[[Lamivudine]] 300 mg PO qd {{or}} [[Zidovudine]] 100 mg-[[Lamivudine]] 300 mg PO qd) {{and}} ([[Atazanavir]] 300 mg-[[Ritonavir]] 100 mg PO qd {{or}} [[Lopinavir]] 400 mg-[[Ritonavir]] 100 mg PO qd)
::*4.1.2. '''A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen:'''
:::*Preferred regimen (1): [[Efavirenz]] 600 mg-[[Tenofovir]] 300 mg-[[Emtricitabine]] 200 mg (fixed dose combination) PO qd
:::*Preferred regimen (2): [[Efavirenz]] 600 mg-[[Tenofovir]] 300 mg-[[Lamivudine]] 300 mg PO qd
:::*Alternative regimen: ([[Abacavir]] 600 mg-[[Lamivudine]] 300 mg PO qd {{or}} [[Zidovudine]] 100 mg-[[Lamivudine]] 300 mg PO qd) {{and}} [[Efavirenz]] 600 mg PO qd
:*4.2. '''Intrapartum'''
::*Note (1): HIV RNA <1000 copies/mL and good adherance-Continue the regimen during delivery or cessarean section.
::*Note (2): HIV RNA >1000 copies/mL near delivery, possible poor adherence, or unknown HIV RNA levels- Intravenous [[Zidovudine]] 2 mg/kg IV over 1 hr should be given three hours before cesarean section or delivery and then 1 mg/kg/hr IV continuous infusion until umbilical cord clamping.
:*4.3. '''Postpartum'''
::*Note: Initiate anti retroviral therapy (ART) and continue after delivery and cessation of breastfeeding.
*5. '''Infant antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV<ref name="AIDSinfoNIH" postpartum="" care="">{{cite web | title = AIDSinfoNIH postpartumcare | url =https://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf }}</ref>'''
:*5.1 '''Prophylaxis for HIV-exposed infants of women who received antepartum antiretroviral prophylaxis'''
::*Preferred regimen: [[Zidovudine]] (ZDV) 100 mg PO given at birth and continued till six weeks
::*Note (1): Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
::*Note (2): ≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
::*Note (3): ≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
::*Note (4): <30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.
:*5.2. '''Prophylaxis for HIV-exposed infants of women who received no antepartum antiretroviral prophylaxis'''
:::[[Nevirapine]]
:::*Dose based on birth weight, initiated as soon after birth as possible.
:::*Birth weight 1.5 to 2 kg: 8 mg/dose orally.
:::*Birth weight >2 kg: 12 mg/dose orally.
:::{{and}}
:::[[Zidovudine]] (ZDV)
:::*Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
::::*≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
::::*≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
::::*<30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.
:::*Note (1): Three doses in the first week of life.
:::*Note (2): First dose within 48 hours of birth (birth to 48 hrs).
:::*Note (3): Second dose 48 hours after first.
:::*Note (4): Third dose 96 hours after second.
===Primary Prophylaxis against Opportunistic Infections in Persons with HIV Infection<ref name="pmid340776452">{{cite journal| author=Saag MS| title=HIV Infection - Screening, Diagnosis, and Treatment. | journal=N Engl J Med | year= 2021 | volume= 384 | issue= 22 | pages= 2131-2143 | pmid=34077645 | doi=10.1056/NEJMcp1915826 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34077645  }}</ref>===
====Prophylaxis against [[Pneumocystis jirovecii pneumonia|Pneumocystis jirovecii]]====
*Indications: [[CD4+ cell|CD4]] count <200 cells/mm3 or [[thrush]]
*Drugs used:
**Trimethoprim–sulfamethoxazole one double-strength tablet (160 mg of [[trimethoprim]] and 800 mg of sulfamethoxazole) daily or 3 times/week
**[[Dapsone]] 100 mg, orally once daily
**[[Pentamidine]] 300 mg, aerosolized through [[nebulizer]] monthly
**[[Atovaquone]] 1500 mg, orally (liquid suspension) daily
====Prophylaxis against [[Cryptococcosis|cryptococcus]]====
*Indications: CD4 count <100 cells/mm3 and positive serum [[Cryptococcosis|cryptococcal]] antigen
*Drug used: [[fluconazole]] 200 mg, orally once daily
====Prophylaxis against [[histoplasmosis]]====
*Indications: CD4 count <150 cells/mm3 in areas where [[histoplasmosis]] is endemic
*Drug used: [[itraconazole]] 200 mg, orally once daily
==== Prophylaxis against [[Mycobacterium avium complex]] ====
It is no longer recommended in patient with rapid initiation of [[ART]]
===Management of HIV-patients===
The 2021 CDC STD guidelines recommend the following steps to be taken with every patient diagnosed with HIV:<ref name="pmid34292926">{{cite journal| author=Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I | display-authors=etal| title=Sexually Transmitted Infections Treatment Guidelines, 2021. | journal=MMWR Recomm Rep | year= 2021 | volume= 70 | issue= 4 | pages= 1-187 | pmid=34292926 | doi=10.15585/mmwr.rr7004a1 | pmc=8344968 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34292926  }} </ref>
*Link persons with [[HIV]] infection to care and start them on [[ART]] as soon as possible.
*Report cases (in accordance with local requirements) to [[public health]] and initiate partner services.
*Provide [[prevention]] [[counseling]] to persons with diagnosed [[HIV]] infection.
*Ensure all persons with [[HIV]] infection are informed that if they achieve and maintain a suppressed [[viral load]], they have effectively no risk for transmitting HIV. Stress that a suppressed viral load is not a substitute for [[condoms]] and [[behavioral modifications]] because [[ART]] does not protect persons with HIV against other [[STI]]s.
*Provide additional counseling, either on-site or through referral, about the psychosocial and medical implications of having HIV infection.
*Assess the need for immediate [[medical care]] and [[psychosocial support]].
*Link persons with diagnosed [[HIV]] infection to services provided by health care personnel experienced in managing [[HIV]] infection. Additional services that might be needed include substance misuse counseling and treatment, treatment for [[mental health]] disorders or [[emotional distress]], reproductive counseling, risk-reduction [[counseling]], and case management. Providers should [[follow up]] to ensure that patients have received services for any identified needs.
*Persons with [[HIV]] infection should be educated about the importance of ongoing medical care and what to expect from these services.


==References==
==References==
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[[Category:Disease]]
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]; Ammu Susheela, M.D. [3]; Tarek Nafee, M.D. [4]

Overview

The primary goal of antiretroviral therapy (ART) is to reduce HIV-associated morbidity and mortality. This goal is best accomplished by using highly-active ART to maximally inhibit HIV replication, as defined by achievement and maintenance of plasma HIV RNA (viral load) below detectable levels, restoration of normal CD4 cell count, and prevention of transmission of the disease. Major classes of agents used in the treatment of HIV are: Non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), fusion inhibitors, CCR5 antagonists, and integrase inhibitors. All regimens are combinations of at least 3 agents, preferably with 2 NRTIs. Durable viral suppression improves immune function and quality of life, lowers the risk of both AIDS-defining and non-AIDS-defining complications, and prolongs life. Based on emerging evidence, additional benefits of ART include a reduction in HIV-associated inflammation and its associated complications.

Medical Therapy

Anti-HIV medications (also called antiretrovirals) are grouped into six drug classes according to their mechanism of action. The six classes are as follows:

  1. Non-nucleoside reverse transcriptase inhibitors (NNRTIs).
  2. Nucleoside reverse transcriptase inhibitors (NRTIs).
  3. Protease inhibitors (PIs).
  4. Fusion inhibitors.
  5. CCR5 antagonists.
  6. Integrase inhibitors.

Multidrug regimen has proved to be very beneficial because of reduction in progression to AIDS, opportunistic infections, rate of hospitalizations and deaths. [1]

Goals of Therapy

  • Durable suppression of HIV viral load ( to <50 cells/mL ).
  • Restoration of normal CD4 cell count.
  • Prevention of transmission of the disease.
  • Prevention of building of drug resistance.
  • Improvement in quality of life of the patient.

Uncontrolled viremia causes inflammation and immune activation, which has an overall effect on cardiovascular, renal and hepatic systems. Controlling viremia also controls these effects.

Anti Retroviral Therapy (ART)

  • Current optimal HAART options consist of drug combinations consisting of at least three drugs belonging to at least two classes of antiretroviral agents.
  • Typical regimens consist of:
  • In treatment-naive patients, four drug regimen is not found to be more efficacious than three-drug regimens and is associated with more adverse events.[2][3]

Anti Retroviral Regimens

WHO Recommendations in Adults

▸ Click on the following categories to expand treatment regimens.

ARV Regimens

  ▸  First-Line Regimens

  ▸  Second-Line Regimens

First-line Regimen
Preferred Regimen
Emtricitabine (FTC)
OR
Lamivudine (3TC)
PLUS
Tenofovir (TDF)
PLUS
Efavirenz (EFV)
Alternative Regimen 1
(If preferred regimen is contraindicated or not available)
Zidovudine (AZT)
PLUS
Lamivudine (3TC)
PLUS
Efavirenz (EFV)
OR
Nevirapine (NVP)
Alternative Regimen 2
(If preferred regimen is contraindicated or not available)
Tenofovir (TDF)
PLUS
Emtricitabine (FTC)
OR
Lamivudine (3TC)
PLUS
Nevirapine (NVP)
Adapted from WHO 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection [4]
Second-line Regimen
If TDF + 3TC based regimen failed
Zidovudine (ZDV)
PLUS
Lamivudine (3TC)
PLUS
Ritonavir-boosted Atazanavir (ATV/r)
OR
Ritonavir-boosted Lopinavir (LPV/r)
If ZDV + 3TC based regimen failed
Tenofovir (TDF)
PLUS
Lamivudine (3TC)
PLUS
Ritonavir-boosted Atazanavir (ATV/r)
OR
Ritonavir-boosted Lopinavir (LPV/r)

National Institute of Health (NIH) Recommendations

▸ Click on the following categories to expand treatment regimens.

Recommended Regimens

  ▸  NNRTI-Based Regimen

  ▸  PI-Based Regimen

  ▸  INSTI-Based Regimen

Alternative Regimens

  ▸  PI-Based Regimen

  ▸  INSTI-Based Regimen

Recommended Regimen
NNRTI-Based Regimen
Efavirenz/Tenofovir/Emtricitabine
NNRTI-based regimen for patients with < 100,000 copies/mL
Efavirenz
PLUS
Abacavir/Lamivudine (only for HLA-B*5701 negative patients)
OR
Rilpivirine/Tenofovir/Emtricitabine (only for patients with CD4 < 200 cells/mm³)
Emtricitabine may be substituted for lamivudine or vice versa
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [5]
Recommended Regimen
PI-Based Regimen
Atazanavir/Ritonavir(low dose)
PLUS
Tenofovir/Emtricitabine
OR
Darunavir/Ritonavir(low dose)
PLUS
Tenofovir/Emtricitabine
PI-based regimen for patients with < 100,000 copies/mL
OR
Atazanavir/Ritonavir(low dose)
PLUS
Abacavir/Lamivudine (only for HLA-B*5701 negative patients)
Emtricitabine may be substituted for lamivudine or vice versa
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [5]
Recommended Regimen
INSTI-Based Regimen
Dolutegravir
PLUS
Abacavir/Lamivudine (only for HLA-B*5701 negative patients)
OR
Dolutegravir
PLUS
Tenofovir/Emtricitabine
OR
Elvitegravir/Cobicistat/Tenofovir/Emtricitabine(contraindicated in patients with CrCl <70mL/min)
OR
Raltegravir
PLUS
Tenofovir/Emtricitabine
Emtricitabine may be substituted for lamivudine or vice versa
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.[5]
Alternative Regimen
PI-Based Regimens
Darunavir/Ritonavir(low dose)
PLUS
Abacavir/Lamivudine (only for HLA-B*5701 negative patients)
OR
Lopinavir/Ritonavir(low dose)
PLUS
Abacavir/Lamivudine (only for HLA-B*5701 negative patients)
OR
Lopinavir/Ritonavir(low dose)
PLUS
Tenofovir/Emtricitabine
Emtricitabine may be substituted for lamivudine or vice versa
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [5]
Alternative Regimen
INSTI-Based Regimens
Raltegravir
PLUS
Abacavir/Lamivudine (only for HLA-B*5701 negative patients)
Emtricitabine may be substituted for lamivudine or vice versa
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [5]

Anti Retroviral Drug Classes

Drug Name Dose Adverse Events
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
300 mg BID or 600 mg once daily Fever, rash, nausea, vomiting, diarrhea, abdominal pain, malaise, fatigue, sore throat, cough, shortness of breath.
400 mg once daily
In combination with TDF: 200 mg once daily
Pancreatitis, nausea, vomiting, peripheral neuropathy, retinal changes, optic neuritis, lactic acidosis with hepatic steatosis.
200 mg once daily Hyperpigmentation, skin discoloration
250-300 mg BID Macrocytic anemia, neutropenia, nausea, vomiting, headache, insomnia, asthenia, nail pigmentation, lactic acidosis, severe hepatomegaly with hepatic steatosis (rare), hyperlipidemia, insulin resistance/diabetes mellitus, lipoatrophy, myopathy.
150 mg BID or 300 mg once daily Minimal toxicity, severe acute exacerbation of hepatitis may occur in HBV coinfected patients who discontinue 3TC.
>60 kg: 40 mg BID
<60 kg: 250 mg BID
Peripheral neuropathy, lipoatrophy, pancreatitis, lactic acidosis, severe hepatomegaly with hepatic steatosis (rare), hyperlipidemia, insulin resistance/diabetes mellitus, rapidly progressive ascending neuromuscular weakness (rare).
300 mg once daily Renal insufficiency, Fanconi syndrome, osteomalacia, decrease in bone mineral density, severe acute exacerbation of hepatitis may occur in HBV coinfected patients who discontinue TDF, asthenia, headache, diarrhea, nausea, vomiting, and flatulence.
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
600 mg once daily Rash, increased transaminase levels, hyperlipidemia, dizziness, somnolence, insomnia, depression, suicidality, confusion, abnormal thinking, impaired concentration, amnesia, agitation, depersonalization, hallucinations, and euphoria
200 mg BID Rash, Stevens-Johnson syndrome, nausea
200 mg once daily for 14 days, then 200 mg BID or 400 mg once daily Rash, Stevens-Johnson syndrome, nausea, hepatitis
25 mg once daily Rash, depression, insomnia, headache, hepatotoxicity
Protease Inhibitors (PIs)
400 mg once daily
In combination with TDF: 300 mg + RTV 100 mg once daily
In combination with EFV: 400 mg + RTV 100 mg once daily
Indirect hyperbilirubinemia, PR interval prolongation, hyperglycemia, fat maldistribution, cholelithiasis, nephrolithiasis, renal insufficiency, increase in transaminase levels, hyperlipidemia, skin rash
800 mg once daily Skin rash, Stevens-Johnson syndrome, hepatotoxicity, diarrhea, nausea, headache, hyperlipidemia, fat maldistribution, hyperglycemia.
1400 mg BID or
700 mg + RTV 100 mg BID
In combination with EFV: 700 mg + RTV 100 mg BID or 1400 mg + RTV 300 mg once daily
Skin rash, diarrhea, nausea, vomiting, headache, hyperlipidemia, hyperglycemia, increase in transaminase levels, nephrolithiasis, fat maldistribution.
800 mg q8h Nephrolithiasis, nausea, hepatitis, indirect hyperbilirubinemia, hyperlipidemia, headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, hemolytic anemia, hyperglycemia, fat maldistribution.
400 mg/100 mg BID or 800 mg/200 mg once daily Diarrhea, nausea, vomiting, pancreatitis, asthenia, hyperlipidemia, hyperglycemia, fat maldistribution, increase in transaminase levels, PR interval prolongation, insulin resistance/diabetes mellitus.
1250 md BID or 750 mg TID Diarrhea, hyperlipidemia, hyperglycemia, fat maldistribution, increase in transaminase levels.
100-400 mg/d q12-24h Diarrhea, nausea, vomiting, paresthesia, hyperlipidemia, hepatitis, asthenia, taste perversion, hyperglycemia, fat maldistribution.
1000 mg BID Diarrhea, nausea, vomiting, headache, hyperlipidemia, hyperglycemia, fat maldistribution, PR interval prolongation, insulin resistance/diabetes mellitus.
500 mg BID Hepatotoxicity, skin rash, hyperlipidemia, hyperglycemia, fat maldistribution.
Integrase Inhibitors
50 mg q12-24h Rash, insomnia, headache.
150 mg once daily Nausea, diarrhea, decrease bone density, severe acute exacerbation of hepatitis may occur in HBV coinfected patients.
400 mg BID Rash, Steven-Johnson syndrome, toxic epidermal necrolysis, nausea, headache, diarrhea, pyrexia, CPK elevation.
Fusion Inhibitor
90 mg SQ BID Local injection reactions, increased incidence of bacterial pneumonia, rash, fever, nausea.
CCR5 Antagonist
150-600 mg BID Abdominal pain, cough, dizziness, musculoskeletal symptoms, pyrexia, rash, upper respiratory tract infections, hepatotoxicity.
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [5]
CDC Grading of Recommendations and Levels of Evidence
Strength of recommendation Level of evidence
A. Strong I. One or more randomized trials with clinical outcomes and/or validated laboratory endpoint
B. Moderate II. One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes
C. Optional III. Expert opinion based on evaluation of other evidence

Recommendations for Initiating Antiretroviral Therapy

  • Antiretroviral therapy (ART) is recommended for all HIV-infected individuals. The strength of this recommendation varies on the basis of pretreatment CD4 cell count:
    • CD4 count <350 cells/mm3 (AI)
    • CD4 count 350 to 500 cells/mm3 (AII)
    • CD4 count >500 cells/mm3 (BIII)
  • Regardless of CD4 count, initiation of ART is strongly recommended for individuals with the following conditions:
  • Effective ART also has been shown to prevent transmission of HIV from an infected individual to a sexual partner; therefore, ART should be offered to patients who are at risk of transmitting HIV to sexual partners (AI [heterosexuals] or AIII [other transmission risk groups].
  • Patients starting ART should be willing and able to commit to treatment and should understand the benefits and risks of therapy and the importance of adherence (AIII). Patients may choose to postpone therapy, and providers, on a case by case basis, may elect to defer therapy on the basis of clinical and/or psychosocial factors.

Current Recommended Initial Oral ART for Most Persons with HIV Infection[6]

Bictegravir– FTC–TAF (50 mg/200 mg/25 mg),once daily as single-tablet regimen
Dolutegravir (50 mg),once daily
Plus TAF–FTC (25 mg/200 mg), once daily as single-tablet regimen
Plus TDF–FTC (300 mg/200 mg), once daily as single-tablet regimen
Plus TDF–3TC (300 mg/300 mg), Individual tablets each once daily
Dolutegravir–3TC (50 mg/300 mg), once daily as single-tablet regimen
  • Adverse effects: Gastrointestinal symptoms (nausea, diarrhea), IRIS, lactic acidosis, hepatic steatosis.
  • Do not use with lamivudine resistance (M184V or M184I mutation) or HBV infection; not recommended in patients with creatinine clearance <30 ml/min or Child–Pugh class B or C liver function; contraindicated with dofetilide; avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifapentine; use with caution with metformin.
  • Dolutegravir–3TC is not recommended for patients with rapid start of ART or for patients with chronic HBV infection, HIV RNA greater than 500,000 copies per milliliter, or a CD4 cell count of less than 200 cells/mm3.
Raltegravir (600 mg), two tablets once daily
Plus TAF–FTC (25 mg/200 mg), once daily as single-tablet regimen
Plus TDF–FTC (300 mg/200 mg), once daily as single-tablet regimen
Plus TDF–3TC (300 mg/300 mg), Individual tablets each once daily


Abbreviations

FTC emtricitabine

TAF tenofovir alafenamide fumarate,

TDF tenofovir disoproxil fumarate,

3TC lamivudine.



Treatment Failure

Definitions of Treatment Failure
Clinical Failure
  • New or recurrent WHO stage 4 condition
CD4 Cell Failure
  • Fall of CD4 count to pre-therapy baseline (or below), OR
  • 50% fall from the on-treatment peak value (if known), OR
  • Persistent CD4 levels below 100 cells/mm3
Virological Failure
  • Plasma viral load > 1 000 copies/ml
Table adapted from WHO Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection[4]
Treatment Failure Criteria Stage 1 Stage 2 Stage 3 Stage 4
CD4 cell failure Not recommended to switch regimen. Repeat CD4 count in 3 months Not recommended to switch regimen. Repeat CD4 count in 3 months Consider switching to second-line regimen Recommend to switch to second-line regimen
CD4 cell failure and viral load failure Consider second-line regimen Consider second-line regimen Recommended to switch to second-line regimen Recommended to switch to second-line regimen
Switching should not be done until the first regimen has been given sufficient time to succeed (at least 6 months).
Table adapted from WHO GUIDELINES ON ANTIRETROVIRAL THERAPY FOR HIV INFECTION IN ADULTS AND ADOLESCENTS [7]

Special Considerations

  • HAART allows the stabilization of the patient’s symptoms and viremia, but it neither cures the patient of HIV, nor alleviates the symptoms, and high levels of HIV-1, often HAART resistant, return once treatment is stopped.[8][9]
  • It would take more than the lifetime of an individual to be cleared of HIV infection using HAART.[10]
  • Many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality.[11][12][13]

HIV in Children

Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations are more aggressive for children than for adults.[14]

Treatment Adherence

Adherence is taking the correct dose of each anti-HIV medication at the correct time and exactly as prescribed. Adherence is very important for successful HIV treatment. The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, psychiatric disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues, along with side effects that create intentional non-adherence, also has a weighty impact.[15][16][17]

Difficulty in Adherence

There are several reasons why adhering to an HIV treatment regimen can be diicult. Most treatment regimens involve taking several pills every day with or without food, or before or after other medications. Other factors that can make treatment adherence difficult include:

  • Difficulty taking medications (such as trouble swallowing pills).
  • Side effects from medications (for example, fatigue or diarrhea).
  • Daily schedule issues (including a busy schedule, shift work, or travel away from home) .
  • Being sick or depressed .
  • Alcohol or drug abuse.

Importance of Adherence

Adherence effects the success of HIV treatment in two ways:

  • Good adherence to an HIV treatment regimen helps anti-HIV medications work effectively to reduce the viral load. Skipping medications, even occasionally, gives HIV to multiply rapidly. Preventing the virus from multiplying is the best way to stay healthy.
  • Good adherence to an HIV treatment regimen also helps prevent drug resistance. One or more anti-HIV medications in a treatment regimen can become ineffective as a result of drug resistance.

Skipping medications makes it easier for drug resistance to develop. HIV can develop resistance to the anti-HIV medications in a person’s current regimen or to other, similar anti-HIV medications not yet taken, limiting options for successful HIV treatment. And drug-resistant strains of HIV can be transmitted to others, too. Although there are many different anti-HIV medications and treatment regimens, studies show that a person’s first regimen offers the best chance for long-term treatment success. Adhering to the regimen from the start will help ensure that the HIV treatment is successful.

Virologic Response

The most reliable indicator of response to ART is plasma HIV RNA and should be measured in all patients at baseline and regularly during therapy.[18][19] It is thus useful in predicting clinical progression.

Viral load reduction may be more rapid in following patients:[20]

  • Having high CD4 cell count.
  • Having lower levels of baseline viremia.
  • In treatment-naive patients.
Time Expected decrease in Viral load
1 week Decrease by 0.75 to 1 log10 copies/mL
1 month Decrease by 1.5 to 2 log10 copies/mL to <5000 copies/mL .
2 to 4 months. <500 copies/mL
4 to 6 months. < 50 copies/mL.

Transient increase in the viral load can be present in acute illness and vaccinations.

Virologic Failure

It is defined either as primary failure to achieve a viral load <50 copies/mL or any sustained recurrence of viremia to >50 copies/mL after initial viral suppression.[21]

Two main causes of the failure are:

  1. Drug resistance.
  2. Failure of the drugs to reach the target site.

Viral Blips

It refer to an isolated low-level of detectable HIV RNA (>50 to 500 copies/mL) that occurs during long-term monitoring on a stable ART regimen.[22]

Department of Health and Human Services (DHHS) have suggested that viral blips do not require intervention with a new regimen unless the viral load is sustained at >200 copies/mL.

Monitoring CD4 and Viral Load

Scenario CD4 Monitoring Viral Load Monitoring
Before receiving ART Yes Yes
While receiving ART 3 month after initiation of ART 2-4 weeks after initiation of ART, then every 4-8 weeks
ART regimen is modified due to drug toxicity Will depend on previous CD4 counts 4-8 weeks after modification of regimen
ART regimen is modified due to virologic failure Every 3-6 months 2-4 weeks after initiation of ART, then every 4-8 weeks
During the first 2 years of ART Every 3-6 months Every 3-4 months
While on ART with detectable viremia (>200 copies/mL) Every 3-6 months Every 3 months
Change in clinical status
(new HIV clinical symptom or initiation of interferon, chronic systemic corticosteroids, or antineoplastic therapy)
Will depend on the clinical scenario Every 3 months
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [5]

Other Laboratory Monitoring

Time-point Laboratory Tests
At HIV diagnosis
At initiation of ART
After 2-8 weeks after ART initiation
Every 3-6 months
Every 6-12 months
  • Lipid profile
  • Urinalysis (if taking TDF)
  • HbA1c or fasting glucose (if abnormal previously)
Adapted from Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. [5]

Treatment Regimen

  • 1. Antiretroviral regimen options for treatment-naive patients[23][24]
  • 1.1. Integrase strand transfer inhibitor-based regimens
  • 1.2. Protease inhibitor-based regimen
  • 1.3. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen
  • 1.4. Other regimen options
  • 1.4.1. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen
  • Preferred regimen (1): Efavirenz 600 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative and with pre-treatment HIV RNA <100,000 copies/mL.
  • 1.4.2. Other regimens when tenofovir or abacavir cannot be used
  • 1.5. Pediatric doses
  • 20 to < 25 kg: 200 mg PO qd
  • 25 to < 60 kg: 250 mg PO qd
  • ≥60 kg: 400 mg PO qd
  • 10 to < 15 kg: 200 mg PO qd
  • 15 to <20 kg: 250 mg PO qd
  • 20 to < 25 kg: 300 mg PO qd
  • 25 to < 32.5 kg: 350 mg PO qd
  • 32.5 to <40 kg: 400 mg PO qd
  • ≥ 40 kg: 600 mg PO qd
  • Between 1 day and 8 years: 200 mg/m2/dose PO qd for 14 days, then 200 mg/m2/dose PO bid
  • 8 years and above: 120-150 mg/m2/dose PO qd for 14 days, then 120-150 mg/m2/dose PO bid
  • Note (1): Anti retroviral therapy for treatment naive patients is a life long therapy.
  • Note (2): Tenofovir disoproxil fumarate should be avoided in patients with a creatinine clearance <50 mL/min.
  • Note (3): Rilpivirine should be used in patients with a CD4 cell count >200 copies/mL and should not be used with proton pump inhibitors.
  • Note (4): Efavirenz should not be used in pregnant women.
  • 2. Pre-exposure prophylaxis (PrEP)
  • Preferred regimen: Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd for ≤90-days
  • Note (1): People with high risk behavior such as men who have sex with men, intravenous drug abusers, HIV-positive sexual partner, recent bacterial STI, high number of sex partners, history of inconsistent or no condom use, commercial sex work, people in high-prevalence area or network are advised to take pre-exposure prophylaxis of drugs.
  • Note (2): Follow-up visits at least every 3 months to provide the following: HIV test, medication adherence counseling, behavioral risk reduction support, side effect assessment, STI symptom assessment, pregnancy testing.
  • Note (3): At 3 months and every 6 months thereafter, assess renal function.
  • Note (4): Every 6 months, test for bacterial STIs.
  • 3. Post- exposure prophylaxis
  • 4. Perinatal antiretroviral regimen
  • 4.1. Antepartum
  • 4.1.1. Protease inhibitor-based regimen
  • 4.1.2. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen:
  • 4.2. Intrapartum
  • Note (1): HIV RNA <1000 copies/mL and good adherance-Continue the regimen during delivery or cessarean section.
  • Note (2): HIV RNA >1000 copies/mL near delivery, possible poor adherence, or unknown HIV RNA levels- Intravenous Zidovudine 2 mg/kg IV over 1 hr should be given three hours before cesarean section or delivery and then 1 mg/kg/hr IV continuous infusion until umbilical cord clamping.
  • 4.3. Postpartum
  • Note: Initiate anti retroviral therapy (ART) and continue after delivery and cessation of breastfeeding.
  • 5. Infant antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV
  • 5.1 Prophylaxis for HIV-exposed infants of women who received antepartum antiretroviral prophylaxis
  • Preferred regimen: Zidovudine (ZDV) 100 mg PO given at birth and continued till six weeks
  • Note (1): Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
  • Note (2): ≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
  • Note (3): ≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
  • Note (4): <30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.
  • 5.2. Prophylaxis for HIV-exposed infants of women who received no antepartum antiretroviral prophylaxis
Nevirapine
  • Dose based on birth weight, initiated as soon after birth as possible.
  • Birth weight 1.5 to 2 kg: 8 mg/dose orally.
  • Birth weight >2 kg: 12 mg/dose orally.
AND
Zidovudine (ZDV)
  • Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
  • ≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
  • ≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
  • <30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.
  • Note (1): Three doses in the first week of life.
  • Note (2): First dose within 48 hours of birth (birth to 48 hrs).
  • Note (3): Second dose 48 hours after first.
  • Note (4): Third dose 96 hours after second.

Primary Prophylaxis against Opportunistic Infections in Persons with HIV Infection[25]

Prophylaxis against Pneumocystis jirovecii

  • Indications: CD4 count <200 cells/mm3 or thrush
  • Drugs used:
    • Trimethoprim–sulfamethoxazole one double-strength tablet (160 mg of trimethoprim and 800 mg of sulfamethoxazole) daily or 3 times/week
    • Dapsone 100 mg, orally once daily
    • Pentamidine 300 mg, aerosolized through nebulizer monthly
    • Atovaquone 1500 mg, orally (liquid suspension) daily

Prophylaxis against cryptococcus

  • Indications: CD4 count <100 cells/mm3 and positive serum cryptococcal antigen
  • Drug used: fluconazole 200 mg, orally once daily

Prophylaxis against histoplasmosis

  • Indications: CD4 count <150 cells/mm3 in areas where histoplasmosis is endemic

Prophylaxis against Mycobacterium avium complex

It is no longer recommended in patient with rapid initiation of ART

Management of HIV-patients

The 2021 CDC STD guidelines recommend the following steps to be taken with every patient diagnosed with HIV:[26]

  • Link persons with HIV infection to care and start them on ART as soon as possible.
  • Report cases (in accordance with local requirements) to public health and initiate partner services.
  • Provide prevention counseling to persons with diagnosed HIV infection.
  • Ensure all persons with HIV infection are informed that if they achieve and maintain a suppressed viral load, they have effectively no risk for transmitting HIV. Stress that a suppressed viral load is not a substitute for condoms and behavioral modifications because ART does not protect persons with HIV against other STIs.
  • Provide additional counseling, either on-site or through referral, about the psychosocial and medical implications of having HIV infection.
  • Assess the need for immediate medical care and psychosocial support.
  • Link persons with diagnosed HIV infection to services provided by health care personnel experienced in managing HIV infection. Additional services that might be needed include substance misuse counseling and treatment, treatment for mental health disorders or emotional distress, reproductive counseling, risk-reduction counseling, and case management. Providers should follow up to ensure that patients have received services for any identified needs.
  • Persons with HIV infection should be educated about the importance of ongoing medical care and what to expect from these services.

References

  1. Sterne JA, Hernán MA, Ledergerber B, Tilling K, Weber R, Sendi P, Rickenbach M, Robins JM, Egger M (2005). "Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study". Lancet. 366 (9483): 378–84. doi:10.1016/S0140-6736(05)67022-5. PMID 16054937. Retrieved 2012-02-15.
  2. Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Johnson VA, Morse GD, Nokta MA, Martinez AI, Gripshover BM, Kaul P, Haubrich R, Swingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC (2003). "Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection". N. Engl. J. Med. 349 (24): 2304–15. doi:10.1056/NEJMoa030265. PMID 14668456. Retrieved 2012-02-16. Unknown parameter |month= ignored (help)
  3. Puls RL, Srasuebkul P, Petoumenos K, Boesecke C, Duncombe C, Belloso WH, Molina JM, Li L, Avihingsanon A, Gazzard B, Cooper DA, Emery S (2010). "Efavirenz versus boosted atazanavir or zidovudine and abacavir in antiretroviral treatment-naive, HIV-infected subjects: week 48 data from the Altair study". Clin. Infect. Dis. 51 (7): 855–64. doi:10.1086/656363. PMID 20735258. Retrieved 2012-02-16. Unknown parameter |month= ignored (help)
  4. 4.0 4.1 "WHO 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection" (PDF).
  5. 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014".
  6. Saag MS (2021). "HIV Infection - Screening, Diagnosis, and Treatment". N Engl J Med. 384 (22): 2131–2143. doi:10.1056/NEJMcp1915826. PMID 34077645 Check |pmid= value (help).
  7. "WHO GUIDELINES ON ANTIRETROVIRAL THERAPY FOR HIV INFECTION IN ADULTS AND ADOLESCENTS" (PDF).
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  9. Dybul M, Fauci AS, Bartlett JG, Kaplan JE, Pau AK; Panel on Clinical Practices for Treatment of HIV. (2002). "Guidelines for using antiretroviral agents among HIV-infected adults and adolescents". Ann. Intern. Med. 137 (5 Pt 2): 381&ndash, 433. PMID 12617573.
  10. Blankson JN, Persaud D, Siliciano RF (2002). "The challenge of viral reservoirs in HIV-1 infection". Annu. Rev. Med. 53: 557&ndash, 593. PMID 11818490.
  11. Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998). "Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection". N. Engl. J. Med. 338 (13): 853&ndash, 860. PMID 9516219.
  12. Wood E, Hogg RS, Yip B, Harrigan PR, O'Shaughnessy MV, Montaner JS (2003). "Is there a baseline CD4 cell count that precludes a survival response to modern antiretroviral therapy?". AIDS. 17 (5): 711&ndash, 720. PMID 12646794.
  13. Chene G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, Dabis F, Lundgren J, D'Arminio Monforte A, de Wolf F, Hogg R, Reiss P, Justice A, Leport C, Staszewski S, Gill J, Fatkenheuer G, Egger ME and the Antiretroviral Therapy Cohort Collaboration (2003). "Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies". Lancet. 362 (9385): 679&ndash, 686. doi:10.1016/S0140-6736(03)14229-8. PMID 12957089.
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