HIV AIDS medical therapy: Difference between revisions

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<!---
====Recommendations for Initiating Antiretroviral Therapy====
===Initiation of ART===
*Antiretroviral therapy (ART) is recommended for all HIV-infected individuals. The strength of this recommendation varies on the basis of pretreatment CD4 cell count:
<center>
** CD4 count <350 cells/mm3 ('''AI''')
{| border="1"
** CD4 count 350 to 500 cells/mm3 ('''AII''')
|+
** CD4 count >500 cells/mm3 ('''BIII''')
|
| Year
| AIDS/Symptoms
| CD4 <200
| CD4 200-350
| CD4 350-500
| CD4 >500
|-
| DHHS [http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf]
| 2011
| Yes
| Yes
| Yes
| Yes
| Yes (optional)
|-
| IAS-USA<ref name="pmid20639566">{{cite journal |author=Thompson MA, Aberg JA, Cahn P, Montaner JS, Rizzardini G, Telenti A, Gatell JM, Günthard HF, Hammer SM, Hirsch MS, Jacobsen DM, Reiss P, Richman DD, Volberding PA, Yeni P, Schooley RT |title=Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel |journal=JAMA |volume=304 |issue=3 |pages=321–33 |year=2010 |month=July |pmid=20639566 |doi=10.1001/jama.2010.1004 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=20639566 |accessdate=2012-03-08}}</ref>
| 2010
| Yes
| Yes
| Yes
| Yes
| Consider
|-
| UK
| 2008
| Yes
| Yes
| Yes
| Clinical trial
| Clinical trial
|-
| EACS<ref name="pmid18257769">{{cite journal |author=Clumeck N, Pozniak A, Raffi F |title=European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of HIV-infected adults |journal=HIV Med. |volume=9 |issue=2 |pages=65–71 |year=2008 |month=February |pmid=18257769 |doi=10.1111/j.1468-1293.2007.00533.x |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1464-2662&date=2008&volume=9&issue=2&spage=65 |accessdate=2012-03-08}}</ref>
| 2011
| Yes
| Yes
| Yes
| Consider
| Defer
|-
| WHO [[http://www.who.int/hiv/pub/guidelines/artadultguidelines.pdf]]
| 2010
| Yes
| Yes
| Yes
| No
| No
|}
</center>


===Indications===
*Regardless of CD4 count, initiation of ART is strongly recommended for individuals with the following conditions:
The DHHS guidelines currently recommend the follwing:
** Pregnancy ('''AI''')
 
** History of an AIDS-defining illness ('''AI''')
{|border="1" align="center" style="background:white"
** [[HIV associated nephropathy]] (HIVAN) ('''AII''')
|-
** HIV/[[hepatitis B virus]] (HBV) coinfection ('''AII''')
| bgcolor="white" |'''Symptoms'''
*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].
| bgcolor="white" |'''CD4 count'''
* 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.
| bgcolor="white" |'''Treatment'''
|-
| Asymptomatic
| <500
| Treatment should be offered.
|-
| Asymptomatic
| >500
| Treatment is optional.
|-
| [[AIDS history and symptoms#History and Symptoms|Symptomatic]]
| Any value
| Treatment should be initiated.<ref name="pmid20639566">{{cite journal |author=Thompson MA, Aberg JA, Cahn P, Montaner JS, Rizzardini G, Telenti A, Gatell JM, Günthard HF, Hammer SM, Hirsch MS, Jacobsen DM, Reiss P, Richman DD, Volberding PA, Yeni P, Schooley RT |title=Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel |journal=JAMA |volume=304 |issue=3 |pages=321–33 |year=2010 |month=July |pmid=20639566 |doi=10.1001/jama.2010.1004 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=20639566 |accessdate=2012-02-15}}</ref>
|}
 
 
 
====B. International AIDS Society-USA (IAS-USA) Guidelines ====
In agreement with the DHHS guidelines mentioned above, IAS-USA recommend the following:<ref name="pmid20639566">{{cite journal |author=Thompson MA, Aberg JA, Cahn P, Montaner JS, Rizzardini G, Telenti A, Gatell JM, Günthard HF, Hammer SM, Hirsch MS, Jacobsen DM, Reiss P, Richman DD, Volberding PA, Yeni P, Schooley RT |title=Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel |journal=JAMA |volume=304 |issue=3 |pages=321–33 |year=2010 |month=July |pmid=20639566 |doi=10.1001/jama.2010.1004 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=20639566 |accessdate=2012-02-21}}</ref>
*Fixed-dose TDF/FTC as the preferred NRTI for combination ART.
*If [[HLA-B|HLA B5701]] testing is negative, then [[abacavir]]/[[lamivudine]] is used as an alternative choice.
 
 
 
===Initial HIV Therapy===
 
NNRTI, PI, or [[integrase]] inhibitor-based regimen in combination with dual NRTIs is considered as an initial HIV therapy. Currently, [[CCR5]] inhibitors are not recommended due to lack of sufficient published data.  The particular choice of agent depends on the following factors:
*Side effect profiles.
*Comorbidities in patient.
*Potential drug interactions.
*[[Allergy]] history.
*[[Pregnancy]] status.
*Patient convenience.
 
=== Highly Active Anti-Retroviral Therapy ===
*Current treatment for HIV infection consists of [[highly active antiretroviral therapy]], or HAART.<ref name=DhhsHivTreatment>{{
 
  cite web
| publisher=Department of Health and Human Services
| date=February 2006
| url=http://hab.hrsa.gov/tools/HIVpocketguide/PktGARTtables.htm
| title=A Pocket Guide to Adult HIV/AIDS Treatment February 2006 edition
| accessdate = 2006-09-01
 
}}</ref> This has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available. [[Image:Abacavir (Ziagen) 300mg.jpg|left|thumb|100px|''[[Abacavir]]'' – a nucleoside analog reverse transcriptase inhibitors (NARTIs or NRTIs)]]
 
*In developed countries where HAART is available, doctors assess the [[viral load]], rapidity in CD4 decline, and patient readiness while deciding when to recommend initiating treatment.<ref name=2005DhhsHivTreatment>{{
 
cite web
| publisher=Department of Health and Human Services Panel on Clinical Practices for Treatment of HIV Infection
| date=2005-10-06
| url=http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
| title=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents
| format= PDF
| accessdate = 2006-01-17
 
}}</ref>
 
*In the absence of HAART, progression from HIV infection to AIDS occurs at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2&nbsp;months.
 
*HAART is thought to increase survival time by between 4 and 12&nbsp;years.<ref name=JTKing>{{
 
cite journal
| author=King JT, Justice AC, Roberts MS, Chang CH, Fusco JS and the CHORUS Program Team
| title=Long-Term HIV/AIDS Survival Estimation in the Highly Active Antiretroviral Therapy Era
| journal=Medical Decision Making | year=2003 | pages=9&ndash;20 | volume=23 | issue=1
| pmid=12583451
 
}}</ref><ref name=Tassie>{{
 
cite journal
| author=Tassie JM, Grabar S, Lancar R, Deloumeaux J, Bentata M, Costagliola D and the Clinical Epidemiology Group from the French Hospital Database on HIV
| title=Time to AIDS from 1992 to 1999 in HIV-1-infected subjects with known date of infection
| journal=Journal of acquired immune deficiency syndromes | year=2002 | pages=81&ndash;7 | volume=30 | issue=1
| pmid=12048367
 
}}</ref> This average reflects the fact that for some patients &ndash; and in many clinical cohorts this may be more than fifty percent of patients &ndash; HAART achieves far less than optimal results. This is due to a variety of reasons such as medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV.
*Non-adherence and non-persistence with antiretroviral therapy is the major reason most individuals fail to get any benefit from and develop resistance to HAART.<ref name=becker>{{
 
cite journal
| author=Becker SL, Dezii CM, Burtcel B, Kawabata H, Hodder S. | title=Young HIV-infected adults are at greater risk for medication nonadherence | journal=MedGenMed. | year=2002 | pages=21 | volume=4| issue=3 | pmid=12466764
 
}}</ref>
*The side effects include [[lipodystrophy]], [[dyslipidaemia]], [[insulin resistance]], an increase in [[cardiovascular]] risks and [[birth defect]]s.<ref name=Montessori>{{
 
cite journal |
author=Montessori V, Press N, Harris M, Akagi L, Montaner JS |
title=Adverse effects of antiretroviral therapy for HIV infection. |
journal=CMAJ | year=2004 | pages=229&ndash;238 | volume=170 | issue=2 | pmid=14734438
 
}}</ref><ref name=Saitoh>{{
 
cite journal
| author=Saitoh A, Hull AD, Franklin P, Spector SA
| title=Myelomeningocele in an infant with intrauterine exposure to efavirenz
| journal=J. Perinatol. | year=2005 | pages=555&ndash;556 | volume=25 | issue=8
| pmid=16047034 | doi=10.1038/sj.jp.7211343
 
}}</ref>
* '''Side-Effect of HAART:''' Treatment optimism after the initial successes of HAART likely affected the subsequent dynamics of HIV because these favorable treatment outcomes led some persons to increase their high-risk behavior.


===Special Considerations===
===Special Considerations===
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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.
===Visit Frequency===
Patients who are started on ART should generally have follow-up within one to two weeks. Patient should be asked about the following:
* [[Antiretroviral drug#Adverse effects|Adverse effects]].
* [[AIDS medical therapy#Treatment Adherence|Adherence]].
* [[AIDS primary prevention#Prevention of sexual transmission of HIV|Prevention of transmission]].
Visit frequency of patients who are clinically stable on their ART regimen, can be decrease to every three months.
===General Laboratory Investigations===
The following lab tests are advised at baseline and at scheduled follow-up:
* [[Complete blood count]] with differential
* [[BUN]] and [[creatinine]]
* [[Liver function tests]]
More frequent testing is indicated in the following conditions:
* If mild or moderate abnormalities are detected and the medication is continued.
* Depending on the drug prescribed
** In patients on [[nevirapine]], some experts recommend monitoring at 0, 2, 4, 8, 12 weeks and then every 3 months.
** Women in childbearing age-group, should have a pregnancy test, before initiation of potential [[teratogen]]ic drugs like [[efavirenz]].
** In patients taking [[zidovudine]], [[hematologic]] monitoring is important as the drug causes [[bone marrow suppression]].
**In patients taking [[tenofovir]], which can cause [[renal insufficiency]], monitoring of [[creatinine]] and [[urinalysis]] every six months is necessary.<ref name="pmid18171278">{{cite journal |author=Szczech LA |title=Tenofovir nephrotoxicity: focusing research questions and putting them into clinical context |journal=J. Infect. Dis. |volume=197 |issue=1 |pages=7–9 |year=2008 |month=January |pmid=18171278 |doi=10.1086/524091 |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=18171278 |accessdate=2012-02-18}}</ref>


===Virologic Response===
===Virologic Response===
Line 637: Line 466:
* In treatment-naive patients.
* In treatment-naive patients.


{|border="1" align="center" style="background:white"
{| style="border: 0px; font-size: 90%; margin: 3px; width: 500px; float:center" align=center
|-
|valign=top|
| bgcolor="white" |''' Time '''
|+
| bgcolor="white" |'''Expected decrease in Viral load'''
! style="background: #4479BA; color:#FFF;  width: 200px;" |''' Time '''
! style="background: #4479BA; color:#FFF;  width: 200px;" |'''Expected decrease in Viral load'''
|-
|-
| 1 week
| style="padding: 5px 5px; background: #DCDCDC"| 1 week
| decrease by 0.75 to 1 log10 copies/mL
| style="padding: 5px 5px; background: #F5F5F5;" | Decrease by 0.75 to 1 log10 copies/mL
|-
|-
| 1 month  
| style="padding: 5px 5px; background: #DCDCDC"| 1 month  
| 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 .
|-
|-
| 2 to 4 months.  
| style="padding: 5px 5px; background: #DCDCDC"| 2 to 4 months.  
| <500 copies/mL  
| style="padding: 5px 5px; background: #F5F5F5;" | <500 copies/mL  
|-
|-
| 4 to 6 months.
| style="padding: 5px 5px; background: #DCDCDC"|4 to 6 months.
| < 50 copies/mL.
| style="padding: 5px 5px; background: #F5F5F5;" | < 50 copies/mL.
 
|}
|}


Transient increase in the viral load can be present in acute illness and [[vaccination]]s.
Transient increase in the viral load can be present in acute illness and [[vaccination]]s.


===Virologic Failure===
===Virologic Failure===
Line 671: Line 499:
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.


==Indications for Modification of Therapy ==
<!---
Common indications for the change of therapy are as follows:
* [[AIDS medical therapy#Virologic failure|Virologic failure]] : It should be confirmed with a second test before any treatment modification is considered.
* Toxicity
* Intolerance
* Inconvenience
 
==Alternate Therapies==
 
Various forms of [[alternative medicine]] have been used to treat symptoms or alter the course of the disease.<ref name=Saltmarsh>{{
 
cite journal
| author=Saltmarsh S
| title=Voodoo or valid? Alternative therapies benefit those living with HIV
| journal=Positively Aware | year=2005 | pages=46 | volume=3 | issue=16
| pmid=16479668 | url=http://www.tpan.com/publications/pa/may_jun_05/voodoo.shtml
 
}}
</ref> In the first decade of the [[epidemic]] when no useful conventional treatment was available, a large number of people with AIDS experimented with alternative therapies. The definition of "alternative therapies" in AIDS has changed since that time. Then, the phrase often referred to community-driven treatments, untested by government or pharmaceutical company research, that some hoped would directly suppress the virus or stimulate immunity against it. Examples of alternative medicine that people hoped would improve their symptoms or their quality of life include massage, stress management, herbal and flower remedies such as boxwood,<ref name=Pharo>{{
 
cite journal
| author=Pharo A, et al
| title=Evaluation of the safety and efficacy of SPV-30 (boxwood extract) in patients with HIV disease
| journal=Int Conf AIDS | year=1996 | issue=Jul 7–12 | pages=11:19 | id=abstract no. Mo. B.180
| url=http://www.aegis.org/conferences/iac/1996/MoB180.html
 
}}
</ref><ref name=Durant>{{
 
cite journal
| author=Durant J, et al
| title=Efficacy and safety of Buxussempervirens L. preparations (SPV-30) in HIV infected asymptomatic patients: a multi-centre, randomized, double-blind, placebo-controlled trial.
| journal=Phytomedicine | year = 1998 | issue=5 | pages=1–10
 
}}
</ref> and [[acupuncture]];<ref name=Saltmarsh /> when used with conventional treatment, many now refer to these as "complementary" approaches. Despite the widespread use of complementary and alternative medicine by people living with HIV/AIDS, the effectiveness of these therapies has not been established.<ref name=Mills>{{
 
cite journal
| author=Mills E, Wu P, Ernst E
| title=Complementary therapies for the treatment of HIV: in search of the evidence.
| journal=Int. J. STD AIDS.| year=2005 | pages=395&ndash;403 | volume=16 | issue=6
| pmid=15969772
 
}}</ref>
 
==NIH Recommendations==
===NIH Recommendations:Treatment-Naive Patients===
====NIH Recommendations for Initiating Antiretroviral Therapy in Treatment-Naive Patients====
*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:
** Pregnancy ('''AI''')
** History of an AIDS-defining illness ('''AI''')
** [[HIV associated nephropathy]] (HIVAN) ('''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].
* 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.
 
====What to Start: Initial Combination Regimens for the Antiretroviral-Naive Patient====
The Panel recommends the following as preferred regimens for antiretroviral (ARV)-naive patients:
* [[efavirenz]]/[[tenofovir]]/[[emtricitabine]] (EFV/TDF/FTC) ('''AI''')
* [[ritonavir]]-boosted [[atazanavir]] + tenofovir/emtricitabine (ATV/r + TDF/FTC) ('''AI''')
* ritonavir-boosted [[darunavir]] + tenofovir/emtricitabine (DRV/r + TDF/FTC) ('''AI''')
* [[raltegravir]] + tenofovir/emtricitabine (RAL + TDF/FTC) ('''AI''').
* Selection of a regimen should be individualized on the basis of virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance testing results, and comorbid conditions.
* Based on individual patient characteristics and needs, in some instances, an alternative regimen may actually be a preferred regimen for a patient.
 
===NIH Recommendations:Treatment-Experienced Patient===
===NIH Recommendations:Treatment-Experienced Patient===
====NIH recommendations for Virologic and Immunologic Failure====
====NIH recommendations for Virologic and Immunologic Failure====
Line 783: Line 542:
* HIV experts and primary care providers should work together to optimize the medical care of older HIV-infected patients with complex comorbidities.
* HIV experts and primary care providers should work together to optimize the medical care of older HIV-infected patients with complex comorbidities.
* Counseling to prevent secondary transmission of HIV remains an important aspect of the care of the older HIV infected patient.
* Counseling to prevent secondary transmission of HIV remains an important aspect of the care of the older HIV infected patient.
--->
--->


Revision as of 19:06, 2 October 2014

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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]

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 assays. 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.

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]
  • Antiretroviral therapy should be initiated in the following patient populations:
  • Treatment failure is defined by the following factors:
  • Virologic failure: which is defined as suboptimal viral suppression or loss of suppression (>50 HIV-1 RNA copies/mL).
  • Immunologic failure : which is defined as failure to achieve or maintain CD4 cell count recovery despite effective viral suppression.
  • Development of new opportunistic infections or neoplasms despite apparent CD4 count recovery.

Anti Retroviral Regimens

▸ 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 HIV RNA < 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. [4]
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 HIV RNA < 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. [4]
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.[4]
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. [4]
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. [4]

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. [4]

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.

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.[5][6] Moreover, it would take more than the lifetime of an individual to be cleared of HIV infection using HAART.[7] 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.[8][9][10]

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.[11]

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.[12][13][14]

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.[15][16] It is thus useful in predicting clinical progression.

Viral load reduction may be more rapid in following patients:[17]

  • 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.[18]

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.[19]

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. [4]

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. [4]

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 4.2 4.3 4.4 4.5 4.6 4.7 "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, AIDS info 2014".
  5. ↑ Martinez-Picado J, DePasquale MP, Kartsonis N; et al. (2000). "Antiretroviral resistance during successful therapy of human immunodeficiency virus type 1 infection". Proc. Natl. Acad. Sci. U. S. A. 97 (20): 10948&ndash, 10953. PMID 11005867.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ "Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection" (PDF). Department of Health and Human Services Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. 2005-11-03. Retrieved 2006-01-17.
  12. ↑ 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 (2001). "Limited Patient Adherence to Highly Active Antiretroviral Therapy for HIV-1 Infection in an Observational Cohort Study". Arch. Intern. Med. 161 (16): 1962&ndash, 1968. PMID 11525698.
  13. ↑ Kleeberger C, Phair J, Strathdee S, Detels R, Kingsley L, Jacobson LP (2001). "Determinants of Heterogeneous Adherence to HIV-Antiretroviral Therapies in the Multicenter AIDS Cohort Study". J. Acquir. Immune Defic. Syndr. 26 (1): 82&ndash, 92. PMID 11176272.
  14. ↑ Heath KV, Singer J, O'Shaughnessy MV, Montaner JS, Hogg RS (2002). "Intentional Nonadherence Due to Adverse Symptoms Associated With Antiretroviral Therapy". J. Acquir. Immune Defic. Syndr. 31 (2): 211&ndash, 217. PMID 12394800.
  15. ↑ Thiébaut R, Morlat P, Jacqmin-Gadda H, Neau D, Mercié P, Dabis F, Chêne G (2000). "Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA)". AIDS. 14 (8): 971–8. PMID 10853978. Retrieved 2012-02-19. Unknown parameter |month= ignored (help)
  16. ↑ Hughes MD, Johnson VA, Hirsch MS, Bremer JW, Elbeik T, Erice A, Kuritzkes DR, Scott WA, Spector SA, Basgoz N, Fischl MA, D'Aquila RT (1997). "Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response. ACTG 241 Protocol Virology Substudy Team". Ann. Intern. Med. 126 (12): 929–38. PMID 9182469. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  17. ↑ 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 (2002). "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". J. Infect. Dis. 185 (7): 905–14. doi:10.1086/339295. PMID 11920314. Retrieved 2012-02-19. Unknown parameter |month= ignored (help)
  18. ↑ Thompson MA, Aberg JA, Cahn P, Montaner JS, Rizzardini G, Telenti A, Gatell JM, Günthard HF, Hammer SM, Hirsch MS, Jacobsen DM, Reiss P, Richman DD, Volberding PA, Yeni P, Schooley RT (2010). "Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA panel". JAMA. 304 (3): 321–33. doi:10.1001/jama.2010.1004. PMID 20639566. Retrieved 2012-02-20. Unknown parameter |month= ignored (help)
  19. ↑ Sungkanuparph S, Overton ET, Seyfried W, Groger RK, Fraser VJ, Powderly WG (2005). "Intermittent episodes of detectable HIV viremia in patients receiving nonnucleoside reverse-transcriptase inhibitor-based or protease inhibitor-based highly active antiretroviral therapy regimens are equivalent in incidence and prognosis". Clin. Infect. Dis. 41 (9): 1326–32. doi:10.1086/496985. PMID 16206110. Retrieved 2012-02-21. Unknown parameter |month= ignored (help)
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