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| {{ | | {{HIV opportunistic infections}} |
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| HIV opportunistic infections}} | |
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| {{CMG}} | | {{CMG}} |
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| ==Overview== | | ==[[HIV opportunistic infections overview|Overview]]== |
| Before the widespread use of potent combination antiretroviral therapy (ART), opportunistic infections (OIs), which have been defined as infections that are more frequent or more severe because of immunosuppression in HIV-infected persons, were the principal cause of morbidity and mortality in this population. In the early 1990s, the use of chemoprophylaxis, immunization, and better strategies for managing acute OIs contributed to improved quality of life and improved survival.<ref name="pmid16741877">{{cite journal |author=Walensky RP, Paltiel AD, Losina E, Mercincavage LM, Schackman BR, Sax PE, Weinstein MC, Freedberg KA |title=The survival benefits of AIDS treatment in the United States |journal=J. Infect. Dis. |volume=194 |issue=1 |pages=11–9 |year=2006 |month=July |pmid=16741877 |doi=10.1086/505147 |url=http://www.jid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16741877 |accessdate=2012-04-05}}</ref> However, the widespread use of ART starting in the mid-1990s has had the most profound influence on reducing OI-related mortality in HIV-infected persons in those countries in which these therapies are accessible and affordable.
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| ==Etiology== | | ==[[HIV opportunistic infections historical perspective|Historical Perspective]]== |
| Despite the availability of ART in the United States and other industrialized countries, OIs continue to cause considerable morbidity and mortality for three primary reasons:
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| *Many patients are unaware of their HIV infection and seek medical care when an OI becomes the initial indicator of their disease.
| | ==[[HIV opportunistic infections classification|Classification]]== |
| *Certain patients are aware of their HIV infection, but do not take ART because of psychosocial or economic factors.
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| *Certain patients are prescribed ART, but fail to attain adequate virologic and immunologic response because of factors related to adherence, pharmacokinetics, or unexplained biologic factors.<ref name="pmid16011527">{{cite journal |author=Perbost I, Malafronte B, Pradier C, Santo LD, Dunais B, Counillon E, Vinti H, Enel P, Fuzibet JG, Cassuto JP, Dellamonica P |title=In the era of highly active antiretroviral therapy, why are HIV-infected patients still admitted to hospital for an inaugural opportunistic infection? |journal=HIV Med. |volume=6 |issue=4 |pages=232–9 |year=2005 |month=July |pmid=16011527 |doi=10.1111/j.1468-1293.2005.00282.x |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1464-2662&date=2005&volume=6&issue=4&spage=232 |accessdate=2012-04-05}}</ref><ref name="pmid16494634">{{cite journal |author=Palacios R, Hidalgo A, Reina C, de la Torre M, Márquez M, Santos J |title=Effect of antiretroviral therapy on admissions of HIV-infected patients to an intensive care unit |journal=HIV Med. |volume=7 |issue=3 |pages=193–6 |year=2006 |month=April |pmid=16494634 |doi=10.1111/j.1468-1293.2006.00353.x |url=http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1464-2662&date=2006&volume=7&issue=3&spage=193 |accessdate=2012-04-05}}</ref>
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| Thus, although hospitalizations and deaths have decreased since the implementation of ART, OIs remain a leading cause of morbidity and mortality in HIV-infected persons.<ref name="pmid16116306">{{cite journal |author=Gebo KA, Fleishman JA, Reilly ED, Moore RD |title=High rates of primary Mycobacterium avium complex and Pneumocystis jiroveci prophylaxis in the United States |journal=Med Care |volume=43 |issue=9 Suppl |pages=III23–30 |year=2005 |month=September |pmid=16116306 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0025-7079&volume=43&issue=9&spage=III23 |accessdate=2012-04-05}}</ref><ref name="pmid16089023">{{cite journal |author=Bonnet F, Lewden C, May T, Heripret L, Jougla E, Bevilacqua S, Costagliola D, Salmon D, Chêne G, Morlat P |title=Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France |journal=Scand. J. Infect. Dis. |volume=37 |issue=6-7 |pages=482–7 |year=2005 |pmid=16089023 |doi= |url= |accessdate=2012-04-05}}</ref><ref name="pmid17304464">{{cite journal |author=Teshale EH, Hanson DL, Wolfe MI, Brooks JT, Kaplan JE, Bort Z, Sullivan PS |title=Reasons for lack of appropriate receipt of primary Pneumocystis jiroveci pneumonia prophylaxis among HIV-infected persons receiving treatment in the United States: 1994-2003 |journal=Clin. Infect. Dis. |volume=44 |issue=6 |pages=879–83 |year=2007 |month=March |pmid=17304464 |doi=10.1086/511862 |url=http://www.cid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=17304464 |accessdate=2012-04-05}}</ref>
| | ==[[HIV opportunistic infections pathophysiology|Pathophysiology]]== |
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| ==Pathophysiology== | | ==[[HIV opportunistic infections causes|Causes]]== |
| Recognizing that the relation between OIs and HIV infection is bidirectional is important. HIV leads to immunosuppression that allows opportunistic pathogens to cause disease in HIV-infected persons. OIs and other coinfections that might be common in HIV-infected persons, such as sexually transmitted infections, can also have adverse effects on the natural history of HIV infection. Certain OIs are associated with reversible increases in circulating viral load and these increases could lead to accelerated HIV progression or increased transmission of HIV. Thus, although chemoprophylaxis and vaccination directly prevent pathogen-specific morbidity and mortality, they might also contribute to reduced rate of progression of HIV disease. For instance, randomized trials using [[trimethoprim]]-[[sulfamethoxazole]] (TMP-SMX) have documented that [[chemoprophylaxis]] can both decrease OI-related [[morbidity]] and improve [[survival]].
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| ==Historical Perspective== | | ==[[HIV opportunistic infections differential diagnosis|Differentiating HIV opportunistic infections from other Diseases]]== |
| The first guidelines for Prophylaxis against Pneumocystis carinii Pneumonia for persons infected with the human immunodeficiency virus became the first HIV-related treatment guideline published by the U.S. Public Health Service in 1989. This report was followed by guideline on prevention of Mycobacterium avium complex (MAC) disease in 1993.
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| ==Treatment== | | ==[[HIV opportunistic infections epidemiology and demographics|Epidemiology and Demographics]]== |
| ===Initiation of ART in the Setting of an Acute OI (Treatment-Naïve Patients)===
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| When an acute OI is present, initiation of ART is usually expected to improve immune function and contribute to faster resolution of the OI.
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| Initiation of ART has been documented to be effective for OIs for which effective therapy does not exist; [[cryptosporidiosis]], [[microsporidiosis]], and [[progressive multifocal leukoencephalopathy ]](PML) might resolve or at least stabilize after the institution of effective ART. For [[kaposi's sarcoma]] (KS), initiation of ART has been documented to lead to resolution of lesions in the absence of specific therapy for the sarcoma.<ref name="pmid11807324">{{cite journal |author=Murdaca G, Campelli A, Setti M, Indiveri F, Puppo F |title=Complete remission of AIDS/Kaposi's sarcoma after treatment with a combination of two nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitor |journal=AIDS |volume=16 |issue=2 |pages=304–5 |year=2002 |month=January |pmid=11807324 |doi= |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0269-9370&volume=16&issue=2&spage=304 |accessdate=2012-04-06}}</ref>
| | ==[[HIV opportunistic infections risk factors|Risk Factors]]== |
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| '''Benefits of ART in preventing OI:'''
| | ==[[HIV opportunistic infections screening|Screening]]== |
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| The initiation of ART in the setting of an acute OI also has preventive benefit; a second OI is less likely to occur if ART is started promptly rather than delaying the initiation of ART.
| | ==[[HIV opportunistic infections natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| '''Disadvantages:'''
| | ==Diagnosis== |
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| Starting ART in the setting of an acute OI has several potential disadvantages.
| | [[HIV opportunistic infections diagnostic criteria|Diagnostic Criteria]] | [[HIV opportunistic infections history and symptoms|History and Symptoms]] | [[HIV opportunistic infections physical examination|Physical Examination]] | [[HIV opportunistic infections laboratory findings|Laboratory Findings]] | [[HIV opportunistic infections electrocardiogram|EKG]] | [[HIV opportunistic infections CT|CT]] | [[HIV opportunistic infections MRI|MRI]] | [[HIV opportunistic infections echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[HIV opportunistic infections other imaging findings|Other Imaging Findings]] | [[HIV opportunistic infections other diagnostic studies|Other Diagnostic Studies]] |
| *Severely ill patients might not absorb ART drugs, leading to subtherapeutic serum levels and the development of antiretroviral drug resistance.
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| *[[Antiretroviral drug#Adverse effects|ART toxicities]] might be confused with disease manifestations or toxicities associated with drugs used for treating patients with an OI. Drug-drug interactions among ART and anti-OI drugs might be difficult to manage.
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| *Renal or hepatic dysfunction during acute OIs might make dosing of ART drugs difficult to estimate.
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| *[[Immune reconstitution inflammatory syndrome|IRIS]] events can occur and cause manifestations that are difficult to distinguish from other clinical conditions.
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| '''When to start the therapy?'''
| | ==Treatment== |
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| For above mentioned reasons, no consensus has been reached concerning the optimal time to start ART in the setting of a recently diagnosed OI. However, one recently completed randomized clinical trial has demonstrated a clinical and survival benefit of starting ART early, within the first 2 weeks, of initiation of treatment for an acute OI, excluding TB.<ref name="pmid9164318">{{cite journal |author=Jacobson MA, Zegans M, Pavan PR, O'Donnell JJ, Sattler F, Rao N, Owens S, Pollard R |title=Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy |journal=Lancet |volume=349 |issue=9063 |pages=1443–5 |year=1997 |month=May |pmid=9164318 |doi=10.1016/S0140-6736(96)11431-8 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(96)11431-8 |accessdate=2012-04-06}}</ref>
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| ===Management of Acute OIs in Patients Receiving ART===
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| OIs that occur after patients have been started on ART can be categorized into three groups.
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| *The '''first group''' includes OIs that occur shortly after initiating ART (within 12 weeks).
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| **These cases might be subclinical infections that have been unmasked by early immune reconstitution or simply OIs that occurred because of advanced immunosuppression and are not considered to represent early failure of ART. Many of these cases represent IRIS.<ref name="pmid12126821">{{cite journal |author=Egger M, May M, Chêne G, Phillips AN, Ledergerber B, Dabis F, Costagliola D, D'Arminio Monforte A, de Wolf F, Reiss P, Lundgren JD, Justice AC, Staszewski S, Leport C, Hogg RS, Sabin CA, Gill MJ, Salzberger B, Sterne JA |title=Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies |journal=Lancet |volume=360 |issue=9327 |pages=119–29 |year=2002 |month=July |pmid=12126821 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673602094114 |accessdate=2012-04-06}}</ref><ref name="pmid9457095">{{cite journal |author=Race EM, Adelson-Mitty J, Kriegel GR, Barlam TF, Reimann KA, Letvin NL, Japour AJ |title=Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease |journal=Lancet |volume=351 |issue=9098 |pages=252–5 |year=1998 |month=January |pmid=9457095 |doi=10.1016/S0140-6736(97)04352-3 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(97)04352-3 |accessdate=2012-04-06}}</ref>
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| **When an OI occurs within 12 weeks of starting ART, treatment for the OI should be started and ART should be continued.
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| *The '''second group''' includes OIs that occur >12 weeks after initiation of ART among patients with suppressed HIV ribonucleic acid. levels and sustained CD4+ counts >200 cells/µL<ref name="pmid11015162">{{cite journal |author=Currier JS, Williams PL, Koletar SL, Cohn SE, Murphy RL, Heald AE, Hafner R, Bassily EL, Lederman HM, Knirsch C, Benson CA, Valdez H, Aberg JA, McCutchan JA |title=Discontinuation of Mycobacterium avium complex prophylaxis in patients with antiretroviral therapy-induced increases in CD4+ cell count. A randomized, double-blind, placebo-controlled trial. AIDS Clinical Trials Group 362 Study Team |journal=Ann. Intern. Med. |volume=133 |issue=7 |pages=493–503 |year=2000 |month=October |pmid=11015162 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=11015162 |accessdate=2012-04-06}}</ref><ref name="pmid10722436">{{cite journal |author=Cinti SK, Kaul DR, Sax PE, Crane LR, Kazanjian PH |title=Recurrence of Mycobacterium avium infection in patients receiving highly active antiretroviral therapy and antimycobacterial agents |journal=Clin. Infect. Dis. |volume=30 |issue=3 |pages=511–4 |year=2000 |month=March |pmid=10722436 |doi=10.1086/313705 |url=http://www.cid.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=10722436 |accessdate=2012-04-06}}</ref> Determining whether these represent a form of IRIS rather than incomplete immunity with the occurrence of a new OI is difficult.
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| **When an OI occurs despite complete virologic suppression (i.e., late OI), therapy for the OI should be initiated and ART should be continued.
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| **If the CD4+ response to ART has been suboptimal, modification of the ART regimen may be considered, although no evidence exists to indicate that changing the ART regimen in this setting will improve the CD4+ response.
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| *The '''third group''' includes OIs that occur among patients who are experiencing virologic and immunologic failure while on ART. These represent clinical failure of ART.
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| **When an OI occurs in the setting of virologic failure, OI therapy should be started, antiretroviral resistance testing should be performed, and the ART regimen should be modified, if possible, to achieve better virologic control.
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| ===Treatment Failure===
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| Clinical failure is defined as lack of improvement or worsening of respiratory function documented by [[arterial blood gases]] (ABGs) after at least 4--8 days of anti-PCP treatment. Treatment failure attributed to treatment-limiting toxicities occurs in up to one third of patients.<ref name="pmid8610948">{{cite journal |author=Safrin S, Finkelstein DM, Feinberg J, Frame P, Simpson G, Wu A, Cheung T, Soeiro R, Hojczyk P, Black JR |title=Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group |journal=Ann. Intern. Med. |volume=124 |issue=9 |pages=792–802 |year=1996 |month=May |pmid=8610948 |doi= |url= |accessdate=2012-04-07}}</ref>
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| ==Special Considerations During Pregnancy==
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| Physiologic changes during pregnancy can complicate the recognition of OIs and complicate pharmacokinetics. Factors to consider include the following:
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| * Increased cardiac output by 30%--50% with concomitant increase in glomerular filtration rate and renal clearance.
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| * Increased plasma volume by 45%--50% while red cell mass increases only by 20%--30%, leading to dilutional anemia.
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| * Tidal volume and pulmonary blood flow increase, possibly leading to increased absorption of aerosolized medications. The tidal volume increase of 30%--40% should be considered if ventilatory assistance is required.
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| * Placental transfer of drugs, increased renal clearance, altered gastrointestinal absorption, and metabolism by the fetus might affect maternal drug levels.
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| * Limited pharmacokinetic data are available; use usual adult doses based on current weight, monitor levels if available, and consider the need to increase doses if the patient is not responding as expected.
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| Also in regards with risk in '''Fetus''', pregnancy should not preclude usual diagnostic evaluation when an OI is suspected.<ref name="pmid15339791">{{cite journal |author= |title=ACOG Committee Opinion. Number 299, September 2004 (replaces No. 158, September 1995). Guidelines for diagnostic imaging during pregnancy |journal=Obstet Gynecol |volume=104 |issue=3 |pages=647–51 |year=2004 |month=September |pmid=15339791 |doi= |url= |accessdate=2012-04-06}}</ref><ref name="pmid10208701">{{cite journal |author=Toppenberg KS, Hill DA, Miller DP |title=Safety of radiographic imaging during pregnancy |journal=Am Fam Physician |volume=59 |issue=7 |pages=1813–8, 1820 |year=1999 |month=April |pmid=10208701 |doi= |url=http://www.aafp.org/link_out?pmid=10208701 |accessdate=2012-04-06}}</ref><ref name="pmid10331526">{{cite journal |author=Adelstein SJ |title=Administered radionuclides in pregnancy |journal=Teratology |volume=59 |issue=4 |pages=236–9 |year=1999 |month=April |pmid=10331526 |doi=10.1002/(SICI)1096-9926(199904)59:4<236::AID-TERA9>3.0.CO;2-6 |url=http://dx.doi.org/10.1002/(SICI)1096-9926(199904)59:4<236::AID-TERA9>3.0.CO;2-6 |accessdate=2012-04-06}}</ref> Experience with use of magnetic resonance imaging (MRI) in pregnancy is limited, but no adverse fetal effects have been noted.<ref name="pmid15339791">{{cite journal |author= |title=ACOG Committee Opinion. Number 299, September 2004 (replaces No. 158, September 1995). Guidelines for diagnostic imaging during pregnancy |journal=Obstet Gynecol |volume=104 |issue=3 |pages=647–51 |year=2004 |month=September |pmid=15339791 |doi= |url= |accessdate=2012-04-06}}</ref>
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| ==Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents==
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| Outline of the Guideline:
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| '''I: [[HIV opportunistic infections#Pneumocystis Pneumonia|Pneumocystis Pneumonia ]]'''
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| *[[HIV opportunistic infections#Preventing Exposure|Preventing Exposure]]
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| *[[HIV opportunistic infections#Preventing Disease|Preventing Disease]]
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| **[[HIV opportunistic infections#Initiating Primary Prophylaxis|Initiating Primary Prophylaxis]]
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| **[[HIV opportunistic infections#Discontinuing Primary Prophylaxis|Discontinuing Primary Prophylaxis]]
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| *[[HIV opportunistic infections#Treatment of Disease|Treatment of Disease]]
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| *[[HIV opportunistic infections#Monitoring and Adverse Events, Including Immune Reconstitution Inflammatory Syndrome (IRIS)|Monitoring and Adverse Events, Including Immune Reconstitution Inflammatory Syndrome (IRIS)]]
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| *[[HIV opportunistic infections#Management of Treatment Failure|Management of Treatment Failure]]
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| *[[HIV opportunistic infections#Preventing Recurrence|Preventing Recurrence]]
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| *[[HIV opportunistic infections#Discontinuing Secondary Prophylaxis (Chronic Maintenance Therapy)|Discontinuing Secondary Prophylaxis (Chronic Maintenance Therapy)]]
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| *[[HIV opportunistic infections#Pneumocystis Pneumonia: Special considerations during pregnancy|Special Considerations During Pregnancy]]
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| '''II: [[HIV opportunistic infections#Toxoplasma gondii Encephalitis|Toxoplasma gondii Encephalitis]]'''
| | [[HIV opportunistic infections medical therapy|Medical Therapy]] | [[HIV opportunistic infections prevention|Prevention]] | [[HIV opportunistic infections cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[HIV opportunistic infections future or investigational therapies|Future or Investigational Therapies]] |
| *[[HIV opportunistic infection toxoplasma gondii encephalitis: prevention and treatment guidelines#Toxoplasma gondii: Preventing Exposure|Preventing Exposure]]
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| *[[HIV opportunistic infection toxoplasma gondii encephalitis: prevention and treatment guidelines#Toxoplasma gondii: Preventing Disease|Preventing Disease]]
| | ==Case Studies== |
| **[[HIV opportunistic infection toxoplasma gondii encephalitis: prevention and treatment guidelines#Toxoplasma gondii: Initiating Primary Prophylaxis|Initiating Primary Prophylaxis]]
| | [[HIV opportunistic infections case study one|Case #1]] |
| **[[HIV opportunistic infection toxoplasma gondii encephalitis: prevention and treatment guidelines#Toxoplasma gondii: Discontinuing Primary Prophylaxis|Discontinuing Primary Prophylaxis]]
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| *[[HIV opportunistic infection toxoplasma gondii encephalitis: prevention and treatment guidelines#Toxoplasma gondii: Treatment of Disease|Treatment of Disease]]
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| *[[HIV opportunistic infection toxoplasma gondii encephalitis: prevention and treatment guidelines#Toxoplasma gondii: Monitoring and Adverse Events|Monitoring and Adverse Events]]
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| ==Related Chapters== | | ==Related Chapters== |