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Antiretroviral Treatment of Adult HIV Infection 2010 Recommendations of the International AIDS Society–USA Panel

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Antiretroviral Treatment of Adult HIV Infection 2010 Recommendations of the International AIDS Society–USA Panel REVIEW CLINICIAN’S CORNER Antiretroviral Treatment of Adult HIV Infection 2010 Recommendations of the International AIDS Society–USA Panel Melanie A. Thompson, MD Context Recent data regarding the consequences of untreated human immunodefi- Judith A. Aberg, MD ciency virus (HIV) infection and the expansion of treatment choices for antiretroviral- Pedro Cahn, MD naive and antiretroviral-experienced patients warrant an update of the International AIDS Society–USA guidelines for the use of antiretroviral therapy in adults with HIV infection. Julio S. G. Montaner, MD Objectives To provide updated recommendations for management of HIV- Giuliano Rizzardini, MD infected adults, using antiretroviral drugs and laboratory monitoring tools available in Amalio Telenti, MD, PhD the international, developed-world setting. This report provides guidelines for when to initiate antiretroviral therapy, selection of appropriate initial regimens, patient moni- Jose´ M. Gatell, MD, PhD toring, when to change therapy, and what regimens to use when changing. Huldrych F. Günthard, MD Data Sources and Study Selection A panel with expertise in HIV research and Scott M. Hammer, MD clinical care reviewed relevant data published or presented at selected scientific con- Martin S. Hirsch, MD ferences since the last panel report through April 2010. Data were identified through a PubMed search, review of scientific conference abstracts, and requests to antiret- Donna M. Jacobsen, BS roviral drug manufacturers for updated clinical trials and adverse event data. Peter Reiss, MD, PhD Data Extraction and Synthesis New evidence was reviewed by the panel. Rec- Douglas D. Richman, MD ommendations were drafted by section writing committees and reviewed and edited by the entire panel. The quality and strength of the evidence were rated and recom- Paul A. Volberding, MD mendations were made by full panel consensus. Patrick Yeni, MD Conclusions Patient readiness for treatment should be confirmed before initiation of Robert T. Schooley, MD antiretroviral treatment. Therapy is recommended for asymptomatic patients with a CD4 cell count Յ500/µL, for all symptomatic patients, and those with specific conditions and UCCESSFUL ANTIRETROVIRAL comorbidities. Therapy should be considered for asymptomatic patients with CD4 cell therapy (ART) is associated with count Ͼ500/µL. Components of the initial and subsequent regimens must be individu- dramatic decreases in AIDS- alized, particularly in the context of concurrent conditions. Patients receiving antiretro- defining conditions and their as- viral treatment should be monitored regularly; treatment failure should be detected and Ssociated mortality. Expansion of treat- managed early, with the goal of therapy, even in heavily pretreated patients, being HIV-1 ment options and evolving knowledge RNA suppression below commercially available assay quantification limits. require revision of guidelines for the ini- JAMA. 2010;304(3):321-333 www.jama.com tiation and long-term management of ART in adults with HIV infection. Analyses of clinical trials and epide- appointed by International AIDS Society– Since the 2008 International AIDS miologic cohorts have shed light on the USA according to clinical and research Society–USA ART guidelines,1 new data role of ART in mitigating serious non- expertise. Current panel members do not have emerged regarding timing of AIDS events associated with uncon- participate in pharmaceutical market- therapy, optimal regimen choices, and trolled HIV replication. Newer drugs are ing or promotional activities (eg, speak- monitoring. There are also issues of spe- better understood in terms of efficacy, ers’ bureaus, industry satellites) during cial relevance to circumstances such as toxicity, and potential uses. New data tenure on the panel. The current panel pregnancy, hepatitis virus coinfec- also suggest a role for ART in the pre- convened in January 2010 and met tions, kidney disease, cardiovascular vention of HIV transmission. weekly in person or by teleconference. disease, and primary HIV infection. Data published or presented in specific METHODS scientific meetings since the last report1 The panel was convened in 1995 to de- CME available online at velop evidence-based recommenda- Author Affiliations are listed at the end of this article. www.jamaarchivescme.com tions for ART for HIV-infected adults in Corresponding Author: Melanie A. Thompson, MD, and questions on p 357. 131 Ponce de Leon Ave NE, Ste 130, Atlanta, GA developed-world settings.2 Members are 30308 ([email protected]). ©2010 American Medical Association. All rights reserved. (Reprinted) JAMA, July 21, 2010—Vol 304, No. 3 321 Downloaded From: http://jama.jamanetwork.com/ on 07/20/2012 ANTIRETROVIRAL TREATMENT OF ADULT HIV INFECTION were considered (eFigure, available at ing in end-organ damage and comorbid nized as reasons to initiate ART regard- http://www.jama.com). Data on file and conditions not previously thought to be less of CD4 cell count.1 Older age is also personal communications were not con- associated with HIV infection. Several associated with higher risk of AIDS and sidered except for data and safety moni- studies have shown that the life span of non-AIDS-related deaths. Pregnant toring board reports and US Food and those with HIV infection still falls short women should be treated at least by the Drug Administration alerts. of that of the general population, even second trimester and therapy contin- For identification of evidence, one at higher CD4 cell counts.3-6 This life span ued after birth.5,10,14-18 member (P.A.V.) conducted a PubMed decrease is related to serious, non-AIDS search of reports published since the last events attributed to chronic immune ac- Special Considerations update. Search terms were HIV and an- tivation and the potentially permanent HIV increases the risk of liver-related tiretroviral, limited to humans, clinical immune damage associated with pro- mortality in those with hepatitis B virus trials, meta-analyses, randomized con- longed immune depletion. In several data (HBV).19 Hepatitis B infection should not trolled trials, reviews, English, and adult, sets,3-8 non-AIDS events were associ- be treated with lamivudine or emtricit- and yielded 582 citations. Of those, 194 ated with elevated levels of viral repli- abine alone. If tenofovir is contraindi- citations were selected for review, elimi- cation and markers of immune activa- cated, entecavir should be added.20 The nating those not relevant to adult care in tion and coagulation (including D-dimer, durability of entecavir is compromised resource-rich settings. Section teams interleukin 6, or high-sensitivity C- by previous HBV treatment failure with identified abstracts from scientific con- reactive protein). Mortality from non- regimens including emtricitabine or la- ferences. Drug manufacturers were asked AIDS events now exceeds that of AIDS- mivudine.21 Flares of hepatocellular in- to provide published or presented data defining opportunistic diseases in flammation may occur when therapy on updated clinical trials and adverse individuals receiving effective ART.9-11 with agents active against HBV is dis- events for their products. The strength of evidence support- continued or when HBV resistance to la- Section team leaders (J.A.A., P.C., ing initiation of therapy increases as mivudine or emtricitabine emerges in pa- J.S.G.M., G.R., and A.T.) summarized CD4 cell count decreases. In a cohort tients receiving these agents without section consensus for group review and of 17 517 asymptomatic HIV-infected tenofovir or entecavir.22,23 If ART must discussion. The quality and strength persons, initiating ART at a CD4 cell be interrupted, patients should be closely of the evidence were rated for each count greater than 500/µL decreased monitored for HBV reactivation.24 recommendation (eBox). Final recom- mortality by 94%, and initiating it at a Patients with HIV–hepatitis C virus mendations were by full panel consensus. CD4 cell count between 351 and 500/µL (HCV) coinfection progress to end- decreased mortality by 69%, although stage liver disease more rapidly than do WHEN TO START the numbers of deaths were low in both HCV monoinfected patients.25 Clear- Established HIV-1 Infection groups. The majority of deaths were ance of HCV is associated with regres- Deciding to start ART requires weigh- from non-AIDS conditions.10 In an sion of liver fibrosis and a reduced risk ing the benefits of treatment on mor- analysis of 62 760 persons in 12 co- of ART-related hepatotoxicity.26 In one bidity and mortality against its risks, in- horts, reduction in death was 23% and study, abacavir with ribavirin was as- cluding toxicity, resistance, drug 45% for those beginning therapy with sociated with a reduced rate of sus- interactions, and the costs and incon- a CD4 cell count greater than 500/µL tained HCV virologic response.27 Zido- venience of lifelong treatment. Sus- and 350 to 500/µL, respectively.12 vudine, didanosine, and stavudine have tained viral suppression restores and Data from prospective observational overlapping hematologic and hepatic preserves immunologic function, de- cohorts and clinical trials demonstrate toxicities with current HCV therapy.25 creasing opportunistic diseases and worse outcomes among patients who be- Patients with HCV coinfection are at in- mortality. The patient must be ready gin receiving ART at CD4 cell counts less creased risk of hepatotoxicity, and cer- and willing to adhere to lifelong than 350/µL or who have symptomatic tain ART regimens may require dose ad- therapy. Advances in ART continue to HIV disease.1 Among 24 444 patients justment (see “Monitoring” section). shift the therapeutic risk-benefit bal- from 18 cohorts, there was no addi- Current HCV therapy has a higher ance to earlier treatment. Improve- tional benefit from initiating therapy at probability of sustained HCV viro- ments in potency, toxicity and toler- CD4 cell counts of 451 to 550/µL com- logic response with HCV genotype 2 or ability, and pill burden allow for durable pared with 351 to 450/µL. However, this 3; therefore, for patients with a high viral suppression for most patients.
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