Ending the HIV–AIDS Pandemic — Follow the Science

published on December 2, 2015 by Anthony S. Fauci, M.D., and Hilary D. Marston, M.D., M.P.H., in The New England Journal of Medicine

In July 1996, researchers, policymakers, and activists involved in the fight against HIV–AIDS met in Vancouver, Canada, for the 11th International Conference on AIDS. During that historic meeting, practitioners and patients heard evidence regarding a powerful weapon to stop the relentless onslaught of the human immunodeficiency virus (HIV): combination antiretroviral therapy (ART), with a protease inhibitor as the centerpiece of the regimen. In the nearly 20 years since that watershed meeting, the early promise of durable effects from combination therapy has been realized for many patients: between 2000 and 2014, the rollout of ART saved an estimated 7.8 million lives worldwide.

Despite this success, the timing of ART initiation has remained the subject of intense debate. As with any therapy, clinicians and their patients weighed ART's benefits against its risks, and the results of that calculus seemed to depend on the patient's stage of illness. Specifically, evidence supporting treatment later in the course of HIV infection, when the CD4+ T-cell count fell below a certain critical level, seemed far stronger than that supporting early treatment (particularly given the toxic effects associated with the first approved antiretroviral drugs). Today, a series of well-designed efficacy studies conducted over a period of more than a decade has fundamentally changed this discussion.

In addition, researchers continue to accrue promising data on the concept of using ART for HIV prevention in HIV-negative persons — preexposure prophylaxis (PrEP). Findings from the landmark Intervention Préventive de l'Exposition aux Risques avec et pour les Gays (IPERGAY) study, now reported in the Journal (pages 2237–2246), demonstrate the safety and efficacy of “on-demand” PrEP for men who have sex with men and transgender women (persons who are born male but identify as female), who are at high risk for HIV infection. In this study, persons who took PrEP in an event-driven manner around the time of sexual activity were 86% less likely to acquire HIV infection than those taking placebo.

Taken together, these studies have shown definitively that the benefits of prompt initiation of ART — regardless of the CD4+ T-cell count — outweigh the risks, for both the infected person and uninfected sexual partners and that PrEP can be implemented in a way that is both acceptable to patients and safe and effective in blocking HIV transmission.

With regard to ART initiation, three critical questions were asked and answered by a “trifecta” of large international randomized, controlled trials over the course of a decade. First, practitioners, including ourselves, and patients had worried about the risks of toxic effects of long-term ART, particularly on the cardiovascular system, and wondered whether long-term treatment was worse than the virus itself for some patients. Moreover, practical concerns about the cost and inconvenience of ART loomed large, as did the related risks of poor adherence and the potential emergence of resistant virus.

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Ending the HIV–AIDS Pandemic — Follow the Science

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