Editorial
Antiretroviral Treatment as Prevention
N Engl J Med 2011; 365:561-562August 11, 2011
- Article
The numbers that define the scope of the HIV–AIDS pandemic are staggering: 30 years, 60 million infections, 30 million deaths. We have not been defenseless in this fight, however. The introduction of potent combination antiretroviral therapy in 1996 and the public health approach to HIV treatment in resource-limited settings in 2002 have changed the course of the epidemic.1,2
In parallel with treatment, the use of antiretroviral drugs as a prevention tool has been a focus from the beginning of the antiretroviral-therapy era, with the hallmark achievement being the prevention of mother-to-child transmission of the virus. The result has been the virtual elimination of neonatal HIV-1 infection in resource-rich settings. Sadly, this intervention in its most effective form reaches only a minority of HIV-infected pregnant women in resource-limited settings.3,4
In this issue of the Journal, Cohen et al.5 describe the results of the HIV Prevention Trials Network (HPTN) 052 study, which has now provided definitive proof that (as suggested by the findings of previous cohort studies6) antiretroviral treatment reduces the rate of sexual transmission of HIV-1. This multinational study enrolled 1763 discordant couples, in whom the HIV-1–infected partner had a CD4 count between 350 and 550 cells per cubic millimeter. The HIV-1–positive partners were randomly assigned to receive early antiretroviral therapy (in which therapy was started at enrollment) or delayed antiretroviral therapy, in which therapy was initiated when the CD4 count dropped below 250 cells per cubic millimeter or an HIV-1–related event occurred. The study posed two questions: Would antiretroviral treatment of the HIV-1–positive partner reduce the rate of transmission to the negative partner, and would immediate therapy slow disease progression in the HIV-1–infected index patient, as compared with delayed therapy?
The answer to the first question was a resounding yes. Of a total of 39 HIV-1 transmission events, 28 were genetically linked, as determined by viral sequence analysis. Of the 28 linked transmissions, only 1 occurred in the early-therapy group, whereas 27 occurred in the delayed-therapy group, resulting in a 96% reduction in the rate of transmission. Of these 27 transmissions, 9 were man-to-woman, 18 were woman-to-man, and all occurred when the infected partner was not receiving antiretroviral therapy.
The answer to the second question, whether early therapy would reduce the rate of disease progression in the HIV-1–infected index cases, was a more muted, but still definite, yes. A total of 105 participants had at least one clinical end point: 40 in the early-therapy group and 65 in the delayed-therapy group, for a reduction of nearly 40% in the progression of HIV-1–related disease. Extrapulmonary tuberculosis dominated the clinical events and drove the between-group difference (3 cases vs. 17 cases).
As with any initial report of a major clinical trial, questions remain. Will the pending data with respect to viral genotyping shed light on the one transmission that had not yet been analyzed or on the three transmissions that were indeterminately linked? What are the viral and host factors that explain why transmission events occurred largely in Africa? Would isoniazid treatment of latent tuberculosis have eliminated the statistical difference in the treatment end point that was driven by extrapulmonary tuberculosis? How generalizable are these results? Answers to these questions and others will emerge through further analyses of the data from the HPTN 052 study and subsequent trials.
Drugs to prevent HIV-1 transmission are being investigated in both infected and uninfected persons. In HIV-1–negative persons, drugs can be used before or after high-risk exposure (or both). The use of 1% tenofovir topical gel as a microbicide in women7 and of oral combination therapy with tenofovir and emtricitabine in men who have sex with men8 has reduced rates of HIV-1 acquisition by 39% and 44%, respectively, findings that have provided strong encouragement for these approaches.
In HIV-1–positive persons, the use of antiretroviral agents to prevent secondary transmission has led to a variety of proposed test-and-treat strategies.1,9 The dovetailing of individual and public health benefits that are suggested by the findings of the HPTN 052 study provides a major impetus for these initiatives to move forward.
Antiretroviral therapy is by no means perfect and is not the ultimate answer to controlling and ending the HIV epidemic. Adverse events, emergence of drug-resistant viral strains, maintenance of adherence, sustainability, and cost are just some of the concerns. However, this is precisely the wrong time to limit access to antiretroviral therapy in resource-limited settings, since we have the tools in hand to maintain or restore health in infected persons and reduce transmission to their sexual partners.
Aggressive programs to diagnose and treat HIV infection as part of a comprehensive care package and multiple approaches to the prevention of transmission that have been tested in well-designed clinical trials have the potential to preserve health and control the epidemic until a safe and effective HIV vaccine is a reality.
Disclosure forms provided by the author are available with the full text of this article at NEJM.org.
This article (10.1056/NEJMe1107487) was published on July 18, 2011, at NEJM.org.
Source Information
From the Division of Infectious Diseases, Columbia University Medical Center, New York–Presbyterian Hospital, New York.
- References
References
1
Dieffenbach CW ,Fauci AS . Thirty years of HIV and AIDS: future challenges and opportunities. Ann Intern Med 2011;154:766-771
Medline2
Gilks CF ,Crowley S ,Ekpini R , et al. The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings. Lancet 2006;368:505-510
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Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. May 24, 2010. (http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf.)
4
World Health Organization. PMTCT strategic vision 2010-2015: preventing mother-to-child transmission of HIV to reach the UNGASS and Millennium Development Goals. (http://www.who.int/hiv/pub/mtct/strategic_vision.pdf.)
5
Cohen MS ,Chen YQ ,McCauley M , et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011;365:493-505
Full Text | Web of Science | Medline6
Donnell D ,Baeten JM ,Kiarie J , et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 2010;375:2092-2098
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Abdool Karim Q ,Abdool Karim SS ,Frohlich JA , et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010;329:1168-1174
CrossRef | Web of Science | Medline8
Grant RM ,Lama JR ,Anderson PL , et al. Pre-exposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010;363:2587-2599
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Granich RM ,Gilks CF ,Dye C ,De Cock KM ,Williams BG . Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet 2009;373:48-57
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- Citing Articles (3)
Citing Articles
1
Gabriela Paz-Bailey, Virginia Isern Fernandez, Sonia Morales Miranda, Jerry O. Jacobson, Suyapa Mendoza, Mayte A. Paredes, Damien C. Danaval, David Mabey, Edgar Monterroso. (2012) Unsafe Sexual Behaviors Among HIV-Positive Men and Women in Honduras: The Role of Discrimination, Condom Access, and Gender. Sexually Transmitted Diseases 39:1, 35-41
CrossRef2
Carl W. Dieffenbach. (2012) Preventing HIV transmission through antiretroviral treatment-mediated virologic suppression. Current Opinion in HIV and AIDS1
CrossRef3
Jeffrey H. Herbst, Marlene Glassman, James W. Carey, Thomas M. Painter, Deborah J. Gelaude, Amy M. Fasula, Jerris L. Raiford, Arin E. Freeman, Camilla Harshbarger, Abigail H. Viall, David W. Purcell. (2012) Operational Research to Improve HIV Prevention in the United States. JAIDS Journal of Acquired Immune Deficiency Syndromes1
CrossRef
