Editors' ChoiceInfectious Disease

Preventing HIV Transmission: Early Therapy Is Key

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Science Translational Medicine  27 Jul 2011:
Vol. 3, Issue 93, pp. 93ec117
DOI: 10.1126/scitranslmed.3002933

More than 34 million people are living with HIV worldwide. Sexual transmission accounts for 80% of new HIV infections, so preventing this route of transmission is critical for curtailing the pandemic. Now, Cohen and colleagues demonstrate that early initiation of combination antiretroviral therapy for couples serodiscordant for HIV infection reduces the likelihood of HIV transmission to the uninfected partner and reduces the number of HIV-related clinical events.

In this multicontinent, randomized, controlled trial (called HPTN 052), the investigators enrolled 1763 couples who were identified as serodiscordant for HIV infection (one partner was infected, and the other was not). Couples were then randomized so that the HIV-infected partner received combination antiretroviral therapy either immediately (early) or after a decrease in their CD4 T cell counts or the appearance of other HIV-related symptoms (delayed). Couples were followed monthly for the first 3 months then quarterly thereafter, and specific study endpoints were measured, including HIV infection in the uninfected partner and World Health Organization stage 4 clinical events such as severe bacterial infection, pulmonary tuberculosis, or death. To assess whether new HIV cases were linked to the infected partner, DNA sequences containing the HIV polymerase gene from both partners were amplified and compared.

886 HIV serodiscordant couples were randomly assigned to early combination antiretroviral therapy; 877 couples received delayed treatment. The majority of couples (97%) were heterosexual and between the ages of 26 and 40 (67%). After a median followup time of 1.7 years, Cohen and colleagues found a total of 39 new HIV cases, 28 of which could be clearly linked genetically to the HIV-infected partner. Only one person in the early therapy group was newly infected, compared with 27 individuals in the delayed therapy group. Using Cox proportional hazards analysis and correcting for differences in baseline CD4 T cell counts, viral load, gender, and condom use, the decrease in HIV transmission in the early therapy arm represented a relative reduction of 96% in new, linked HIV infections. Similarly, individuals in the early therapy group showed a 41% decrease in HIV-related clinical events, suggesting that they remained healthier over the course of the study. The authors do note that more adverse clinical events occurred in the early therapy group related to drug treatment, but the long-term implications of this finding are not yet clear. This study adds considerable evidence to support early treatment of HIV-infected persons in serodiscordant relationships to both decrease virus transmission and improve the health of those infected with HIV.

M. S. Cohen et al., Prevention of HIV-1 infection with early antiretroviral therapy. N. Engl. J. Med. 18 July 2011 (10.1056/NEJMoa1105243). [Abstract]

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