Abstract & Commentarty

Prevention of HIV Infection in Serodiscordant Couples with Early Antiretroviral Therapy

By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.

Dr. Winslow is a speaker for GSK and a consultant for Siemens Diagnostics.

Synopsis: A total of 1,763 couples serodiscordant for HIV-1 infection were enrolled in this prospective trial. HIV-1-infected patients with CD4+ lymphocyte counts between 350 and 500 cells/mL were randomized to receive either immediate therapy or have antiretroviral therapy deferred until either onset of HIV-related symptoms or decline in CD4+ count. At the time of this analysis, 39 HIV-1 transmissions were observed and 28 were virologically linked to the infected partner. Of these, only 1 occurred in the early therapy group..

Sources: Cohen MS, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011 July 18; Epub ahead of print.

A total of 1,763 HIV-1 serodiscordant couples in nine countries with the infected partner having CD4+ counts of 350-500/mL were randomized 1:1 to early (immediate) vs. delayed (CD4+ had declined to ≤ 250/mL or after development of an AIDS-related illness) antiretroviral therapy of the infected partner. Fifty-four percent of the subjects were from Africa; 50% of the infected partners were men; 97% of couples were heterosexual; and 94% were married.

As of February 2011, after a median follow-up of 1.7 years, a total of 39 HIV-1 transmissions were observed. Sequencing of the pol genes from linked cases showed that 28 were virologically linked to the infected partner. Of these linked transmissions, only 1 occurred in the early therapy group. Early antiretroviral therapy also resulted in fewer primary clinical endpoints (occurrence of pulmonary TB, severe bacterial infections, a WHO stage 4 event or death) in the HIV infected partners.

Commentary

This is a very important study, which conclusively shows that early initiation of antiretroviral therapy reduces transmission of HIV-1 in serodiscordant couples. Consistent with previous studies, high viral load at baseline predicted HIV-1 transmission. In the early treatment group, 89% of patients had plasma HIV RNA < 400 copies/mL after 3 months of treatment. The study has obvious direct relevance to HIV prevention efforts and, even in the absence of formal cost-benefit analyses, provides additional justification for universal implementation of early antiretroviral therapy in the developing world.