Emma Hitt

July 19, 2011

July 19, 2011 (Rome, Italy) — Early initiation of antiretroviral therapy (ART) reduced rates of sexual transmission of HIV-1 and clinical events in couples in which one partner was HIV-1-positive and the other was HIV-1-negative, according to new findings from the HIV Prevention Trials Network (HPTN) 052 Study Team.

The findings coincide with reports from the TDF2 and Partners PrEP studies suggesting that ART can dramatically reduce transmission of HIV-1 from infected to uninfected partners.

Myron Cohen, MD, from the University of North Carolina at Chapel Hill, presented the findings for the HPTN 052 study here at the 6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.

Dr. Cohen's presentation was met with a rare standing ovation from audience members. The findings were also published online July 18 in The New England Journal of Medicine.

HPTN 052 researchers sought to compare early vs delayed antiretroviral therapy in patients with HIV-1 infection who had CD4 counts between 350 and 550 cells/mm3 and who were in a stable sexual relationship with a partner who was not infected.

A total of 1763 HIV-1 serodiscordant couples at 13 sites in 9 countries were included in the analysis. Just more than half of the participants were from Africa, and 50% of infected partners were men. Patients were randomly assigned to receive therapy either immediately or after CD4 cell counts had dropped to 250 cells/mm3 or less or HIV-1-related symptoms had occurred. Study drugs included lamivudine/zidovudine, efavirenz, atazanavir, nevirapine, tenofovir, lamivudine, zidovudine, didanosine, stavudine, lopinavir/ritonavir, ritonavir, and emtricitabine/tenofovir.

A total of 39 HIV-1 transmissions were observed during the study, indicating an incidence rate of 1.2/100 person-years (95% confidence interval [CI], 0.9 - 1.7). Of the 39 HIV-1 transmissions, 28 were virologically linked to the infected partner, indicating an incidence rate of 0.9/100 person-years (95% CI, 0.6 - 1.3). The remaining 11 infections were not linked to the study partner.

Of the linked transmissions, only 1 occurred in the early-therapy group compared with 27 in the late-therapy group (hazard ratio, 0.04; 95% CI, 0.01 - 0.27; P < .001), suggesting a strong benefit for the early initiation of antiretroviral therapy. In addition, participants receiving early therapy had fewer treatment endpoints (hazard ratio, 0.59; 95% CI, 0.40 - 0.88; P = .01).

"We now know that early initiation of antiretroviral therapy prevents the linked transmission of HIV," Dr. Cohen said in a summary session after his talk. "We know also that early antiretroviral therapy reduced the number of clinical events observed, and this further strengthens the argument for when discussion of therapy should be initiated."

According to Dr. Cohen, this study is definitive proof of the concept that early therapy can help prevent transmission. "We proved that, and we're pleased with that," he said.

Beatrice Grinsztejn, MD, from the Oswaldo Cruz Foundation, Instituto de Pesquisa Clínica Evandro Chagas, in Rio de Janeiro, Brazil, presented data on the trial's clinical outcomes at the same session, reporting a 41% reduction in HIV-1-related clinical events.

"ART not only prevented transmissions but also benefited the person taking the drugs," Dr. Grinsztejn told Medscape Medical News. According to Dr. Grinsztejn, the incidence rates of tuberculosis were almost double in the delayed-therapy group compared with in the immediate-treatment group (1.9/100 person-years vs 1.0/100 person-years).

She added that ART therapy was well-tolerated in this wide range of high-CD4 population, with low rates of serious lab abnormalities and adverse events. "No apparent difference was observed in the time to death in the delayed arm compared to the immediate arm," she said.

In a related editorial, also published online July 18 in The New England Journal of Medicine, Scott M. Hammer, MD, from the Division of Infectious Diseases, Columbia University Medical Center, New York–Presbyterian Hospital, New York City, notes that 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 women and of oral combination therapy with tenofovir and emtricitabine in men who have sex with men has reduced rates of HIV-1 acquisition by 39% and 44%, respectively, findings that have provided strong encouragement for these approaches," he writes.

Last week, results from 2 additional clinical trials of preexposure prophylaxis for HIV prevention among heterosexuals were presented at a press conference held by the US Centers for Disease Control and Prevention (CDC).

The CDC's Michael Thigpen, MD, principal investigator of the TDF2 study, conducted in partnership with the Botswana Ministry of Health, found that a once-daily tablet containing tenofovir/emtricitabine reduced the risk of acquiring HIV infection by 63% overall among heterosexual men and women. Results from the study were also presented in today's session at IAS.

Also at the CDC press conference, the University of Washington's Partners PrEP study found that 2 separate regimens, tenofovir and tenofovir/emtricitabine, significantly reduced HIV transmission (by 62% and 73%, respectively) among heterosexual couples in which one partner is infected with HIV and the other is not.

The HTPN 052 study was not commercially supported. Study drugs were donated by Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, and Merck. Author and editorialist disclosures are available at NEJM.org.

6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstracts MOAX0102, MOAX0105. Presented July 18, 2011.

N Engl J Med. Published online July 18, 2011. Article full text, Editorial full text

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