This report is part of a 12-month Clinical Context series. By Michael Smith, North American Correspondent, MedPage Today Published: May 26, 2010 Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston. Earn CME/CE credit for reading medical news Action Points * Explain to interested patients that this study found that HIV treatment was associated with a markedly reduced rate of transmission between members of couples where one member was infected and the other not. Antiretroviral treatment appears to reduce the risk that an HIV-positive person will pass the virus to his or her uninfected partner, researchers said. In a prospective cohort analysis, the risk of transmission between members of discordant couples was reduced by 92% with HIV treatment, according to Deborah Donnell, PhD, of the University of Washington in Seattle, and colleagues. Most transmissions in the cohort occurred when the infected partner had a high viral load of more than 50,000 copies of viral RNA per milliliter of plasma, Donnell and colleagues reported online in The Lancet. The finding is additional evidence that antiretroviral treatment has a powerful effect on prevention, according to Franois Dabis, MD, PhD, of the Universit Victor Segalen in Bordeaux, France, and colleagues, who were not involved the study. Writing in an accompanying comment article, they said researchers and public health authorities "should not wait" for more studies before starting trials of the so-called test-and-treat strategy, in which whole populations are tested and antiretroviral therapy is offered to all those found to be HIV-positive, regardless of their immune status and viral load. "Today's results argue powerfully for a new generation of research on HIV prevention at the population level," Dabis and colleagues argued. The findings by Donnell and colleagues come from a prospective substudy, nested within a large randomized trial that tested whether treating herpes simplex virus type 2 in men and women coinfected with that virus and HIV would reduce the risk of transmitting HIV to an HIV-negative heterosexual partner. The major study, conducted in Africa, found no reduction in transmission of HIV, although benefits of treating the herpes virus were seen. (See Herpes Therapy Doesn't Bar HIV Transmission) For that study, the HIV-positive participants had to have a serum CD4 cell count higher than 250 cells per microliter at the start, but if their CD4 count fell below national guidelines, they were started on antiretroviral therapy. The trial included 3,381 couples at a median CD4 cell count of 198, including 349 participants with HIV who started therapy during the study, Donnell and colleagues said. Overall, there were 103 HIV transmissions between partners that were confirmed by genetic analysis of the virus in both partners. Of those, only one occurred in a couple in which the infected partner had started treatment. That corresponds to transmission rates of 0.37 per 100 person-years in those under treatment and 2.24 per 100 person-years in those who had not started therapy. The adjusted incidence rate ratio was 0.08 -- a 92% reduction -- which was significant at P=0.004. The researchers also found that -- among participants not on treatment -- the highest HIV-1 transmission rate (8.79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per microliter. Nonetheless, 94 transmissions took place in couples where the untreated HIV-positive partner had a CD4 cell count greater than 200 cells. Among that group, 70% of transmissions occurred when plasma HIV was higher than 50,000 copies of viral RNA per milliliter. Donnell and colleagues argued that low CD4 counts and high plasma HIV concentrations might guide the use of antiretroviral treatment for prevention purposes. Treatment "could be an effective strategy" to prevent HIV transmission at the population level, they said. Within the cohort, they said, there was no evidence that starting antiretroviral therapy led to changes in sexual behavior that might increase the risk of transmission. They cautioned that information about starting therapy was obtained by self-report, yielding a possibility that time exposed to medications might be misclassified. However, they said, in the single case in that setting, the transmission appears to have occurred after the start of treatment. They also noted that they had no data about adherence to therapy, although 70% of participants on treatment had substantial reductions in plasma HIV concentrations. The study was supported by the Bill & Melinda Gates Foundation and the NIH. Donnell reported no competing interests. The editorial writers said they had no conflicts. Primary source: The Lancet Source reference: Donnell D, et al "Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis" Lancet 2010; DOI:10.1016/S0140-6736(10)60705-2. Additional source: The Lancet Source reference: Dabis F, et al "HIV drugs for treatment, and for prevention" Lancet 2010; DOI:10.1016/S0140-6736(10)60838-0.