A large clinical trial conducted by the international HIV Prevention Trials Network (HPTN) confirms that treating HIV-positive people with antiretroviral (ARV) drugs reduces the risk of transmitting the virus to HIV-negative sexual partners by 96 percent—at least among heterosexual couples—according to data from the study reported Monday, July 18, at the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention in Rome. The full results follow a May 2011 announcement heralding the study's preliminary findings.
The study, known as HPTN 052, was designed to evaluate whether immediate versus delayed use of ARV therapy by people living with HIV would reduce transmission of HIV to their negative partners. The study also set out to determine the potential health benefits of early therapy among the HIV-positive partners; those results were also presented at the conference and have been reported by AIDSmeds/POZ separately.
According to Myron Cohen, MD, of the University of North Carolina at Chapel Hill, who presented his team's findings in Rome, there is “extensive biological plausibility” for ARV treatment to work as an HIV prevention modality. Studies have found that concentrations of HIV in the blood and genital secretions correlate with sexual transmission, he explained, and that ARV agents that penetrate the genital tract can reduce viral loads in those compartments.
Cohen also noted that several observational studies have shown that ARV treatment reduces transmission of HIV in serodiscordant couples, in which one partner is positive and the other is negative. Yet data from prospective clinical trials—in which serodiscordant couples are actively followed under controlled circumstances to look for HIV transmission—have been limited.
Cohen's group enrolled 1,763 sexually active, HIV-serodiscordant couples. All but one of the study couples were heterosexual male and female couples.
All of the HIV-positive participants had to have a CD4 count between 350 and 550 upon entering the study. After the study began, 886 HIV-positive participants were randomized to start ARV therapy right away (the immediate treatment group), whereas 877 waited until their CD4s dropped to 250 or they developed an AIDS-related illness (the delayed treatment group).
Throughout the study, volunteers in both groups received HIV-related care that included counseling on safe-sex practices, free condoms, treatment for sexually transmitted infections (STIs), regular HIV testing and frequent evaluation and treatment for any complications related to HIV. Each group received the same amount of care and counseling. Any HIV-negative person who contracted the virus during the study was referred to local services for appropriate medical care and treatment.
The primary goal of the study was to look for virologically linked transmission events. To accomplish this, the researchers conducted genetic analyses to confirm that the source of any new infection was the HIV-positive partner in the study.
Overall, 278 couples were enrolled at sites in the Americas, notably the United States (2 couples) and Brazil (276 couples); 954 couples were enrolled in Africa, and 531 were enrolled in Asia.
Roughly half of all HIV-positive partners in the study were men, and about 94 percent of the couples enrolled were married. The average age upon entering the study was 32, and about 8 percent reported having unprotected intercourse. Average CD4 counts were relatively high among the HIV-positive partners in the immediate and delayed treatment groups: 442 and 428, respectively.
HPTN 052 was originally scheduled to continue until 2015. An early look at the data by the data safety monitoring board (DSMB), however, found that those in the early treatment group were much less likely than those in the delayed treatment group to transmit HIV to their partners and, thus, it would be unnecessary to continue to the trial.
While the early termination of the study satisfied ethical concerns, Cohen noted that the average follow-up period was only 1.7 years, which ultimately prevents an evaluation of the long-term efficacy of ARV treatment for prevention purposes.
There were 39 new HIV infections among the HIV-negative participants, 28 of which could be traced directly between the HIV-positive study participants and their HIV-negative partners, Cohen reported. Eleven new HIV infections could not be readily linked to the HIV-positive partners in the study.
Of the 28 new infections, 27 occurred in the delayed treatment group, compared with just one in the early treatment group—a 96 percent reduction in new infections. This difference was highly statistically significant, meaning that it was too great to have occurred by chance.
Viral load proved to be the most important predictor of transmission in both groups. The lower the viral load, Cohen pointed out, the lower the risk of infection among the serodiscordant couples.
Cohen noted that 82 percent of the transmissions occurred in sub-Saharan Africa. He also pointed out the 64 percent of the transmissions were from HIV-positive females to their HIV-negative male partners.
Of particular interest to Cohen's group was the finding that most transmissions occurred when the HIV-positive partner had a CD4 count above 350. This is notable, HIV treatment is only recommended for those with fewer than 350 CD4s in many of the countries participating in HPTN 052.
Sexual behavior was not found to be different between the two groups, with similar rates of pregnancy, STIs, sexual activity and condom use among those HIV-positive individuals who initiated therapy immediately and their partners, compared with those who delayed therapy and their partners.
Focusing specifically on the one HIV transmission that occurred in the immediate treatment group, Cohen noted that the HIV-negative partner tested positive for the virus—using standard Western blot testing—on day 85 of the study, whereas the HIV-positive partner's first undetectable viral load was documented 28 days after entering the study. The researchers believe that the HIV-negative partner was infected at least 50 days before testing positive, likely 84 to 190 days earlier. In other words, the HIV-negative partner was likely infected with the virus before the HIV-positive partner was able to achieve an undetectable viral load while on treatment.
In conclusion, Cohen reiterated that early ARV therapy that suppresses viral replication led to a 96 percent reduction of sexual transmission of HIV in serodiscordant couples.