Jim Kling

March 07, 2012

March 7, 2012 (Seattle, Washington) — The partners of men and women infected with HIV-1 who were treated prophylactically with once-daily oral tenofovir or combination emtricitabine/tenofovir were at reduced risk for infection, according to a study presented here at the 19th Conference on Retroviruses and Opportunistic Infections.

The researchers conducted a randomized trial of 4758 heterosexual couples from Kenya and Uganda. In each participating pair, one individual was HIV-1 seropositive and one was HIV-1 seronegative. In 62% of couples, the uninfected partner was male. Seropositive participants were ineligible under national guidelines for antiretroviral therapy at the time of enrolment.

Couples received HIV-1 treatment and prevention services, including counseling and condoms.

Seronegative participants were randomized to receive once-daily tenofovir, combination emtricitabine/tenofovir, or placebo, and were followed for up to 3 years.

Jared Baeten, MD, PhD, associate professor of global health and assistant professor of allergy and infectious diseases at the University of Washington, Seattle, presented the findings. He said that medication adherence was 97% based on monthly pill counts; retention rate was 96%.

During the study period, 82 new HIV-1 infections were diagnosed. Of these, 52 occurred in the placebo group, 17 in the tenofovir group (risk reduction [RR], 67%; 95% confidence interval [CI], 44% to 81%; P < .0001), and 13 in the emtricitabine/tenofovir group (RR, 75%; 95% CI, 55% to 87%; P < .0001).

Risk reduction was observed in both men and women in the 2 treatment groups, but the difference between groups was not significantly (P = .23).

There was no difference in serious medical events in the groups. There were few cases of resistance. Of 8 subjects infected at randomization, 1 developed the K65R resistance mutation and 1 developed the M184V resistance mutation. None of the subjects who acquired HVI-1 infection after randomization developed K65R or M184V mutations.

The placebo group of the study was halted in July 2011 because of demonstrated success.

The researchers saw no evidence of increased incidence of risky behavior. In fact, condom use went up in all 3 groups, Dr. Baeten reported.

These findings are in contrast with other research presented at the meeting, which showed that a once-daily oral emtricitabine/tenofovir combination did not reduce the risk for HIV infection in 2120 women in South Africa, Kenya, and Tanzania.

The women were followed for 52 weeks, during which there were 33 new infections in the emtricitabine/tenofovir group (incidence rate, 4.7/100 person-years) and 35 in the placebo group (5.0/100 person-years; hazard ratio, 0.94; 95% CI, 0.59 to 152; P = .81).

The researchers noted that adherence was inadequate, according to pill counts and serum analysis of drug levels (detected in less than 50% of infected patients and uninfected control subjects).

The results of the couples study are encouraging, especially in light of the protective effect on women, said Chris Beyrer, MD, MPH, professor of epidemiology and international health at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, and the North American representative for the International AIDS Society.

The protective effect of treatment on men is fairly consistent. However, "there have been other studies in women where the outcome was not efficacious. This is one of the few trials of [preexposure prophylaxis] in women that showed efficacy.... That's encouraging," Dr. Beyrer told Medscape Medical News.

The difference between the 2 trials presented might be attributable to adherence to the protocol, which "is a huge challenge. People think of [pre-exposure prophylaxis] as a biomedical prevention, but it turns out it's a lot like condoms. It works great if you use it," said Dr. Beyrer.

Dr. Baeten and Dr. Beyrer have disclosed no relevant financial relationships.

19th Conference on Retroviruses and Opportunistic Infections (CROI): Abstracts 29 and 32LB. Presented March 6, 2012.

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