Two major studies show that HIV drugs prevent infection

Two large studies of pre-exposure prophylaxis – use of antiretroviral drugs by uninfected people to prevent HIV infection – have shown that taking tenofovir or tenofovir plus emtricitabine (Truvada) can cut the risk of HIV infection through sexual transmission by between 62% and 78% in male-female couples. Results from both the Partners study and the TDF2 study were released today.

“This study demonstrates that antiretrovirals are a highly potent and fundamental cornerstone for HIV prevention and should become an integral part of global efforts for HIV prevention,” said Dr Connie Celum, Professor of Global Health and Medicine at the University of Washington, Seattle.

The results, released this morning ahead of the International AIDS Society (IAS) conference in Rome next week, follow positive results from the IPrEX study of Truvada PrEP in men who have sex with men released in November 2010.

Fuller results from the studies will be presented next week.

The Partners study took place in Kenya and Uganda. It recruited 4,758 male-female couples in which one partner was HIV-positive. The uninfected partners were randomised to receive either tenofovir, tenofovir plus emtricitabine (Truvada) or a placebo. The medication was taken daily, and all participants received counselling on safer sex, both individually and as a couple, and received free condoms and monitoring and treatment for sexually transmitted infections.

The study was halted more than 18 months early after an interim review of the data found a highly significant effect of PrEP.

The risk of infection was reduced by 62% in those who received tenofovir alone (95% confidence interval 34% - 78%, p=0.0003), and by 73% in those who received Truvada (95% CI 49% - 85%; p<0.0001). The difference in protection was not signficantly different between the two PrEP regimens, nor was there any significant difference in protection between men and women.

Seventy-eight infections were recorded: 18 in the tenofovir group, 13 in the Truvada group, and 47 in the placebo group.

Adherence was very high; more than 97% of doses dispensed were taken, and 95% of participants stayed in the study.

The investigators say that rates of serious adverse events were similar across the three study arms.

“This is an extremely exciting finding for the field of HIV prevention. Now, more than ever, the priority for HIV prevention research must be on how to deliver successful prevention strategies, like PrEP, to populations in greatest need,” said Dr. Jared Baeten, co-chair of the study and a UW associate professor of global health and medicine.

The Partners study was funded by the Bill and Melinda Gates Foundation.

In the TDF2 study, conducted in Botswana, 1,200 men and women (55% men) were enrolled and randomised to receive either Truvada or placebo. Overall, Truvada reduced the risk of infection by 63%.

In this primary analysis there were nine HIV infections amongst the 601 participants who received Truvada and 24 among the 599 who received placebo. This translates into a statistically significant 62.6% reduction in infections.

A secondary analysis, however, excluded infections that occurred amongst people who had run out of their Truvada/placebo pills and who had not taken one for at least 30 days. This found 77.9% fewer infections in people taking Truvada.

Full results analysing efficacy by gender and other characteristics will be announced at the IAS Conference.

The TDF2 study was run by the US Centers for Disease Control in partnership with the Botswana Ministry of Health.

The results of the two studies stand in contrast to the decision to halt the FEM PrEP trial, after researchers concluded that the study would not be able to show that Truvada PrEP was effective in preventing HIV infection in women in South Africa, Kenya and Tanzania, even if it went on to its planned conclusion.

In that study adherence was lower, although the precise levels of adherence have still to be presented. The FEM PrEP study also found a higher rate of pregnancies in the Truvada recipients, a result that was not replicated in the Partners study.

The IPrEX study showed that use of Truvada reduced the risk of HIV infection by 44%, but reduced the risk of infection among men who took it more than 90% of the time by 73%.