The Partners PrEP trial

The results of two more PrEP trials were announced in July 2011 at the International AIDS Society conference in Rome. Both showed efficacies higher than the iPrEx trial, and although there was a suggestion that in one trial, PrEP might be less efficacious in women than men, this may be due to lifestyle issues such as the ability of women to attend the clinic rather than to biological difference.

The Partners trial, which was funded by the Bill and Melinda Gates Foundation, took place in Kenya and Uganda.¹ It recruited 4758 male-female couples in which one partner was HIV positive. The HIV-negative partner was female in 38% of the couples.

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.

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

This meant that the risk of infection was reduced by 62% in those who received tenofovir alone (95% confidence interval 34 to 78%; p = 0.0003), and by 73% in those who received Truvada (95% CI 49 to 85%; p < 0.0001). This difference in protection between the two PrEP regimens was not statistically significant.

There was no difference in efficacy of either tenofovir or Truvada between men and women. The efficacy of tenofovir was 68% in women and 58% in men; the efficacy of Truvada was 62% in women and 83% in men. None of the differences between men and women were statistically significant.

Adherence was reported as excellent throughout, with approximately 97% adherence in all arms, and a strong correlation between self-reported adherence and pill count. Researchers speculated that adherence might tend to be higher in couples, especially ones who received adherence and sexual risk counselling together, as they would tend to look after each other. Although 27% of the couples reported unprotected sex in the previous month at baseline, this declined throughout the study to about 10% at month 30.

In terms of side-effects, there were 17 cases of raised creatinine (indicative of kidney malfunction) on tenofovir and 20 on Truvada compared to 12 on placebo – not a significant difference.

Twelve participants who had tested HIV negative at screening were found to have acute HIV infection. This is a reminder that one of the most problematic aspects of PrEP is the need to exclude patients who are in the process of seroconverting to HIV from taking it.