HIV This Week

Weiss HA, Wasserheit JN, Barnabas RV, Hayes RJ, Abu-Raddad LJ. Persisting with prevention: The importance of adherence for HIV prevention. Emerg Themes Epidemiol. 2008 Jul 11;5:8.

Only four out of 31 completed randomised controlled trials of HIV prevention strategies against sexual transmission have shown significant efficacy. Poor adherence may have contributed to the lack of effect in some of these trials. In this paper Weiss et al explore the impact of various levels of adherence on measured efficacy within a randomized controlled trial. They used simple quantitative methods to illustrate the impact of various levels of adherence on measured efficacy by assuming a uniform population in terms of sexual behaviour and the binomial model for the transmission probability per partnership. At 100% adherence the measured efficacy within a randomised controlled trial is a reasonable approximation of the true biological efficacy. However, as adherence levels fall, the efficacy measured within a trial substantially under-estimates the true biological efficacy. For example, at 60% adherence, the measured efficacy can be less than half of the true biological efficacy. The authors conclude that poor adherence during a trial can substantially reduce the power to detect an effect, and improved methods of achieving and maintaining high adherence within trials are needed. There are currently 12 ongoing HIV prevention trials, all but one of which require ongoing user-adherence. Attention must be given to methods of maximizing adherence when piloting and designing randomised controlled trials RCTs and HIV prevention programmes.

Editors’ note: Anticipated levels of adherence to prevention measures, which are likely to be lower than those achieved with antiretroviral treatment, must be taken into account when designing trials. Trials need to be powered to detect a smaller efficacy than a true biological efficacy that would result from 100% adherence. Otherwise it is not clear whether a null result, as has been seen in several trials, reflects a truly ineffective intervention; low study power due to factors such as underestimates of HIV incidence, effective intervention in the control arm, and higher than expected loss to follow-up; or poor adherence. Methods to achieve and maintain high adherence in a trial are key to successful trial conduct but also to eventual application of any prevention method that does prove efficacious.