Persisting with prevention: The importance of adherence for HIV prevention

We 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 behavior and the binomial model for the transmission probability per partnership.At 100% adherence the measured efficacy within an RCT 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.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 RCTs and HIV prevention programmes.Recent randomized controlled trials (RCT) of herpes suppressive therapy [1,2], female diaphragms and gel in addition to male condoms (the Methods for Improving Reproductive Health in Africa, or MIRA trial) [3], and an adenovirus-vectored HIV vaccine [4] have failed to show an impact on HIV acquisition. These disappointing findings contribute to a total of 31 completed RCTs with HIV incidence as a primary outcome for sexual transmission (Table 1), of which only four have shown a statistically significant reduction in new HIV infections [5-8].Multiple factors are likely to be responsible for the failure of the trials to see a protective effect, including interventions which are truly non-efficacious, trials which were under-powered to detect an effect, and poor adherence to the intervention under study. It is striking that the only intervention for which multiple trials have shown efficacy in preventing HIV is male circumcision [5-7], a non-reversible surgical procedure for which