Background:  Providing or facilitating access to an optimal standard of care for trial participants is a critical responsibility for clinical investigators. For male participants in HIV prevention trials, this includes circumcision, which is highly effective in reducing the risk of HIV acquisition. We describe our experience in introducing circumcision as a component of the standard of care in an HIV vaccine efficacy trial.

Methods:  We examined data from male participants in a phase IIb HIV vaccine trial, HVTN 503 (Phambili Trial), enrolled at the Soweto, South Africa site between study initiation (January 2007) and August 31, 2007. The study site counseled men on potential benefits and provided circumcision to men choosing to become circumcised. Participants were categorized as circumcised at baseline, uncircumcised at baseline and during follow-up, or circumcised during follow-up. We examined the relationship between these categories and demographic characteristics, self-reported risk behaviors, and reasons for trial participation.

Results:  We enrolled and followed for a mean of 99 days, 158 HIV-uninfected men, mean age 22.5 years. Of these, 45 (28.5%) were circumcised at baseline (mean, 9.4 years prior to enrolment); 20 men (17.6%) chose to be circumcised after joining the trial. The procedure was done between 15 and 120 days after enrolment (median, 71 days). Men circumcised at baseline or circumcised during follow-up were slightly older than men who remained uncircumcised (23.6 vs 21.8 years, p = 0.0055). Of all men, 87% agreed that one of the reasons for joining the trial was tests or medical care provided; this response was similar across circumcision status groups (p = 0.865). At enrolment, men circumcised during follow-up reported slightly more female sexual partners in the past 6 months than men circumcised at baseline or uncircumcised (mean, 3.2 vs 2.2 vs 2.3, p = 0.138), and 15% of men circumcised during follow-up reported a known HIV-infected partner in the prior 6 months vs 2% of men circumcised at baseline and no uncircumcised men, (p = 0.0005). Men circumcised during follow-up were also more likely to have reported diagnosis of a sexually transmitted disease within the prior 6 months (20% vs 15.6% circumcised at baseline vs 3.2% uncircumcised, p = 0.005) and a slightly higher number of binge drinking episodes in the 6 months before enrolment (circumcised during follow-up 10.5 vs circumcised at baseline 9.1 vs uncircumcised 7.8, p = 0.68).

Conclusions:  A large proportion of young men enrolled in the trial accepted male circumcision soon after study entry. Uptake of this magnitude has implications for sample size in HIV prevention trials. Men circumcised during follow-up may have lifestyle factors that place them at higher risk of acquiring HIV than other men entering the trial.