Design of epidemiological studies measuring genital and plasma HIV-1 outcomes: lessons from a randomised controlled trial.
Objective: HIV-1 genital viral loads have not been extensively used as markers of HIV transmissibility. We set out to determine whether the variability of genital HIV-1 RNA over time necessitates design adjustments in studies measuring genital shedding to account for this variability. Methods: We used data from a completed (and previously reported) trial of HSV suppressive therapy in Burkina Faso to estimate the correlation of plasma and genital HIV-1 RNA quantities sampled at different times. These correlation estimates were used to estimate the relative sample sizes needed to detect an impact on HIV-1 genital and plasma quantities assuming a variable number of pre- and post-randomisation repeated measurements. The effect of therapy on quantities of genital and plasma HIV-1 RNA was analysed using random effects linear regression. Results: Post-randomisation plasma HIV-1 RNA was highly correlated within-women (i.e. it did not very much in any given individual), while genital HIV-1 RNA was less strongly correlated. Related to this, the sample size required to detect a treatment effect on genital HIV-1 RNA decreased with increasing numbers of post-randomisation measurements up to 6–7 measurements, but varied less for plasma HIV-1 RNA. In contrast, repeated pre-randomisation measurements of plasma HIV-1 RNA increased study power more than genital HIV-1 RNA because of the high correlation of plasma HIV-1 RNA measurements between the pre- and post-randomisation samples. Re-analysis of the trial data illustrated the increased precision of the treatment effect on genital HIV-1 with increasing post-randomisation measurements. Conclusions: Designs allowing for repeated post-randomisation measures should be used to increase the precision in estimates of genital HIV-1 RNA. Repeated post-randomisation measurements of plasma HIV-1 RNA are of limited benefit. [Abstracts provided in French and Spanish].
Larke, N.L.; Weiss, H.A.; Mayaud, P.; van de Perre, P.; Clayton, T.; Ouedraogo, A.; Nagot, N. Design of epidemiological studies measuring genital and plasma HIV-1 outcomes: lessons from a randomised controlled trial. Tropical Medicine and International Health (2009) 14 (3) 267-275. [DOI: 10.1111/j.1365-3156.2009.02219.x]