Statistical analysis
The sample size was based on the null hypothesis that the change in CA US HIV-1 RNA between the study arms is equal and the alternative hypothesis that the change in CA US HIV-1 RNA is not equal. Assuming a mean change of 31 copies of CA US HIV-1 RNA (SD estimated at 20) by the intervention based on previous trials (The measurements related to the end points CA US HIV-1 RNA, MS HIV-1 RNA, plasma HIV-1 RNA, and drug plasma levels were described as median with IQR or full range. When the CA US HIV-1 RNA measurement was below the limit of quantitation set at 16 copies per 150 ng of total RNA, we imputed 16 copies at these data points for further calculations. The fold change difference per study arm from pretreatment CA US HIV-1 RNA levels to the time points 6 hours, day 14, and day 42 after first dosing was calculated by adding up the fold change per individual divided by the total number of measurements available per time point. We analyzed the primary end point by a generalized estimating equation model to evaluate whether any difference in the CA US HIV-1 RNA existed at any time point during the trial in any of the three interventional arms compared to the control arm. An interaction term of time and treatment was included. We used the Bliss independence method to conclude on synergism between pyrimethamine and VPA using the following equation μ