Pyrimethamine and VPA do not synergize to induce HIV-1 transcription in vivo
Because of the treatment adjustments that occurred in the combination treatment arm, we used the measurements at 6 hours after the first dose to test the hypothesis that synergy occurred between pyrimethamine and VPA in the context of their combined latency reversal activity on HIV-1. In PLWH exposed to the combinatorial treatment, five of six PLWH had increased CA US HIV-1 RNA 6 hours after the first dose (In the four PLWH (LUNA-07, LUNA-12, LUNA-19, and LUNA-25) in the combination arm who continued uninterrupted pyrimethamine exposure throughout the study, the median fold change in CA US HIV-1 RNA was 1.2 (IQR, 0.9 to 2.1) at day 14. This effect was comparable to the changes observed when evaluating all PLWH including those who stopped combinatorial treatment (median, 1.4; IQR, 0.9 to 2.7). Unfortunately, the CD4