Higher colorectal tissue HIV infectivity in cisgender women compared with MSM before and during oral preexposure prophylaxis.

摘要: OBJECTIVE The objective of this study was to compare HIV-negative cisgender women (CGW) with MSM for mucosal tissue differences in pharmacokinetics, HIV infectivity and cell phenotype. DESIGN A substudy HPTN 069/ACTG A5305, 48-week three oral candidate preexposure prophylaxis regimens: maraviroc, maraviroc/emtricitabine maraviroc/tenofovir disoproxil fumarate (TDF) compared a TDF/emtricitabine control group. METHODS Plasma, peripheral blood mononuclear cells cervical colorectal biopsies were collected at Baseline (no drug), Week 24 48 (on 49 (1-week postdrug). Drug concentrations assessed all matrices. using biopsy 'explants' challenged ex vivo followed by p24 measurement. Flow cytometry evaluated RESULTS Thirty-seven CGW 54 participated. CGW's explant higher than before (0.31 log10, P = 0.046), during (1.01-1.19 P = 0.016) one week after (0.61 P = 0.011) drug dosing. Pooling regimens, did not differ among visits. had plasma maraviroc tenofovir diphosphate lower emtricitabine (all P < 0.005) MSM. Each drug's more 10-fold below paired (P < 0.001). Cell phenotype sex included 4% CD38+/CD8+ baseline 3-7% CD69+/CD8+ throughout Weeks 24-49 (P < 0.05). CONCLUSION Colorectal explants demonstrated greater without drugs. Small adherence, concentration flow cannot fully explain difference.