Genital secretion HIV RNA shedding in HIV-positive patients on ritonavir-boosted protease inhibitor monotherapy or standard combination ART: a cross-sectional sub-study from the PIVOT Trial.

BACKGROUND: Protease inhibitors (PI) have relatively low penetration into the genital tract, raising concerns about the potential for genital HIV-RNA shedding in patients taking PI-based regimens, particularly PI monotherapy (PImono). METHODS: We measured HIV-RNA and PI drug concentrations in samples of semen; cervico-vaginal and rectal mucosa secretions; and plasma in patients after 48-96 weeks on PImono or standard triple therapy. RESULTS: A total of 85 participants were recruited. Of the 43 participants on PImono (70% on Darunavir (DRV)/ritonavir (r)), 3 had detectable virus in semen or vaginal secretions (all below quantification limit), and none in rectal mucosa or plasma. Among those taking triple therapy, 5 had detectable virus in semen or vaginal secretions (HIV-RNA >50 copies/ml in one), none in rectal mucosa, and one in plasma. The median (IQR) concentration of darunavir and atazanavir in semen (659.7 (339 - 1089) and 128.8 (63 - 368) ng/mL respectively) and cervico-vaginal samples (2768 (312 - 7879) and 1836 (359 - 3314) ng/mL respectively) exceeded their protein adjusted median inhibition concentration (MIC50). Darunavir (DRV) concentration in rectal secretions showed higher variability compared to concentration in the other sites, with particularly high rectal secretion/blood ratios (median 8.4; IQR 2.6 - 68.7:1). CONCLUSIONS: We found no substantive evidence of HIV shedding in patients taking PI monotherapy, suggesting that protease inhibitors provide adequate control of virus in the genital compartment and are unlikely to lead to ongoing sexual transmission.