Penetration and antiviral efficacy of total and unbound maraviroc, raltegravir and rilpivirine in both female and male genital fluids from HIV-positive patients receiving regimens containing these antiretrovirals

Abstract

Background: Sub-optimal penetration of antiretroviral drugs in genital compartments might promote local HIV persistence and increase the risk of HIV transmission. Objectives: To describe the penetration of maraviroc, raltegravir, raltegravir glucuronide and rilpivirine in seminal plasma and cervico-vaginal secretions (CVS) and to assess local antiretroviral efficacy in HIV-1-positive patients. Methods: This was a prospective, multicentre study. Inclusion criteria were HIV-1 positive, age > 18 years, receiving regimens containing maraviroc and/or raltegravir and/or rilpivirine for > 1month, and good self-reported adherence. Paired blood and genital samples were collected 12 h (raltegravir and maraviroc) or 24 h (rilpivirine) post-dose. These concentrations were determined (UPLC-MS/MS) in blood and seminal plasma (total and unbound) and CVS (total, dried spots) and HIV-RNA was quantified in paired blood and genital samples. Results: Among the 54 enrolled patients, 15 received maraviroc (6 men), 27 received raltegravir (14 men) and 20 received rilpivirine (10 men), corresponding to 54 total and 52 unbound plasma concentrations, 29 total CVS samples and 23 total and 18 unbound seminal plasma samples. Maraviroc and raltegravir displayed a ratio of genital fluids/plasma concentrations > 0.5 in both male and female genital tracts. Conversely, rilpivirine displayed a low ratio. Antiretroviral free fractions were consistent with historical data. Nine patients had blood plasma HIV-RNA > 50 copies/mL (2/9 had sub-optimal antiretroviral blood plasma exposure) and two other patients had detectable HIV-RNA in genital fluids. Conclusions: Maraviroc and raltegravir demonstrated good penetration in genital compartments, yielding good local virological response in genital compartments, whereas rilpivirine presented a low penetration profile but good local response.