Genital Mucosal Drug Concentrations and anti-HIV Activity in Tenofovir-Based PrEP Products: Intravaginal Ring vs. Oral Administration

Objective: To describe and compare systemic and local pharmacokinetics (PK) and cervicovaginal (CV) pharmacodynamics (PD) of oral tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) with tenofovir (TFV) intravaginal ring (IVR). Design: Phase I, randomized, parallel-group study. Women (n = 22) used TDF/FTC oral tablets daily or TFV IVR continuously and were assessed at baseline and 14 days. Methods: TFV and FTC concentrations were measured in plasma, CV fluid (CVF), and CV tissue. TFV-diphosphate and FTC-triphosphate were assessed in CV tissue. In vitro PD antiviral activities of TFV and FTC (using in vivo concentration ranges) were modeled in the CVF and by infecting CV tissue explants ex vivo with HIV-1BaL. Results: Adverse events (AEs) were more common with oral TDF/FTC use (P 100-fold higher among IVR users. The median CVF FTC concentrations were 103 ng/mL. FTC and FTC-triphosphate were detected in all CV tissues from TDF/FTC users. HIV inhibitory activity of CVF increased significantly with treatment in both cohorts (P
Source: JAIDS Journal of Acquired Immune Deficiency Syndromes - Category: Infectious Diseases Tags: Clinical Science Source Type: research