tenofovir intravaginal ring (GS 1278) / Gilead, CONRAD - LARVOL DELTA

Phase 1 randomized pharmacokinetic and safety study of a 90-day tenofovir vaginal ring in the United States. (PubMed, J Int AIDS Soc) - "The 90-day TFV ring was well-tolerated, acceptable and exceeded target cervical tissue concentrations through day 56, but declined thereafter. Additional studies are needed to characterize the higher release from TFV rings in some participants and the optimal duration of use."

Journal • P1 data • PK/PD data • Herpes Simplex • Human Immunodeficiency Virus • Infectious Disease

Randomized controlled phase IIa clinical trial of safety, pharmacokinetics and pharmacodynamics of tenofovir and tenofovir plus levonorgestrel releasing intravaginal rings used by women in Kenya. (PubMed, Front Reprod Health) - P2a | "We further evaluated TFV pharmacodynamics (PD) through ex vivo CVF activity against both human immunodeficiency virus (HIV)-1 and herpes simplex virus (HSV)-2, and LNG PD using cervical mucus quality markers and serum progesterone for ovulation inhibition...Steady state geometric mean amount (ssGMA) of vaginal TFV was comparable in the TFV/LNG and TFV IVR groups, 43,988 ng/swab (95% CI, 31,232, 61,954) and 30337 ng/swab (95% CI, 18,152, 50,702), respectively...Pharmacokinetics and markers of protection against HIV-1, HSV-2, and unintended pregnancy suggest the potential for clinical efficacy of the multipurpose TFV/LNG IVR. NCT03762382 [https://clinicaltrials.gov/ct2/show/NCT03762382]."

Journal • P2a data • PK/PD data • Hepatitis B • Hepatology • Herpes Simplex • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Vaginitis

PHASE I PK, SAFETY, AND ACCEPTABILITY STUDY OF A 90-DAY TENOFOVIR VAGINAL RING (CROI 2022) - "The 90-day TFV ring was well-tolerated, acceptable, and exceeded target cervical tissue concentrations through day 56, but declined thereafter. Additional studies should characterize the higher release from TFV rings in some participants and the optimal duration of use."

Clinical • P1 data • Human Immunodeficiency Virus • Infectious Disease

Genital Mucosal Drug Concentrations and anti-HIV Activity in Tenofovir-Based PrEP Products: Intravaginal Ring vs. Oral Administration. (PubMed, J Acquir Immune Defic Syndr) - "Both products were safe and increased mucosal HIV inhibitory activity. In addition to systemic protection, oral TDF/FTC displays a PK/PD profile compatible with CV mucosal antiviral activity. TFV IVR resulted in fewer AEs, lower TFV plasma concentrations, higher CVF and tissue TFV and TFV-DP concentrations, and greater anti-HIV activity in CVF."

Journal • Human Immunodeficiency Virus • Infectious Disease

[VIRTUAL] Tenofovir-only and tenofovir/levonorgestrel intravaginal rings are unlikely to impact the genital microbiota of sub-Saharan women (HIVR4P 2021) - "Compared to the genital lateral wall, the TFV/LNG IVR tended to have a higher biomass, the placebo IVR a lower biomass, and no difference with the TFV IVR... We found that the TFV and TFV/LNG IVRs had no sign of detrimental impact on genital microbiota, with the latter being associated with increased lactobacillus abundance. These findings warrant further investigation in next-phase studies of these IVR."

Clinical • Human Immunodeficiency Virus • Infectious Disease

[VIRTUAL] Dose response to tenofovir disoproxil fumarate and tenofovir released via intravaginal ring in the sheep vaginal safety and pharmacokinetics model (HIVR4P 2021) - "Similarly, seven of eight sheep had mucosal disruption while using the 10-pod TFV IVR. The sheep model for safety and PK assessment of vaginal TDF delivery closely approximated findings from a clinical trial using the same TDF IVR. Vaginal toxicity was noted with higher doses of TDF and TFV, regardless of type of IVR used for drug delivery. Results demonstrate that the sheep model provides opportunities for exploration of mechanisms of drug toxicity and rapid iterative drug development."

Clinical • Late-breaking abstract • PK/PD data • Immunology • Inflammation • CXCL8

Tenofovir/Levonorgestrel Intravaginal Ring and Tenofovir Intravaginal Ring (clinicaltrials.gov) - P2a; N=50; Active, not recruiting; Sponsor: CONRAD; Trial completion date: Aug 2019 ➔ Apr 2020

Clinical • Trial completion date • CXCL8