A Phase 1 Clinical Trial to Assess the Safety and Pharmacokinetics of a Tenofovir Alafenamide/Elvitegravir Insert Administered Rectally for HIV Prevention

J Infect Dis. 2024 Sep 23;230(3):696-705. doi: 10.1093/infdis/jiae211.

Abstract

Background: On-demand topical products could be an important tool for human immunodeficiency virus (HIV) prevention. We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide/elvitegravir (TAF/EVG, 20 mg/16 mg) insert administered rectally.

Methods: MTN-039 was a phase 1, open-label, single-arm, 2-dose study. Blood, rectal fluid, and rectal tissue were collected over 72 hours following rectal administration of 1 and 2 TAF/EVG inserts for each participant.

Results: TAF/EVG inserts were safe and well tolerated. EVG and tenofovir (TFV) were detected in blood plasma at low concentrations: median peak concentrations after 2 inserts were EVG 2.4 ng/mL and TFV 4.4 ng/mL. Rectal tissue EVG peaked at 2 hours (median, 2 inserts = 9 ng/mg) but declined to below limit of quantification in the majority of samples at 24 hours, whereas tenofovir diphosphate (TFV-DP) remained high >2000 fmol/million cells for 72 hours with 2 inserts. Compared to baseline, median cumulative log10 HIV p24 antigen of ex vivo rectal tissue HIV infection was reduced at each time point for both 1 and 2 inserts (P < .065 and P < .039, respectively).

Discussion: Rectal administration of TAF/EVG inserts achieved high rectal tissue concentrations of EVG and TFV-DP with low systemic drug exposure and demonstrable ex vivo inhibition of HIV infection for 72 hours. Clinical Trials Registration . NCT04047420.

Keywords: HIV prevention; elvitegravir; microbicide; rectal insert; tenofovir alafenamide.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adenine* / administration & dosage
  • Adenine* / adverse effects
  • Adenine* / analogs & derivatives
  • Adenine* / pharmacokinetics
  • Administration, Rectal*
  • Adult
  • Alanine* / administration & dosage
  • Alanine* / pharmacokinetics
  • Anti-HIV Agents* / administration & dosage
  • Anti-HIV Agents* / adverse effects
  • Anti-HIV Agents* / pharmacokinetics
  • Drug Combinations
  • Female
  • HIV Infections* / drug therapy
  • HIV Infections* / prevention & control
  • HIV-1 / drug effects
  • Humans
  • Male
  • Middle Aged
  • Quinolones* / administration & dosage
  • Quinolones* / adverse effects
  • Quinolones* / pharmacokinetics
  • Rectum / virology
  • Tenofovir* / administration & dosage
  • Tenofovir* / analogs & derivatives
  • Tenofovir* / pharmacokinetics
  • Young Adult

Substances

  • Tenofovir
  • elvitegravir
  • Quinolones
  • tenofovir alafenamide
  • Anti-HIV Agents
  • Alanine
  • Adenine
  • Drug Combinations

Associated data

  • ClinicalTrials.gov/NCT04047420