Etravirine concentrations in seminal plasma in HIV-infected patients

J Antimicrob Chemother. 2013 Jan;68(1):184-7. doi: 10.1093/jac/dks360. Epub 2012 Sep 6.

Abstract

Objectives: To determine etravirine concentrations and the HIV-1 viral load (VL) in blood plasma (BP) and seminal plasma (SP) of HIV-infected patients.

Methods: Ten adult antiretroviral-experienced HIV-1 patients receiving an etravirine-containing regimen for at least 1 month were enrolled. Semen and blood samples were collected ~12 or 24 h after the last etravirine dose, depending on twice-daily or once-daily dosing, respectively. Liquid chromatography tandem mass spectrometry was used to determine etravirine concentrations and HIV-1 VL was determined by real-time PCR (detection limit 40 copies/mL). Results are presented as the median (range) unless otherwise indicated.

Results: Ten blood and 20 semen samples were collected. The CD4 count was 502 (252-817) cells/mm(3) and the BP VL was <40 (<40-362) copies/mL. The time on etravirine was 52 (12-124) weeks. The BP etravirine concentration was 452.5 (258-751) ng/mL. The SP etravirine concentration was 62.9 (31.2-166.0) ng/mL and values were above the IC(50) range (0.39-2.4 ng/mL) in all cases. The median etravirine SP:BP ratio was 0.16 (0.07-0.26). The SP VL was <40 copies/mL in all patients, whereas the BP VL was detectable in one patient with poor adherence to treatment.

Conclusions: Etravirine concentrations in male genital secretions are modest, reaching only 16% of the BP concentration. Nevertheless, they are more than 10 times greater than the wild-type IC(50) range (not adjusted for protein binding).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / metabolism
  • Anti-HIV Agents / therapeutic use
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / metabolism*
  • HIV-1 / drug effects*
  • HIV-1 / metabolism
  • Humans
  • Male
  • Middle Aged
  • Nitriles
  • Pyridazines / blood
  • Pyridazines / metabolism*
  • Pyridazines / therapeutic use*
  • Pyrimidines
  • Semen / drug effects*
  • Semen / metabolism*
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Nitriles
  • Pyridazines
  • Pyrimidines
  • etravirine