Simultaneous plasma and genital pharmacokinetics and pharmacodynamics of atazanavir and efavirenz in HIV-infected women starting therapy

J Clin Pharmacol. 2015 Jul;55(7):798-808. doi: 10.1002/jcph.481. Epub 2015 Mar 30.

Abstract

Few studies have characterized longitudinal female plasma and genital antiretroviral pharmacokinetics and pharmacodynamics. Among 20 regimen-naive HIV-infected adult women initiating atazanavir-based therapy (n = 9) or efavirenz-based therapy (n = 11), we measured blood CD4+ T lymphocytes, and paired plasma and genital HIV RNA and atazanavir or efavirenz 2 days before starting therapy and 2, 4, 7, 10, 21, 28, 60, 120, and 180 days after. The mean (range) log10 baseline plasma viral load was 4.89 copies/mL (2.64-6.09 copies/mL), and genital was3.30 (1.60-5.00). In the atazanavir and efavirenz groups, mean (SD) days to a 50% decrease in plasma viral load was 8.2 (4.9) versus 9.3 (7.4), P = .7, and in the genital tract it was 7.3 (3.5) versus 9.3 (7.7), P = .5. The median (interquartile range) plasma:genital concentration ratio for atazanavir was 0.11 (0.001-0.46) versus 0.34 (0.05-1.30) for efavirenz, P = .5. Average plasma efavirenz or atazanavir concentrations over time did not affect virologic response. Blood CD4+ percentages increased by +2.3 (P = .06) and +3.0 (P = .003) for every 1 mg/L increase in average plasma and genital drug concentration, respectively. Plasma and genital viral pharmacodynamics were similar between the groups and independent of average concentrations, but blood CD4+ response was related in particular to genital extravascular drug concentrations.

Keywords: HIV; female; genital; pharmacodynamics; pharmacokinetics.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alkynes
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / pharmacology
  • Atazanavir Sulfate / administration & dosage*
  • Atazanavir Sulfate / pharmacokinetics
  • Atazanavir Sulfate / pharmacology
  • Benzoxazines / administration & dosage*
  • Benzoxazines / pharmacokinetics
  • Benzoxazines / pharmacology
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Middle Aged
  • RNA, Viral / blood
  • Viral Load / drug effects
  • Young Adult

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • RNA, Viral
  • Atazanavir Sulfate
  • efavirenz