title: Simultaneous plasma and genital pharmacokinetics and pharmacodynamics of atazanavir and efavirenz in HIV-infected women starting therapy.
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.
authors: Laboratory of Applied Pharmacokinetics, Children's Hospital Los Angeles and the Keck School of Medicine at the University of Southern California, Los Angeles, CA, USA.
authors: Michael
authors: M
authors: Neely
authors: Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics & Policy Faculty, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
authors: Stan
authors: S
authors: Louie
authors: Maternal, Child and Adolescent Center for Virology and Infectious Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Jiaao
authors: J
authors: Xu
authors: Maternal, Child and Adolescent Center for Virology and Infectious Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Patricia
authors: P
authors: Anthony
authors: Maternal, Child and Adolescent Center for Virology and Infectious Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Kasalyn
authors: K
authors: Thuvamontolrat
authors: Stanford University School of Medicine, Stanford, CA, USA.
authors: Nicholas
authors: N
authors: Mordwinkin
authors: Maternal, Child and Adolescent Center for Virology and Infectious Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Andrea
authors: A
authors: Kovacs
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000069446:Atazanavir Sulfate / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D048588:Benzoxazines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D012367:RNA, Viral; D000069446:Atazanavir Sulfate; C098320:efavirenz
keywords: HIV; female; genital; pharmacodynamics; pharmacokinetics