title: HIV-1 genital shedding is suppressed in the setting of high genital antiretroviral drug concentrations throughout the menstrual cycle.
abstract: BACKGROUND
  It is not known if fluctuations in genital tract antiretroviral drug concentrations correlate with genital virus shedding in human immunodeficiency virus (HIV)-infected women on antiretroviral therapy (ART).
  
  
  METHODS
  Among 20 HIV-infected women on ART (tenofovir [TFV], emtricitabine [FTC], and ritonavir-boosted atazanavir [ATV]) with suppressed plasma virus loads, blood and cervicovaginal samples collected twice weekly for 3 weeks were tested for antiretroviral concentrations, HIV-1 RNA, and proviral DNA.
  
  
  RESULTS
  Cervicovaginal:plasma antiretroviral concentration ratios were highest for FTC (11.9, 95% confidence interval [CI], 8.66-16.3), then TFV (3.52, 95% CI, 2.27-5.48), and ATV (2.39, 95% CI, 1.69-3.38). Within- and between-person variations in plasma and genital antiretroviral concentrations were observed. Low amounts of genital HIV-1 RNA (<50 copies/mL) were detected in 45% of women at 16% of visits. Genital HIV-1 DNA was detected in 70% of women at 35% of visits. Genital virus detection was associated with higher concentrations of mucosal leukocytes but not with genital antiretroviral concentrations, menstrual cycle phase, bacterial vaginosis, genital bleeding, or plasma virus detection.
  
  
  CONCLUSIONS
  Standard doses of ART achieved higher genital than plasma concentrations across the menstrual cycle. Therapeutic ART suppresses genital virus shedding throughout the menstrual cycle, even in the presence of factors reported to increase virus shedding.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine.
authors.forename: Anandi N
authors.initials: AN
authors.lastname: Sheth
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention.
authors.forename: Tammy
authors.initials: T
authors.lastname: Evans-Strickfaden
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention.
authors.forename: Richard
authors.initials: R
authors.lastname: Haaland
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention.
authors.forename: Amy
authors.initials: A
authors.lastname: Martin
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Gatcliffe
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention.
authors.forename: Adebola
authors.initials: A
authors.lastname: Adesoye
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Omondi
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention.
authors.forename: L Davis
authors.initials: LD
authors.lastname: Lupo
authors.affiliation: Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Damien
authors.initials: D
authors.lastname: Danavall
authors.affiliation: Department Biostatistics and Bioinformatics, Emory University School of Public Health.
authors.forename: Kirk
authors.initials: K
authors.lastname: Easley
authors.affiliation: Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Cheng-Yen
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention.
authors.forename: Chou-Pong
authors.initials: CP
authors.lastname: Pau
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention.
authors.forename: Clyde
authors.initials: C
authors.lastname: Hart
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine.
authors.forename: Igho
authors.initials: I
authors.lastname: Ofotokun
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000068679:Emtricitabine; D005260:Female; D005836:Genitalia, Female / Q000737:chemistry* / Q000821:virology*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008597:Menstrual Cycle; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics; D010949:Plasma / Q000737:chemistry / Q000821:virology; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068698:Tenofovir; D019562:Viral Load; D017201:Virus Shedding
chemical_list: D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D012367:RNA, Viral; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir
keywords: HIV-1; female genital tract; pharmacology; viral shedding