title: Permissive and protective factors associated with presence, level, and longitudinal pattern of cervicovaginal HIV shedding.
abstract: BACKGROUND
  Cervicovaginal HIV level (CV-VL) influences HIV transmission. Plasma viral load (PVL) correlates with CV-VL, but discordance is frequent. We evaluated how PVL, behavioral, immunological, and local factors/conditions individually and collectively correlate with CV-VL.
  
  
  METHODS
  CV-VL was measured in the cervicovaginal lavage fluid (CVL) of 481 HIV-infected women over 976 person-visits in a longitudinal cohort study. We correlated identified factors with CV-VL at individual person-visits and detectable/undetectable PVL strata by univariate and multivariate linear regression and with shedding pattern (never, intermittent, persistent ≥3 shedding visits) in 136 women with ≥3 visits by ordinal logistic regression.
  
  
  RESULTS
  Of 959 person-visits, 450 (46.9%) with available PVL were discordant, 435 (45.3%) had detectable PVL with undetectable CV-VL, and 15 (1.6%) had undetectable PVL with detectable CV-VL. Lower CV-VL correlated with highly active antiretroviral therapy (HAART) usage (P = 0.01). Higher CV-VL correlated with higher PVL (P < 0.001), inflammation-associated cellular changes (P = 0.03), cervical ectopy (P = 0.009), exudate (P = 0.005), and trichomoniasis (P = 0.03). In multivariate analysis of the PVL-detectable stratum, increased CV-VL correlated with the same factors and friability (P = 0.05), while with undetectable PVL, decreased CV-VL correlated with HAART use (P = 0.04). In longitudinal analysis, never (40.4%) and intermittent (44.9%) shedding were most frequent. Higher frequency shedders were more likely to have higher initial PVL [odds ratio (OR) = 2.47/log10 increase], herpes simplex virus type 2 seropositivity (OR = 3.21), and alcohol use (OR = 2.20).
  
  
  CONCLUSIONS
  Although PVL correlates strongly with CV-VL, discordance is frequent. When PVL is detectable, cervicovaginal inflammatory conditions correlate with increased shedding. However, genital shedding is sporadic and not reliably predicted by associated factors. HAART, by reducing PVL, is the most reliable means of reducing cervicovaginal shedding.
authors.affiliation: Maternal, Child and Adolescent Center for Infectious Diseases and Virology, Department of Pediatrics, Division of Infectious Disease, University of Southern California Keck School of Medicine, Los Angeles, CA. USA. homans@usc.edu
authors.forename: James
authors.initials: J
authors.lastname: Homans
authors.forename: Shawna
authors.initials: S
authors.lastname: Christensen
authors.forename: Tracey
authors.initials: T
authors.lastname: Stiller
authors.forename: Chia-Hao
authors.initials: CH
authors.lastname: Wang
authors.forename: Wendy
authors.initials: W
authors.lastname: Mack
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.forename: Mary
authors.initials: M
authors.lastname: Young
authors.forename: Ruth
authors.initials: R
authors.lastname: Greenblatt
authors.forename: Mardge
authors.initials: M
authors.lastname: Cohen
authors.forename: Howard
authors.initials: H
authors.lastname: Strickler
authors.forename: Roksana
authors.initials: R
authors.lastname: Karim
authors.forename: Lashonda Yvette
authors.initials: LY
authors.lastname: Spencer
authors.forename: Eva
authors.initials: E
authors.lastname: Operskalski
authors.forename: Toinette
authors.initials: T
authors.lastname: Frederick
authors.forename: Andrea
authors.initials: A
authors.lastname: Kovacs
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage; D023241:Antiretroviral Therapy, Highly Active; D002584:Cervix Uteri / Q000821:virology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D011446:Prospective Studies; D014621:Vagina / Q000821:virology*; D019562:Viral Load; D017201:Virus Shedding
chemical_list: D019380:Anti-HIV Agents