title: Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding.
abstract: BACKGROUND
  Antiretroviral therapy (ART) may decrease HIV-1 infectivity in women by reducing genital HIV-1 shedding.
  
  
  OBJECTIVE
  To evaluate the time course and magnitude of decay in cervical and vaginal HIV-1 shedding as women initiate ART.
  
  
  METHODS
  This prospective, observational study of 20 antiretroviral-naive women initiating ART with stavudine, lamivudine, and nevirapine measured HIV-1 RNA in plasma, cervical secretions, and vaginal secretions. Qualitative polymerase chain reaction estimated HIV-1 DNA in cervical and vaginal samples. Perelson's two-phase viral decay model and non-linear random effects were used to compare RNA decay rates. Decreases in proviral DNA were evaluated using logistic regression and generalized estimating equations.
  
  
  RESULTS
  Significant decreases in the quantity of HIV-1 RNA were observed by day 2 in plasma (P < 0.001), day 2 in cervical secretions (P = 0.001), and day 4 in vaginal secretions (P < 0.001). Modeled initial and subsequent RNA decay rates in plasma, cervical secretions, and vaginal secretions were 0.6, 0.8, and 1.2 log10 virions/day, and 0.04, 0.05, and 0.06 log10 virions/day, respectively. The initial decay rate for vaginal HIV-1 RNA was more rapid than for plasma RNA (P = 0.02). Detection of HIV-1 DNA decreased significantly in vaginal secretions during the first week (P < 0.001). At day 28, 10 women had detectable HIV-1 RNA or proviral DNA in genital secretions.
  
  
  CONCLUSIONS
  Genital HIV-1 shedding decreased rapidly after ART initiation, consistent with a rapid decrease in infectivity. However, incomplete viral suppression in half of these women may indicate an ongoing risk of transmission.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA. grahamsm@u.washington.edu
authors.forename: Susan M
authors.initials: SM
authors.lastname: Graham
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Holte
authors.forename: Norbert M
authors.initials: NM
authors.lastname: Peshu
authors.forename: Barbra A
authors.initials: BA
authors.lastname: Richardson
authors.forename: Dana D
authors.initials: DD
authors.lastname: Panteleeff
authors.forename: Walter G
authors.initials: WG
authors.lastname: Jaoko
authors.forename: Jeckoniah O
authors.initials: JO
authors.lastname: Ndinya-Achola
authors.forename: Kishorchandra N
authors.initials: KN
authors.lastname: Mandaliya
authors.forename: Julie M
authors.initials: JM
authors.lastname: Overbaugh
authors.forename: R Scott
authors.initials: RS
authors.lastname: McClelland
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002584:Cervix Uteri / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D011446:Prospective Studies; D011533:Proviruses / Q000302:isolation & purification; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D011477:Sex Work; D016896:Treatment Outcome; D014621:Vagina / Q000821:virology*
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral