title: Natural history and possible reactivation of human papillomavirus in human immunodeficiency virus-positive women.
abstract: BACKGROUND
  Little is known in human immunodeficiency virus (HIV)-positive women about how the combination of plasma HIV RNA level and CD4+ T-cell count is associated with the natural history of human papillomavirus (HPV) infection or about HPV reactivation--whether it occurs and with what frequency in HIV-positive women.
  
  
  METHODS
  HIV-positive (n = 1848) and -negative (n = 514) women were assessed at semiannual visits (total person-years = 5661) for cervicovaginal HPV with polymerase chain reaction assays and for squamous intraepithelial lesions (SILs) by Pap smear. We studied the prevalent detection of HPV and SILs with generalized estimating equations and the incident detection and persistence of HPV and SILs with multivariable Cox models. All statistical tests were two-sided.
  
  
  RESULTS
  We observed a strong interaction between the associations of CD4+ and plasma HIV RNA strata with both prevalent (P(interaction) = .002) and incident (P(interaction) = .001) detection of HPV. Indeed, the hazard ratio for incident HPV detection peaked between 4.0 and 5.0, with either a CD4+ count of less than 200 cells per mm3 or an HIV RNA level of more than 100,000 copies per mL. Although incident HPV detection in all women was associated with the number of recent sex partners (P(trend)<.001), 22% of sexually inactive HIV-positive women with a CD4+ count of less than 200 cells/mm3 also had at least one incidentally detected HPV type. The association between CD4+/HIV RNA strata and HPV persistence was statistically significantly smaller (P<.001) than for incident HPV detection. SIL prevalence, incident detection, and persistence had similar associations with CD4+/HIV RNA strata as HPV (above).
  
  
  CONCLUSIONS
  In HIV-positive women, plasma HIV RNA level and CD4+ count in combination appear to have a strong and statistically interactive association with incident detection of HPV, some of which may reflect HPV reactivation (e.g., in sexually inactive women). The more moderate association between HIV coinfection and HPV persistence could partly explain why cervical cancer rates have not reached more epidemic proportions in HIV-positive women.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Ave., Belfer #1308, Bronx, NY 10461, USA. strickle@aecom.yu.edu
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.forename: Melissa
authors.initials: M
authors.lastname: Fazzari
authors.forename: Kathryn
authors.initials: K
authors.lastname: Anastos
authors.forename: Howard
authors.initials: H
authors.lastname: Minkoff
authors.forename: L Stewart
authors.initials: LS
authors.lastname: Massad
authors.forename: Charles
authors.initials: C
authors.lastname: Hall
authors.forename: Melanie
authors.initials: M
authors.lastname: Bacon
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Levine
authors.forename: D Heather
authors.initials: DH
authors.lastname: Watts
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Silverberg
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Schlecht
authors.forename: Sandra
authors.initials: S
authors.lastname: Melnick
authors.forename: Joel M
authors.initials: JM
authors.lastname: Palefsky
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000821:virology*; D000208:Acute Disease; D000328:Adult; D018791:CD4 Lymphocyte Count; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000821:virology*; D015986:Confounding Factors, Epidemiologic; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006678:HIV / Q000235:genetics; D006679:HIV Seropositivity / Q000150:complications* / Q000276:immunology; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D015999:Multivariate Analysis; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000032:analysis; D012107:Research Design; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000821:virology*
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral