title: Increased susceptibility to vaginal simian/human immunodeficiency virus transmission in pig-tailed macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.
abstract: BACKGROUND
  Sexually transmitted infections (STIs) are associated with an increased risk of human immunodeficiency virus (HIV) infection, but their biological effect on HIV susceptibility is not fully understood.
  
  
  METHODS
  Female pig-tailed macaques inoculated with Chlamydia trachomatis and Trichomonas vaginalis (n = 9) or medium (controls; n = 7) were repeatedly challenged intravaginally with SHIVSF162p3. Virus levels were evaluated by real-time polymerase chain reaction, plasma and genital cytokine levels by Luminex assays, and STI clinical signs by colposcopy.
  
  
  RESULTS
  Simian/HIV (SHIV) susceptibility was enhanced in STI-positive macaques (P = .04, by the log-rank test; relative risk, 2.5 [95% confidence interval, 1.1-5.6]). All STI-positive macaques were SHIV infected, whereas 3 controls (43%) remained uninfected. Moreover, relative to STI-negative animals, SHIV infections occurred earlier in the menstrual cycle in STI-positive macaques (P = .01, by the Wilcoxon test). Levels of inflammatory cytokines (interferon γ, interleukin 6, and granulocyte colony-stimulating factor [G-CSF]) were higher in STI-positive macaques during STI inoculation and SHIV exposure periods (P ≤ .05, by the Wilcoxon test).
  
  
  CONCLUSIONS
  C. trachomatis and T. vaginalis infection increase the susceptibility to SHIV, likely because of prolonged genital tract inflammation. These novel data demonstrate a biological link between these nonulcerative STIs and the risk of SHIV infection, supporting epidemiological associations of HIV and STIs. This study establishes a macaque model for studies of high-risk HIV transmission and prevention.
authors.affiliation: Division of HIV/AIDS Prevention.
authors.forename: Tara R
authors.initials: TR
authors.lastname: Henning
authors.affiliation: Division of HIV/AIDS Prevention.
authors.forename: Katherine
authors.initials: K
authors.lastname: Butler
authors.affiliation: Division of HIV/AIDS Prevention.
authors.forename: Debra
authors.initials: D
authors.lastname: Hanson
authors.affiliation: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Gail
authors.initials: G
authors.lastname: Sturdevant
authors.affiliation: Total Solutions, Atlanta, Georgia.
authors.forename: Shanon
authors.initials: S
authors.lastname: Ellis
authors.affiliation: Division of HIV/AIDS Prevention.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Sweeney
authors.affiliation: Division of HIV/AIDS Prevention.
authors.forename: James
authors.initials: J
authors.lastname: Mitchell
authors.affiliation: Division of HIV/AIDS Prevention.
authors.forename: Frank
authors.initials: F
authors.lastname: Deyounks
authors.affiliation: Division of STD Prevention.
authors.forename: Christi
authors.initials: C
authors.lastname: Phillips
authors.affiliation: Division of STD Prevention.
authors.forename: Carol
authors.initials: C
authors.lastname: Farshy
authors.affiliation: Division of STD Prevention.
authors.forename: Yetunde
authors.initials: Y
authors.lastname: Fakile
authors.affiliation: Division of STD Prevention.
authors.forename: John
authors.initials: J
authors.lastname: Papp
authors.affiliation: Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention.
authors.forename: W
authors.initials: W
authors.lastname: Evan Secor
authors.affiliation: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Harlan
authors.initials: H
authors.lastname: Caldwell
authors.affiliation: Department of Obstetrics and Gynecology, University of Washington, Seattle.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Patton
authors.affiliation: Division of HIV/AIDS Prevention.
authors.forename: Janet M
authors.initials: JM
authors.lastname: McNicholl
authors.affiliation: Division of HIV/AIDS Prevention.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kersh
mesh_terms: D000818:Animals; D002584:Cervix Uteri / Q000382:microbiology / Q000469:parasitology / Q000473:pathology; D002690:Chlamydia Infections / Q000150:complications*; D002692:Chlamydia trachomatis; D060085:Coinfection / Q000276:immunology*; D003127:Colposcopy; D005260:Female; D008254:Macaca nemestrina; D012307:Risk Factors; D012749:Sexually Transmitted Diseases / Q000150:complications; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014247:Trichomonas Vaginitis / Q000150:complications*; D014246:Trichomonas vaginalis
keywords: Chlamydia; HIV risk; HIV susceptibility model; STI or STD; Trichomonas; macaque; menstrual cycle
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