title: Valacyclovir therapy does not reverse herpes-associated alterations in cervical immunology: a randomized, placebo-controlled crossover trial.
abstract: Herpes simplex virus type 2 (HSV-2) infection is associated with a 3-fold increase in the risk of human immunodeficiency virus (HIV) acquisition, perhaps through alterations in mucosal HIV-susceptible target cells. We performed a clinical trial to assess the impact of herpes therapy on cervical immunology in HSV-2-infected, HIV-uninfected women from Africa or the Caribbean who were living in Toronto, Canada. Thirty participants received 1 g of valacyclovir orally each day for 2 months in a randomized double-blind, placebo-controlled, crossover trial. Valacyclovir did not reduce the number of cervical CD4(+) T cells, the number of dendritic cells, or the expression of proinflammatory cytokines and tended to increase the expression of the HIV coreceptor CCR5 and the activation marker CD69. Short-term valacyclovir therapy did not reverse HSV-2-associated alterations in genital immunology. Clinical Trials Registration. NCT00946556.
authors.affiliation: Department of Medicine Department of Immunology.
authors.forename: Tae Joon
authors.initials: TJ
authors.lastname: Yi
authors.affiliation: Department of Medicine Department of Immunology.
authors.forename: Brett
authors.initials: B
authors.lastname: Shannon
authors.affiliation: Women's Health in Women's Hands Community Health Centre, Toronto, Canada.
authors.forename: Lisungu
authors.initials: L
authors.lastname: Chieza
authors.affiliation: Dalla Lana School of Public Health, University of Toronto.
authors.forename: DeSheng
authors.initials: D
authors.lastname: Su
authors.affiliation: Women's Health in Women's Hands Community Health Centre, Toronto, Canada.
authors.forename: Megan
authors.initials: M
authors.lastname: Saunders
authors.affiliation: Women's Health in Women's Hands Community Health Centre, Toronto, Canada.
authors.forename: Wangari
authors.initials: W
authors.lastname: Tharao
authors.affiliation: Department of Medicine Department of Immunology.
authors.forename: Sanja
authors.initials: S
authors.lastname: Huibner
authors.affiliation: Dalla Lana School of Public Health, University of Toronto.
authors.forename: Robert
authors.initials: R
authors.lastname: Remis
authors.affiliation: Dalla Lana School of Public Health, University of Toronto.
authors.forename: Janet
authors.initials: J
authors.lastname: Raboud
authors.affiliation: Department of Medicine Department of Immunology.
authors.forename: Rupert
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002170:Canada; D002584:Cervix Uteri / Q000276:immunology* / Q000473:pathology; D018592:Cross-Over Studies; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006678:HIV; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D007958:Leukocyte Count; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D010919:Placebos; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir
keywords: HIV; HSV-2; STI; acyclovir; cervix; co-infections; female genital tract; mucosal immunology; susceptibility; valacyclovir