title: Correlation between human immunodeficiency virus type 1 RNA levels in the female genital tract and immune activation associated with ulceration of the cervix.
abstract: To address the hypothesis that local immune activation resulting from genital ulceration enhances human immunodeficiency virus type 1 (HIV-1) replication and shedding into the genital tract, paired plasma and cervicovaginal lavage (CVL) samples were obtained from 12 HIV-infected women before and after treatment of cervical intraepithelial lesions. Two weeks after treatment, inflammation and ulceration of the cervix were accompanied by major increases in mean concentrations of HIV-1 RNA (200-fold), tumor necrosis factor-alpha, interleukin 6, and soluble markers shed by activated lymphocytes and macrophages (sCD25 and sCD14, respectively) in CVL samples (P<.01 for each), but not plasma. Strong temporal and quantitative correlations were observed between concentrations of immunological markers and HIV-1 load in this compartment during a 10-week follow-up. Furthermore, in the presence of genital ulceration, HIV-1 in CVL samples was more readily captured by antibodies directed against virion-associated HLA-DR, a marker of host-cell activation, compared with virus in plasma. We suggest that local immune activation increases HIV-1 load in genital secretions, potentially increasing the risk of HIV-1 transmission.
authors.affiliation: Tuberculosis and Mycobacteriology Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. sil3@cdc.gov
authors.forename: S D
authors.initials: SD
authors.lastname: Lawn
authors.forename: S
authors.initials: S
authors.lastname: Subbarao
authors.forename: T C
authors.initials: TC
authors.lastname: Wright
authors.forename: T
authors.initials: T
authors.lastname: Evans-Strickfaden
authors.forename: T V
authors.initials: TV
authors.lastname: Ellerbrock
authors.forename: J L
authors.initials: JL
authors.lastname: Lennox
authors.forename: S T
authors.initials: ST
authors.lastname: Butera
authors.forename: C E
authors.initials: CE
authors.lastname: Hart
mesh_terms: D000328:Adult; D005260:Female; D005836:Genitalia, Female / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014456:Ulcer / Q000276:immunology / Q000821:virology*; D002577:Uterine Cervical Diseases / Q000276:immunology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000628:therapy / Q000821:virology
chemical_list: D006684:HLA-DR Antigens; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D012367:RNA, Viral; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha