title: Genital tract viral load in HIV Type 1-positive women correlates with specific cytokine levels in cervical-vaginal secretions but is not a determinant of infectious virus or anti-HIV activity.
abstract: As the AIDS epidemic continues with women being disproportionately affected, it is crucial to understand factors that predict the risk of heterosexual HIV-1 transmission. We investigated whether genital tract viral load (GTVL) in cervical-vaginal lavages (CVL) from HIV-1-positive women with moderately low CD4 T cell counts correlates with cytokine levels, antimicrobial concentrations, and intrinsic anti-HIV activity. CVL were collected from 19 HIV-1-positive women with moderately low CD4 T cell counts [mean 381 cells/mm(3) (227-536 cells/mm(3))]. None of the women was on antiretroviral therapy. The women were categorized into those with detectable GTVL or those with undetectable GTVL (detectable GTVL RNA levels > 400 copies/ml). Women were also categorized according to bacterial vaginosis (BV) status irrespective of GTVL. The TZM-bl assay was used to determine the presence of infectious virus and anti-HIV activity. Significantly higher levels of RANTES, Eotaxin, Fractalkine, IL-1α, IL-6, MCP-1, MIP1β, MIP1α, TNF-α, and GM-CSF were observed in women with detectable GTVL compared to women with undetectable GTVL. No significant differences were observed in the following cytokines and chemokines: G-CSF, IL-1RA, IL-8, and IP-10. GTVL did not correlate either with antimicrobials known to have anti-HIV activity or with the presence of infectious virus. BV status did not have a significant effect on anti-HIV activity. These findings further our understanding of the role of GTVL in determining the cytokine and chemokine milieu in the female reproductive tract.
authors.affiliation: Department of Physiology and Neurobiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. lucy.r.mukura.gr@dartmouth.edu
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Mukura
authors.forename: Mimi
authors.initials: M
authors.lastname: Ghosh
authors.forename: John V
authors.initials: JV
authors.lastname: Fahey
authors.forename: Susan
authors.initials: S
authors.lastname: Cu-Uvin
authors.forename: Charles R
authors.initials: CR
authors.lastname: Wira
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000635:transmission / Q000821:virology*; D000328:Adult; D018791:CD4 Lymphocyte Count; D002584:Cervix Uteri / Q000378:metabolism / Q000821:virology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015497:HIV-1; D006801:Humans; D008875:Middle Aged; D012367:RNA, Viral; D014621:Vagina / Q000378:metabolism / Q000821:virology*; D044364:Vaginal Douching; D019562:Viral Load
chemical_list: D016207:Cytokines; D012367:RNA, Viral