EVALUATION OF IMMUNOLOGICAL MARKERS IN CERVICOVAGINAL FLUID OF HIV-INFECTED AND UNINFECTED WOMEN - IMPLICATIONS FOR THE IMMUNOLOGICAL RESPONSE TO HIV IN THE FEMALE GENITAL-TRACT

We analyzed 21 cervicovaginal lavage (CVL) specimens from 19 women par ticipating in the Women's Interagency HIV Study to characterize levels of antibody, cytokine, and complement and to determine associations b etween these levels and stage of the menstrual cycle, HIV status, and the presence of concurrent genital infection and genital dysplasia. Si xteen samples were collected from HIV-infected women and five from hig h-risk HIV-seronegative women. CVL fluid was assayed for levels of IgG , secretory IgA (s-IgA), interleukin 2 (IL-2), IL-10, IL-6, tumor necr osis factor alpha (TNF-alpha), IL-1 beta, interferon gamma (IFN-gamma) , C3, Clq, and C4. Women with HIV were more likely to have cervicovagi nal dysplasia (9/16 vs. 0/5; p = 0.027) but were not more likely to ha ve concurrent vaginal infection (10/16 vs. 2/5; p = 0.38). Antibody, c ytokine, and complement were detectable in all samples, although not a ll samples had measurable IL-10, C3, or C4. HIV-infected women demonst rated a trend toward higher levels of IFN-gamma than did uninfected wo men (p = 0.098); no differences were noted in other parameters. HIV-in fected women with vaginal infections had significantly higher CVL leve ls of IgG (p = 0.023) and IFN-gamma (p = 0.02) than did HIV-infected w omen without genital infections. HIV-infected women with cervicovagina l dysplasia were found to have higher levels of IL-1 beta (p = 0.045) and IFN-gamma (p = 0.039) than those without. Analysis of the HIV-infe cted cohort by CD4 cell count revealed higher levels of IgG and IFN-ga mma in CVL from women with lower CD4 cell counts, although these diffe rences were not statistically significant. Higher levels of proinflamm atory cytokines in CVL fluid of women with genital infection or cervic ovaginal dysplasia may affect local HIV replication and may influence the risk of acquisition or transmission of HIV for women with these un derlying conditions.