Correlation between human immunodeficiency virus type 1 RNA levels in the female genital tract and immune activation associated with ulceration of the cervix

To address the hypothesis that local immune activation resulting from genit al ulceration enhances human immunodeficiency virus type 1 (HIV-1) replicat ion and shedding into the genital tract, paired plasma and cervicovaginal l avage (CVL) samples were obtained from 12 HIV-infected women before and aft er treatment of cervical intraepithelial lesions. Two weeks after treatment , inflammation and ulceration of the cervix were accompanied by major incre ases 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 ea ch), but not plasma. Strong temporal and quantitative correlations were obs erved between concentrations of immunological markers and HIV-1 load in thi s compartment during a 10-week follow-up, Furthermore, in the presence of g enital ulceration, HIV-1 in CVL samples was more readily captured by antibo dies directed against virion-associated HLA-DR, a marker of host-cell activ ation, compared with virus in plasma. We suggest that local immune activati on increases HIV-1 load in genital secretions, potentially increasing the r isk of HIV-1 transmission.