Markers of local immunity in cervico-vaginal secretions of HIV infected women: implications for HIV shedding

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Abstract
Objectives: To link local proinflammatory cytokines with HIV related nucleic acids in cervico-vaginal secretions and the factors associated with them. Methods: An observational study on 60 HIV positive women attending the department of obstetrics and gynaecology, University of Pavia, Italy. HIV-1 RNA in plasma, proviral HIV-1-DNA, cell associated and cell free HIV-1 RNA in cervico-vaginal secretions were evaluated by competitive polymerase chain reaction (c-PCR) and reverse transcriptase PCR (cRT-PCR). IL-1β, IL-6, and TNF-α were measured by ELISA in cervico-vaginal lavages. Multiple regression analysis on ordinal categorical variables was used to test for the simultaneous associations of clinical and microbiological variables on quartiles of cytokine concentrations in lavage samples. Results: Proviral HIV-1 DNA, cell associated and cell free HIV-1 RNA were detected in 76.7% (46/60), 70% (42/60), and 71.7% (43/60) of the patients, respectively. IL-1β concentration was directly correlated with proviral HIV-DNA (Spearman rho = 0.35, p = 0.01) and cell associated HIV-RNA levels (Spearman rho = 0.263, p = 0.05). IL-1β concentration (153.9 pg/ml) was higher (pConclusions: Local immune activation may modulate HIV-1 shedding in cervico-vaginal secretion with possible influence on vaginal physiology and host defence. Pharmacological agents lowering HIV-1 replication cause a shift to a pattern of cytokine production which seems less favourable to the transmission of the disease.