Relationship Of Th1/Th2 Cytokine Ratio and Haart Type in Pregnant Women with Intermediate Vaginal Flora in Kisumu, Kenya.

Abstract

Most studies have linked protease inhibitor (PI) based highly active antiretroviral therapy (HAART) to spontaneous preterm birth (sPB) without explaining how. We hypothesized that alteration in genital tract flora caused by HAART may cause changes in local cytokine profile which may further result in sPB. The aim of this study was to determine association between Non-efavirenz based HAART, particularly PI based HAART, and Th1/Th2 cytokine ratio in pregnant women with intermediate vaginal flora (IVF) in Kisumu, Kenya. The study was carried out at Lumumba sub county hospital. Willing 76 pregnant women who started HAART on or before the first trimester were enrolled after signing informed consent forms. Using formatted questionnaire participants were interviewed on demographic, clinical and behavioral information. High vaginal swabs for diagnosis of abnormal vaginal flora (AVF), venous blood and lavage for IL 1β and IL 6 assay were collected in the second trimester and at the same time from each participant. Fisher’s Exact Chi square test and multinomial logistic regression were used to determine the association of AVF with HAART and participants characteristics. Eleven (11) participants out of the 76 had IVF and in 4 of the 11 there was positive independent association between IVF and Non-efavirenz based HAART. The 4 were cases and the remaining 7 control. Enzyme linked immunoassay (ELISA) was used to assay IL 1β and IL 6 in serum and cervico-vaginal lavage (CVL) in the 11 participants. Th1/Th2 cytokine ratio was taken as ratio of IL 1β to IL 6 concentration and Mann-Whitney U test used for comparison of Th1/Th2 cytokine ratio and concentration of IL 1β and IL 6 in HAART categories. In CVL IL1β concentration was statistically significantly higher in pregnant women on non efavirenz HAART than the pregnant women on efavirenz HAART (U = 1.00, p = 0.012). This was replicated in PI based HAART against efavirenz based HAART (U = 0.00, p = 0.017). On the other hand Th1/Th2 cytokine ratio in CVL was significantly statistically higher in pregnant women on non efavirenz based HAART than the pregnant women on efavirenz based HAART (U = 3.00, p = 0.042). Which was again replicated in PI based HAART against efavirenz based HAART (U = 0.00, p = 0.017). Since sPB is mostly correlated to local genital biomarkers compared to systemic biomarkers, studying Th1/Th2 cytokine ratio in genital tract may better explain what triggers sPB than studying systemic cytokine profiles.