Effect of Non-Nucleoside Reverse Transcriptase Inhibitors on Cytokine, Chemokine, and Immunoglobulin Profiles in Serum and Genital Secretions of HIV-Infected Women

Abstract

Non-protease inhibitor-based antiretroviral therapy (ART) is widely accepted as first-line ART in developing countries. Although reverse transcriptase inhibitor-based regimens have been studied in the peripheral blood, no studies have analyzed alterations in cytokine and chemokine levels, together in peripheral blood and genital secretions. Forty HIV-infected women with CD4 cell counts <200 cells/mm(3), asymptomatic, with no genital tract infection, willing to participate in the study, and adhere to ART were enrolled. Cervicovaginal lavage (CVL) was collected in the mid-cycle phase of menstrual cycle. Patients were initiated with reverse transcriptase-based antiretrovirals. Repeat sampling was performed at 24 weeks. Cytokines and chemokines were measured using ultrasensitive ELISA kits. Viral load declined to undetectable levels in 29 patients in the blood and in 33 cases in the CVL. Proinflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha, interleukin-6 [IL-6], IL-1beta) in the serum and CVL showed a significant decrease in mean levels after therapy. IL-2 levels increased significantly whereas IL-12 and (IFN-gamma decreased in both compartments. Mean levels of IL-4 and IL-10 decreased significantly in the serum. There was direct correlation between serum and CVL levels of IL-2 and IL-10. IL-10 had a negative correlation with CD4% at baseline and 6 months of therapy. Mean levels of all alpha- and beta-chemokines decreased in serum after therapy. In CVL, mean levels of MIP-1alpha, RANTES, and IL-8 reduced and SDF-1alpha increased significantly (P value <0.001). Serum levels of all the cytokines, except IL-2, and all chemokines prior to therapy, were significantly higher than healthy controls. In CVL, mean levels of TNF-alpha, IL-6, IL-1beta, IL-12, IFN-gamma, IL-10, RANTES, and IL-8 were significantly higher, whereas IL-2, MIP-1alpha, and MIP-1beta were significantly lower than healthy controls. The mean levels of proinflammatory cytokines and chemokines significantly decreased in serum and CVL after therapy, possibly due to reduced viral load.