Limiting Hiv Target Cells in the Female Genital Tract by Inducing Immune Quiescence

Abstract

Introduction and Objectives: In excess of 1.5 million new HIV-1 infections and over 800,000 HIV/AIDS-related deaths still occur annually across the globe despite much headway being made in HIV-1 management. Prevention of HIV-1 acquisition is therefore a priority, especially for populations that may be at higher risk of infection. Over the last decade, several avenues for HIV-1 infection have been explored, most targeting deactivation of the virus. The Immune quiescence (I.Q) phenotype, characterised by a low number of HIV target (CD4+CCR5+), a low inflammatory state and reduced T-cell activation in the host, as is observed among HIV Highly exposed sero-negative (HESN) cohorts, has been suggested to be protective against HIV-1 acquisition. Our study aimed to explore the hypothesis that the host immune system can be modulated to induce this I.Q phenotype using oral administration of available, non-stigmatising administered non-steroidal anti-inflammatory drugs, aspirin/acetylsalicylic acid (ASA) and hydroxychloroquine (HCQ) thereby adding to the arsenal available in the HIV-1 prevention toolkit, that does not target the virus. We therefore assessed the change in proportion of HIV target cells and level of T-cell activation among a healthy population after daily oral administration of ASA or HCQ. Study Design and Methodology: HIV negative, healthy women who were non-sex workers from the Pumwani Mother to Child cohort and Baba Dogo clinics in Nairobi, Kenya, were screened and recruited to a randomised, interventional, open labelled trial. In total, 162 participants were screened with being 91 randomised to either study arm of receiving a daily oral dose of either HCQ (200mg/day) or ASA (81mg/day) over a period of six weeks. Peripheral blood and cervical cytobrush samples from the female genital tract (FGT) from which mononuclear cells were extracted, as well as plasma and cervico-vaginal lavage samples were collected at baseline (0....................................................................