Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women.

Pascale Ondoa,John Rusine,Janneke Van De Wijgert,Neeltje Kootstra,Suzanne Jurriaans,Rene Lutter,Etienne Karita,Raju Gautam,Alan Landay

doi:10.1371/journal.pone.0127201

Abstract

BackgroundGenital viral load (GVL) is the main determinant of sexual transmission of human immune-deficiency virus (HIV). The effect of antiretroviral therapy (ART) on local cervico-vaginal immunological factors associated with GVL is poorly described. We aimed to identify the risk factors of detectable GVL, and the impact of ART on HIV genital shedding and its correlates in a cohort of HIV-infected women, attending HIV care in Kigali, Rwanda.Materials and MethodsAll participants were evaluated for GVL, plasma viral load (PVL), CD4 count, various sexually-transmitted infections (STIs) at baseline and at month 12. Genital concentration of 19 cytokines and mRNA expression of APOBEC3G and BST2, two host HIV restriction factors, were evaluated at baseline in all participants. Cytokine levels were re-assessed at month 12 only in participants eligible for ART at baseline. Risk factors of GVL ≥40copies/mL at baseline and month 12 were assessed using logistic regression. Effect of 12-month ART on various local and systemic immunological parameters was examined using a paired t-test and McNemar as appropriate.Results96 of the 247 women enrolled in the study were eligible for ART. After 12 months of ART, PVL and GVL decreased to undetectable level in respectively 74 and 88% of treated participants. ART did not affect cytokine levels. HIV genital shedding occurred only when PVL was detectable. At baseline, GVL was independently associated with IL-1β after controlling for PVL, age and N. gonorrhea infection (95% CI 1.32-2.15) and at month 12 with MIP-1β (95% CI 0.96-21.32) after controlling for baseline GVL, PVL and month 12 IL-8.ConclusionSuppressive ART does not necessarily reduce genital level of immune activation. Minimizing all conditions favoring genital inflammation, including active detection and treatment of STIs, might reduce the risk of HIV transmission as supplement to the provision of potent ART.

Highlights

Sub-Saharan Africa bears 70% of the worldwide prevalence of human immunedeficiency virus (HIV) infections, with the majority of new infections occurring in women [1]
After 12 months of antiretroviral therapy (ART), plasma viral load (PVL) and Genital viral load (GVL) decreased to undetectable level in respectively 74 and 88% of treated
HIV genital shedding has been demonstrated to be primarily associated with the HIV RNA concentration in plasma (referred to as the plasma viral load (PVL)) [3,4,5] and to depend on various other general or local factors [6]

Summary

Introduction

Sub-Saharan Africa bears 70% of the worldwide prevalence of HIV infections, with the majority of new infections occurring in women [1]. HIV genital shedding has been demonstrated to be primarily associated with the HIV RNA concentration in plasma (referred to as the plasma viral load (PVL)) [3,4,5] and to depend on various other general or local factors [6]. These factors include, among others, local inflammation (for example, inflammation caused by sexually transmitted co-infections), hormonal changes associated with the menstrual cycle, pregnancy or contraception, and peripheral or mucosal CD4 count [7,8,9,10,11,12]. We aimed to identify the risk factors of detectable GVL, and the impact of ART on HIV genital shedding and its correlates in a cohort of HIV-infected women, attending HIV care in Kigali, Rwanda

Objectives

Methods

Results

Conclusion