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

Abstract

Background: Genital 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 methods: All 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 ≥ 40 copies/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.

Results: 96 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.

Conclusion: Suppressive 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.

Fig 1. Cohort profile.

This flow chart provides information on the number of patients recruited, eligible for antiretroviral therapy and who had viral load and CD4 data available at baseline and at month 12. Patients were classified in groups of genital viral load (GVL) <40 RNA copies/ml and GVL ≥40 copies /mL.

Fig 2. Changes of biological marker levels in the genital compartments between baseline and month 12 among study participants receiving anti-retroviral therapy.

Changes of genital (GVL) and plasma viral loads (PVL), CD4 counts and cytokines levels analysed as continuous variables were compared between baseline and month 12 in patients receiving antiretroviral therapy. Thin broken lines represent the change in immune parameter of a study participant between the two measurement times and the thick solid line in red is the average change in the parameter between the two time points. P values were calculated using the paired t-test and are displayed inside each graph. GVL, PVL and CD4 counts changes were significant, whereas cytokines levels remained comparable at baseline and month 12.