Evidence of HIV-1 Genital Shedding after One Year of Antiretroviral Therapy in Females Recently Diagnosed in Bamako, Mali

Abstract

Little is known about the dynamic of HIV-1 shedding and resistance profiles in the female genital reservoir after antiretroviral therapy (ART) initiation in resource-limited countries (RLCs), which is critical for evaluating the residual sexual HIV-1 transmission risk. The present study aimed to evaluate the efficacy of 1 year duration ART at blood and genital levels in females newly diagnosed for HIV-1 from three centers in Bamako, Mali. Seventy-eight consenting females were enrolled at the time of their HIV-1 infection diagnosis. HIV-1 RNA loads (Abbott Real-Time HIV-1 assay) were tested in blood and cervicovaginal fluids (CVF) before and 12 months after ART initiation. Primary and acquired resistances to ART were evaluated by Viroseq^TM HIV-1 genotyping assay. The vaginal microbiota was analyzed using IonTorrent^TM NGS technology (Thermo Fisher Scientific). Proportions of primary drug resistance mutations in blood and CVF were 13.4% and 25%, respectively. Discrepant profiles were observed in 25% of paired blood/CVF samples. The acquired resistance rate was 3.1% in blood. At month 12, undetectable HIV-1 RNA load was reached in 84.6% and 75% of blood and CVF samples, respectively. A vaginal dysbiosis was associated with HIV RNA shedding. Our findings emphasize the need of reinforcing education to improve retention in care system, as well as the necessity of regular virological monitoring before and during ART and of implementing vaginal dysbiosis diagnosis and treatment in RLCs.

Keywords: HIV-1; Mali; antiretroviral therapy; genital reservoir; microbiota; resistance.

Figure 1

Phylogenetic tree based on reverse-transcriptase and protease genes of 84 samples obtained from blood (BL, n = 60) and cervicovaginal fluid (CVF, n = 24). Strains from the same patient exhibiting identical sequences are shown in a circle (bootstrap values above 96%).

Figure 2

Scatter/box plot showing the viral loads in CVF and blood before and after 12 months of ART; **** p < 0.0001. Dashed line: threshold of viral load detection.

Figure 3

Cervicovaginal microbiota analysis in six patients according to HIV viral load in CVF, before and 12 months after ART initiation.