Research Article: HIV-1 diversity among young women in rural South Africa: HPTN 068

Date Published: July 5, 2018

Publisher: Public Library of Science

Author(s): Mariya V. Sivay, Sarah E. Hudelson, Jing Wang, Yaw Agyei, Erica L. Hamilton, Amanda Selin, Ann Dennis, Kathleen Kahn, F. Xavier Gomez-Olive, Catherine MacPhail, James P. Hughes, Audrey Pettifor, Susan H. Eshleman, Mary Kathryn Grabowski, Dimitrios Paraskevis.


South Africa has one of the highest rates of HIV-1 (HIV) infection world-wide, with the highest rates among young women. We analyzed the molecular epidemiology and evolutionary history of HIV in young women attending high school in rural South Africa.

Samples were obtained from the HPTN 068 randomized controlled trial, which evaluated the effect of cash transfers for school attendance on HIV incidence in women aged 13–20 years (Mpumalanga province, 2011–2015). Plasma samples from HIV-infected participants were analyzed using the ViroSeq HIV-1 Genotyping assay. Phylogenetic analysis was performed using 200 pol gene study sequences and 2,294 subtype C reference sequences from South Africa. Transmission clusters were identified using Cluster Picker and HIV-TRACE, and were characterized using demographic and other epidemiological data. Phylodynamic analyses were performed using the BEAST software.

The study enrolled 2,533 young women who were followed through their expected high school graduation date (main study); some participants had a post-study assessment (follow-up study). Two-hundred-twelve of 2,533 enrolled young women had HIV infection. HIV pol sequences were obtained for 94% (n = 201/212) of the HIV-infected participants. All but one of the sequences were HIV-1 subtype C; the non-C subtype sequence was excluded from further analysis. Median pairwise genetic distance between the subtype C sequences was 6.4% (IQR: 5.6–7.2). Overall, 26% of study sequences fell into 21 phylogenetic clusters with 2–6 women per cluster. Thirteen (62%) clusters included women who were HIV-infected at enrollment. Clustering was not associated with study arm, demographic or other epidemiological factors. The estimated date of origin of HIV subtype C in the study population was 1958 (95% highest posterior density [HPD]: 1931–1980), and the median estimated substitution rate among study pol sequences was 1.98×10-3 (95% HPD: 1.15×10-3–2.81×10-3) per site per year.

Phylogenetic analysis suggests that multiple HIV subtype C sublineages circulate among school age girls in South Africa. There were no substantive differences in the molecular epidemiology of HIV between control and intervention arms in the HPTN 068 trial.

Partial Text

South Africa has one of the highest rates of human immunodeficiency virus type 1 (HIV) infection in the world [1]. The highest HIV prevalence rates have been reported in the KwaZulu-Natal and Mpumalanga provinces (18% and 15.2%, respectively; ages 15–49; 2016) [2]. Adolescent girls and young women are at increased risk of HIV infection. In 2012, an estimated four million women in South Africa aged 15 and over were living with HIV/AIDS, with HIV prevalence rates of 5.6% among those aged 15–19 and 17.4% among those aged 20–24 [1]. In this region, young women acquire HIV infection earlier and have higher HIV incidence rates compared to young men [3, 4]. Several studies have evaluated HIV infection among high school students in South Africa. Studies of young women attending high-school in rural KwaZulu-Natal found higher HIV prevalence and incidence among those women than their male peers [3, 5].

In this study, we analyzed indirect female-to-female HIV transmission chains among young women with HIV subtype C infection who were attending high school in rural South Africa. All but one of the 201 HPTN 068 participants with genotyping results had HIV subtype C infection; one participant had HIV subtype A infection. Phylogenetic analysis revealed small distinct HIV transmission clusters among study sequences scattered across the subset of subtype C reference sequences from South Africa. Clustering was not statistically significantly associated with demographic and select epidemiological characteristics of study participants. Results in this report and results of another study from the same region (Bushbuckridge sub-district, Mpumalanga province) [43] indicate that there are multiple HIV subtype C sublineages circulating in the population of this area.




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