Demographics of sources of HIV-1 transmission in Zambia: a molecular epidemiology analysis in the HPTN 071 PopART study

Abstract

Background: In the last decade, universally available antiretroviral therapy (ART) has led to greatly improved health and survival of people living with HIV in sub-Saharan Africa, but new infections continue to appear. The design of effective prevention strategies requires the demographic characterisation of individuals acting as sources of infection, which is the aim of this study.

Methods: Between 2014 and 2018, the HPTN 071 PopART study was conducted to quantify the public health benefits of ART. Viral samples from 7124 study participants in Zambia were deep-sequenced as part of HPTN 071-02 PopART Phylogenetics, an ancillary study. We used these sequences to identify likely transmission pairs. After demographic weighting of the recipients in these pairs to match the overall HIV-positive population, we analysed the demographic characteristics of the sources to better understand transmission in the general population.

Findings: We identified a total of 300 likely transmission pairs. 178 (59·4%) were male to female, with 130 (95% CI 110-150; 43·3%) from males aged 25-40 years. Overall, men transmitted 2·09-fold (2·06-2·29) more infections per capita than women, a ratio peaking at 5·87 (2·78-15·8) in the 35-39 years source age group. 40 (26-57; 13·2%) transmissions linked individuals from different communities in the trial. Of 288 sources with recorded information on drug resistance mutations, 52 (38-69; 18·1%) carried viruses resistant to first-line ART.

Interpretation: HIV-1 transmission in the HPTN 071 study communities comes from a wide range of age and sex groups, and there is no outsized contribution to new infections from importation or drug resistance mutations. Men aged 25-39 years, underserved by current treatment and prevention services, should be prioritised for HIV testing and ART.

Funding: National Institute of Allergy and Infectious Diseases, US President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation, National Institute on Drug Abuse, and National Institute of Mental Health.

Figure 1

Flowchart depicting determination of transmission pairs from recruited participants from the nine Zambian communities

Figure 2

Example transmission pairs and windows From the consensus phylogeny of 5612 full-genome sequences, three transmission pairs are enlarged. Tips for the male individual are in blue and the female in red. Annotations indicate the reconstructed direction of transmission and the estimated time from infection to sampling of the recipient. The first column displays the position of each pair among its immediate neighbours in the consensus tree. The remaining three columns are example phyloscanner windows (coordinates and genes are given) and the within-host phylogenies for the pair in each. Note that the topological direction of transmission is identified by summarising patterns over all windows and thus some individual trees will not match it (eg, row 2, column 4). Tree branches are in units of substitutions per site (see scale bars for each tree).

Figure 3

Characteristics of sources of transmission (A) Age profile (at the estimated time of transmission) of the sources of infection for participants estimated to have been infected during the trial period. Counts were weighted to make the recipient population representative of the HIV-positive population during the trial. (B) For different age and sex demographics, the ratio of the proportion of sources in that group to the proportion in the same group of (top) all HIV-positive individuals or (bottom) all HIV-positive individuals not on ART. Ages are calculated as of July 1, 2017. Shaded bars are 95% CIs determined by non-parametric bootstrap. We identified no male sources in the 13–19 years age group and thus this estimate is omitted. (C) Ratios for the relative contributions of male and female sources by age group (as calculated for panel B). Shaded bars are 95% CIs as before. The bootstrapped confidence intervals for the ≥50 years age group extend upwards to infinity. (D) First-line drug resistance profiles of sources. (E) Proportions of infections from sources residing in a different community from the recipient. ART=antiretroviral therapy.

Figure 4

Combined characteristics of source individuals (A) Distribution of all combinations of four key risk factors among the set of directed opposite-sex pairs determined to have been infected during the trial period. Each bar represents a group of sources whose characteristics are defined by the combination of black dots on the x-axis. Bars are weighted as in previous plots. (B) Pictorial representation of the expected characteristics of 100 sources of transmission. Note that as all transmission is assumed to be heterosexual, the 60 men and 40 women will have infected, respectively, 60 women and 40 men. DR=drug resistance.