Mapping of HIV-1C Transmission Networks Reveals Extensive Spread of Viral Lineages Across Villages in Botswana Treatment-as-Prevention Trial

Abstract

Background: Phylogenetic mapping of HIV-1 lineages circulating across defined geographical locations is promising for better understanding HIV transmission networks to design optimal prevention interventions.

Methods: We obtained near full-length HIV-1 genome sequences from people living with HIV (PLWH), including participants on antiretroviral treatment in the Botswana Combination Prevention Project, conducted in 30 Botswana communities in 2013-2018. Phylogenetic relationships among viral sequences were estimated by maximum likelihood.

Results: We obtained 6078 near full-length HIV-1C genome sequences from 6075 PLWH. We identified 984 phylogenetically distinct HIV-1 lineages (molecular HIV clusters) circulating in Botswana by mid-2018, with 2-27 members per cluster. Of these, dyads accounted for 62%, approximately 32% (n = 316) were found in single communities, and 68% (n = 668) were spread across multiple communities. Men in clusters were approximately 3 years older than women (median age 42 years, vs 39 years; P < .0001). In 65% of clusters, men were older than women, while in 35% of clusters women were older than men. The majority of identified viral lineages were spread across multiple communities.

Conclusions: A large number of circulating phylogenetically distinct HIV-1C lineages (molecular HIV clusters) suggests highly diversified HIV transmission networks across Botswana communities by 2018.

Keywords: Botswana; HIV-1 clusters; transmission network; viral lineages.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Spread of HIV-1C lineages across Botswana. The extent of HIV-1C spread between and across communities in Botswana is shown. A total of 984 phylogenetically distinct viral lineages were identified in 30 villages/communities participating in the Botswana Combination Prevention Project study in 2013–2018. Only viral lineage spread between multiple communities are presented, as color lines. Each color line indicates a separate viral lineage. Viral lineages circulating in single communities (not shared between communities) are not shown.

Figure 2.

Heatmap of identified viral links. The enumerated links (edges) within molecular HIV-1C clusters demonstrate the spread of identified phylogenetically distinct HIV-1C lineages across (within and between) 30 Botswana communities participating in the Botswana Combination Prevention Project study. Cross-tabulation in the heatmap indicate the number of shared molecular HIV clusters.

Figure 3.

Potential associations (per village/community participating in the Botswana Combination Prevention Project study). A, Potential associations between the number of identified HIV-1C lineages and the number of analyzed near full-length HIV-1C genome sequences. B, Potential associations between the number of identified HIV-1C lineages and HIV-1 prevalence. C, Potential associations between genotyping density and the number of analyzed near full-length HIV-1C genome sequences. D, Potential associations between genotyping density and HIV-1 prevalence. Squares represent communities; linear regression lines indicate estimated Spearman rank correlation; shadings show 95% confidence intervals.

Figure 4.

Breadth of viral lineage spread across communities. The number of communities in which HIV-1C lineages were detected is plotted against cluster size. Boxplots and jittered dots indicate distribution of actual spread of identified viral lineages. Red lines within boxplots show median of communities per cluster size.

Figure 5.

Age distribution density plots. Median age per group is depicted by a vertical dash line. A, Distribution of age among clustered participants by sex. B, Distribution of age in a subset of clusters where men were older than women. C, Distribution of age in a subset of clusters where women were older than men.