The Role of Phylogenetics in Discerning HIV-1 Mixing among Vulnerable Populations and Geographic Regions in Sub-Saharan Africa: A Systematic Review

Abstract

To reduce global HIV-1 incidence, there is a need to understand and disentangle HIV-1 transmission dynamics and to determine the geographic areas and populations that act as hubs or drivers of HIV-1 spread. In Sub-Saharan Africa (sSA), the region with the highest HIV-1 burden, information about such transmission dynamics is sparse. Phylogenetic inference is a powerful method for the study of HIV-1 transmission networks and source attribution. In this review, we assessed available phylogenetic data on mixing between HIV-1 hotspots (geographic areas and populations with high HIV-1 incidence and prevalence) and areas or populations with lower HIV-1 burden in sSA. We searched PubMed and identified and reviewed 64 studies on HIV-1 transmission dynamics within and between risk groups and geographic locations in sSA (published 1995–2021). We describe HIV-1 transmission from both a geographic and a risk group perspective in sSA. Finally, we discuss the challenges facing phylogenetic inference in mixed epidemics in sSA and offer our perspectives and potential solutions to the identified challenges.

The Role of Phylogenetics in Unravelling Patterns of HIV Transmission towards Epidemic Control: The Quebec Experience (2002–2020)

“…In this issue of Viruses, our study alongside that of Parks et al shows how phylogenetics can assist in unravelling an in-depth sampled epidemic spreading among MSM, PWID, and HET groups in Quebec [ 32 ]. Nduva et al and Bbosa et al provide excellent studies describing the role of phylogenetics in describing viral spread in different regions of Africa [ 5 , 47 ]. For epidemic control in the next decade, there is a need to develop improved strategies to combine phylogenetic and epidemiological data to address and control for missed sampling [ 38 ].…”

“…In Western world settings, concentrated HIV-1 subtype B epidemics circulate in key vulnerable populations, including Men having Sex with Men (MSM), People Who Inject Drugs (PWID), and marginalized Heterosexual groups [ 2 , 3 , 4 ]. In Africa and Asia, generalized Heterosexual (HET) epidemics have diversified to include 10 HIV-1 subtypes and over 40 circulating recombinant forms [ 5 ]. Human migration has led to changing demographics, wherein non-B subtypes now account for 20–60% of new infections in the Americas and Europe [ 4 , 6 , 7 ].…”

Phylogeographic Assessment Reveals Geographic Sources of HIV-1 Dissemination Among Men Who Have Sex With Men in Kenya

“…For each subtype, monophyletic clades with aLRT-SH support ≥0.9 and which were dominated (≥80%) by Kenyan sequences (compared to reference sequences) were defined as Kenyan HIV-1 clusters (Hassan et al, 2017). Clusters were classified based on the number of sequences per cluster into dyads (2 sequences), networks (3-14 sequences), and large clusters (>14 sequences) (Esbjörnsson et al, 2016;Nduva et al, 2020;Abidi et al, 2021).…”

“…In sub-Saharan Africa, the HIV-1 epidemic among men who have sex with men (MSM) has only recently received attention—and the role of MSM in HIV-1 transmission has been acknowledged ( Beyrer et al, 2010 ; Sanders et al, 2015a ; Nduva et al, 2021 ). In Kenya, the national HIV-1 prevalence is 4.9% in the adult population, but is threefold higher in MSM than in heterosexual men ( Kenya National Aids Control Council, 2019 ; National AIDS and STI Control Programme [NASCOP], 2020 ).…”

“…HIV-1 transmission dynamics can be assessed by linking sociodemographic, clinical, and behavioral data with HIV-1 sequence data through phylogenetics ( Brenner et al, 2007 ; Volz et al, 2013 ; Bruhn et al, 2014 ; Frentz et al, 2014 ; Pybus et al, 2015 ; Esbjörnsson et al, 2016 ; Poon et al, 2016 ; Ratmann et al, 2016 ; Hassan et al, 2017 ; Sallam et al, 2017 ). While limited HIV-1 sequences have been obtained from blood plasma from MSM living with HIV in Kenya, phylogenetic determination of patterns of HIV-1 transmission among Kenyan MSM suggests extensive MSM HIV-1 clustering (and infrequent HIV-1 mixing between MSM and presumed heterosexuals in the general population) ( Bezemer et al, 2014 ; Hassan et al, 2018 ; Nduva et al, 2020 , 2021 , in press ). In addition, a phylogenetic study in 2013 reported frequent HIV-1 gene flow between MSM in Coastal Kenya and Nairobi—albeit with small sample size and limited geographic coverage ( Bezemer et al, 2014 ).…”