HIV-1 Genetic Diversity Among Incident Infections in Mbeya, Tanzania

Abstract

In preparation for vaccine trials, HIV-1 genetic diversity was surveyed between 2002 and 2006 through the Cohort Development study in the form of a retrospective and prospective observational study in and around the town of Mbeya in Tanzania's Southwest Highlands. This study describes the molecular epidemiology of HIV-1 strains obtained from 97 out of 106 incident HIV-1 infections identified in three subpopulations of participants (one rural, two urban) from the Mbeya area. Near full-genome or half-genome sequencing showed a subtype distribution of 40% C, 17% A1, 1% D, and 42% inter-subtype recombinants. Compared to viral subtyping results previously obtained from the retrospective phase of this study, the overall proportion of incident viral strains did not change greatly during the study course, suggesting maturity of the epidemic. A comparison to a current Phase I-II vaccine being tested in Africa shows ∼17% amino acid sequence difference between the gp120 of the vaccine and subtype C incident strains. Phylogenetic and recombinant breakpoint analysis of the incident strains revealed the emergence of CRF41_CD and many unique recombinants, as well as the presence of six local transmission networks most of which were confined to the rural subpopulation. In the context of vaccine cohort selection, these results suggest distinct infection transmission dynamics within these three geographically close subpopulations. The diversity and genetic sequences of the HIV-1 strains obtained during this study will greatly contribute to the planning, immunogen selection, and analysis of vaccine-induced immune responses observed during HIV-1 vaccine trials in Tanzania and neighboring countries.

Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate

“…A total of 93 full-length infectious envelope sequences were isolated from the plasma viral RNA of 52 treatment-naïve, HIV-1-infected patients in Dar es Salaam, Tanzania. The subtype analysis based on the full-length envelope sequences showed that the most abundant ones were identified as the isRFs (34.6%), followed by subtype A1 (28.8%), C (23.1%), and D (13.5%) (Table 1), indicating co-circulating multiple non-B subtypes and isRFs in this region and in good agreement with previous studies (Hoelscher et al, 2001;Vasan et al, 2006;Shao et al, 2014;Billings et al, 2017;Barabona et al, 2019). Testing of the duration of infection by a limiting antigen avidity enzyme immunoassay revealed that 82.7 and 17.3% of the participants were considered to be chronically and recently infected, respectively (Table 1).…”

Molecular epidemiology of a primarily MSM acute HIV‐1 cohort in Bangkok, Thailand and connections within networks of transmission in Asia

“…By way of comparison, in the Nigerian epidemic in which two major subtypes (G and CRF02_AG) co‐circulate, the relative proportion of recombinants is similar to that of the parental subtypes . A high proportion of multi‐subtype recombinants is also seen in the Tanzanian epidemic, in which subtypes A1, C and D co‐circulate . The Thai epidemic has seen the blending of once segregated risk groups, which provides opportunity for multiple exposures in individuals and the conditions for multiple subtypes to recombine.…”

HIV-1 genetic diversity and demographic characteristics in Bulgaria

“…Since previous analyses were limited to pro-RT sequences, it was expected that multiple URFs would be observed once longer env or full-length sequences were obtained. Other countries with comparable diversity [31, 32], displayed high proportions of URF (approaching half of the sequences collected), which should have been apparent within the 37 sequences collected here. Aside from potential sampling bias, the most likely explanation for the low number of URFs is the low prevalence of HIV-1 in Bulgaria, which would minimize the opportunity for super-infection and recombinant generation.…”