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.

Keywords: HIV genetics; HIV transmission; epidemiology; phylogenetics; vaccines.

FIG. 1.

Comparison of pure subtype and recombinant virus distribution between incident and prevalent infection phases of the CODE study. The proportions of HIV-1 strains observed among the three subpopulations within the incident infections are shown in (a) and the prevalent infections in (b). The crosshatched areas represent the fraction of each strain type that was found among the urban subpopulations. CODE, cohort development. Color images available online at www.liebertpub.com/aid

FIG. 2.

Phylogenetic relationships and transmission networks between incident infection strains. Neighbor-joining tree showing the phylogenetic relationships between incident infection strains from all three subpopulations was constructed using the full-length genomes and pure subtype and recombinant reference sequences from the prevalent infection phase of this study as well as regionally relevant strains. Pure subtype incident infection strains are shown in blue, recombinant incident strains are shown in red, and reference strains are shown in black. Tree segments corresponding with pure subtype reference strains are demarked (gray bar) and labeled according to their respective subtypes. The incident strains that belong to proposed transmission networks were identified as having a pairwise genetic distance of <1.5% when comparing prot-RT (HXB2 2262-3290), and are demarked with colored bars and labeled with the participant's gender. Meaningful bootstrap values at relevant nodes are shown. The scale bar indicates a genetic distance of 10%. Color images available online at www.liebertpub.com/aid

FIG. 3.

Genome structures of the 40 HIV-1 recombinant strains identified during the CODE incident infection study. Incident recombinant genomes are depicted in relation to the HXB2 reference strain. The colored segments represent the predicted parent subtype based on recombinant breakpoint analysis. Subtype A1 is shown in red, A2 in pink, C in yellow, and D in blue. Color images available online at www.liebertpub.com/aid

FIG. 4.

CRF41_CD genome structure and phylogenetic analysis of subgenome fragments. The recombinant genome of CRF41_CD is depicted in relation to the HXB2 reference strain (top). Subgenomic fragments corresponding to parent subtype C are shown in yellow and subtype D in blue. The phylogenetic relationship between the full-length CR41_CD strains and subtype reference strains is shown (left). Confirmation of the parent subtypes of the subgenomic fragments is shown using neighbor-joining trees (center) constructed from the corresponding numbered fragments of CRF41_CD (top) and the reference strains (left). Meaningful bootstrap values at relevant nodes are shown. The scale bar indicates a genetic distance of 10%. Color images available online at www.liebertpub.com/aid