Molecular Epidemiology and Transmission Dynamics of Recent and Long-Term HIV-1 Infections in Rural Western Kenya

Abstract

Objective: To identify unique characteristics of recent versus established HIV infections and describe sexual transmission networks, we characterized circulating HIV-1 strains from two randomly selected populations of ART-naïve participants in rural western Kenya.

Methods: Recent HIV infections were identified by the HIV-1 subtype B, E and D, immunoglobulin G capture immunoassay (IgG BED-CEIA) and BioRad avidity assays. Genotypic and phylogenetic analyses were performed on the pol gene to identify transmitted drug resistance (TDR) mutations, characterize HIV subtypes and potential transmission clusters. Factors associated with recent infection and clustering were assessed by logistic regression.

Results: Of the 320 specimens, 40 (12.5%) were concordantly identified by the two assays as recent infections. Factors independently associated with being recently infected were age ≤19 years (P = 0.001) and history of sexually transmitted infections (STIs) in the past six months (P = 0.004). HIV subtype distribution differed in recently versus chronically infected participants, with subtype A observed among 53% recent vs. 68% chronic infections (p = 0.04) and subtype D among 26% recent vs. 12% chronic infections (p = 0.012). Overall, the prevalence of primary drug resistance was 1.16%. Of the 258 sequences, 11.2% were in monophyletic clusters of between 2-4 individuals. In multivariate analysis factors associated with clustering included having recent HIV infection P = 0.043 and being from Gem region P = 0.002.

Conclusions: Recent HIV-1 infection was more frequent among 13-19 year olds compared with older age groups, underscoring the ongoing risk and susceptibility of younger persons for acquiring HIV infection. Our findings also provide evidence of sexual networks. The association of recent infections with clustering suggests that early infections may be contributing significant proportions of onward transmission highlighting the need for early diagnosis and treatment as prevention for ongoing prevention. Larger studies are needed to better understand the structure of these networks and subsequently implement and evaluate targeted interventions.

Fig 1. Distribution of HIV-1 subtypes among participants, by recency of infection, Western Kenya, October 2003-May 2005.

(A) Long term (>239 days) (B) recent infections (≤239 days) (Fig 1B). A, C, D, G represent pure subtypes while AD, AC, CD are unique recombinant forms, CRF; Complex recombinants forms.

Fig 2. HIV-1 transmission clusters among heterosexuals in the Gem and Asembo region of Western Kenya.

Phylogenetic tree showing HIV-1 transmission clusters in the Gem and Asembo region. The highlighted tree nodes represent members in transmission clusters with bootstrap values of 85% and mean genetic distance of 0.015-nucleotide substitution per site. Sequences with drug resistance mutation are highlighted with grey. The clusters correlate with the demographic information shown in table 4 in a clockwise phase (Cluster 1 through 12).