Abstract
Objectives: HIV-1 subtypes A1 and D cocirculate in a rural community in Mbarara, Uganda. This study examines HIV-1 intersubtype recombination in this community under a full-genome sequencing context. We aim to estimate prevalence, examine time trends, and test for clinical correlates and outcomes associated with intersubtype recombinants. Methods: Near-full-genome HIV-1 Sanger sequence data were collected from plasma samples of 504 treatment-naïve individuals, who then received protease inhibitor or nonnucleoside reverse transcriptase inhibitor-containing regimens and were monitored for up to 7.5 years. Subtypes were inferred by Los Alamos Recombinant Identification Program (RIP) 3.0 and compared with Sanger/REGA and MiSeq/RIP. 'Nonrecombinants' and 'recombinants' infections were compared in terms of pretherapy viral load, CD4 + cell count, posttherapy time to virologic suppression, virologic rebound, first CD4 + rise above baseline and sustained CD4 + recovery. Results: Prevalence of intersubtype recombinants varied depending on the genomic region examined: gag (15%), prrt (11%), int (8%), vif (10%), vpr (2%), vpu (9%), GP120 (8%), GP41 (18%), and nef (4%). Of the 200 patients with near-full-genome data, prevalence of intersubtype recombination was 46%; the most frequently observed recombinant was A1-D (25%). Sanger/REGA and MiSeq/RIP yielded generally consistent results. Phylogenetic tree revealed most recombinants did not share common ancestors. No temporal trend was observed (all P>0.1). Subsequent subtype switches were detected in 27 of 143 (19%) study participants with follow-up sequences. Nonrecombinant versus recombinants infections were not significantly different in any pre nor posttherapy clinical correlates examined (all P>0.2). Conclusion: Intersubtype recombination was highly prevalent (46%) in Uganda if the entire HIV genome was considered, but was neither associated with clinical correlates nor therapy outcomes.
Original language | English (US) |
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Pages (from-to) | 2345-2354 |
Number of pages | 10 |
Journal | AIDS |
Volume | 31 |
Issue number | 17 |
DOIs | |
State | Published - Nov 13 2017 |
Keywords
- Africa
- HIV-1
- Uganda
- clinical outcomes
- consequence
- deep sequencing
- full-genome sequencing
- non-B subtypes
- recombinants
- virologic outcomes
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases