Prevalence and clinical impacts of HIV-1 intersubtype recombinants in Uganda revealed by near-full-genome population and deep sequencing approaches

Guinevere Q. Lee, David R. Bangsberg, Theresa Mo, Chris Lachowski, Chanson J. Brumme, Wendy Zhang, Viviane D. Lima, Yap Boum, Bosco Bwana Mwebesa, Conrad Muzoora, Iren Andia, Yona Mbalibulha, Annet Kembabazi, Ryan Carroll, Mark J. Siedner, Jessica E. Haberer, A. Rain Mocello, Simone H. Kigozi, Peter W. Hunt, Jeffrey N. MartinP. Richard Harrigan

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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 languageEnglish (US)
Pages (from-to)2345-2354
Number of pages10
Issue number17
StatePublished - Nov 13 2017


  • 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


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