Non-R5-tropic HIV-1 in subtype A1 and D infections were associated with lower pretherapy CD4 + cell count but not with PI/(N)NRTI therapy outcomes in Mbarara, Uganda

Guinevere Q. Lee, Chris Lachowski, Eric Cai, Viviane D. Lima, Yap Boum, Conrad Muzoora, Adrienne Rain Mocello, Peter W. Hunt, Jeffrey N. Martin, David R. Bangsberg, P. Richard Harrigan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Previous studies suggest that infection with non-R5-tropic subtype B HIV-1, compared with R5, is associated with a more rapid decline in CD4 + cell count, but does not affect PI/(N)NRTI therapy outcome. Here, we explored clinical correlates associated with viral tropism in subtype A1 and D infections. Methods: HIV-1 subtype A1 (n = 196) and D (n = 143) pretherapy plasma samples and up to 7.5 years of posttherapy virologic and CD4 + data were collected from a cross-sectional cohort in Mbarara, Uganda. Tropism and subtype were inferred using env V3 (geno2pheno) and gp41 (RIP) Sanger sequences. For each subtype, R5 infection was compared with non-R5 in terms of: pretherapy viral load and CD4 + cell count (Mann-Whitney tests), and therapy outcomes, including time to virologic suppression, postsuppression virologic rebound, CD4 + decline and CD4 + recovery (log-rank tests). Results: A 94% of all patients in this study achieved virologic suppression within median 3 months posttherapy. In both subtypes, non-R5 infection was associated with lower pretherapy CD4 + cell count (non-R5 vs. R5; A: median 57 vs. 147 cells/μl P = 0.005; D: 80 vs. 128 cells/μl P = 0.006). Multivariable linear regression confirmed that tropism, not subtype nor the interaction between subtype and tropism, was a significant predictor of pretherapy CD4 + cell count (P < 0.0001). None of pretherapy viral load, time to virologic suppression, virologic rebound, CD4 + decline nor CD4 + recovery was significantly different (all P > 0.09). Conclusion: Regardless of HIV-1 subtype or tropism, the majority of patients in this Ugandan cohort responded to therapy, even though non-R5 infection was associated with lower pretherapy CD4 + cell count. ©

Original languageEnglish (US)
Pages (from-to)1781-1788
Number of pages8
JournalAIDS
Volume30
Issue number11
DOIs
StatePublished - Jul 17 2016

Keywords

  • Africa
  • HIV-1
  • Uganda
  • clinical outcome
  • consequence
  • non-B tropism
  • subtype A1
  • subtype D
  • virologic outcome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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