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 Bangsberg, P. Richard Harrigan

Research output: Contribution to journalArticle

1 Citation (Scopus)

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
Externally publishedYes

Fingerprint

Uganda
CD4 Lymphocyte Count
Tropism
HIV-1
Infection
Viral Tropism
Therapeutics
Viral Load
Linear Models

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

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

In: AIDS, Vol. 30, No. 11, 17.07.2016, p. 1781-1788.

Research output: Contribution to journalArticle

Lee, GQ, Lachowski, C, Cai, E, Lima, VD, Boum, Y, Muzoora, C, Mocello, AR, Hunt, PW, Martin, JN, Bangsberg, D & Harrigan, PR 2016, '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', AIDS, vol. 30, no. 11, pp. 1781-1788. https://doi.org/10.1097/QAD.0000000000001128
Lee, Guinevere Q. ; Lachowski, Chris ; Cai, Eric ; Lima, Viviane D. ; Boum, Yap ; Muzoora, Conrad ; Mocello, Adrienne Rain ; Hunt, Peter W. ; Martin, Jeffrey N. ; Bangsberg, David ; Harrigan, P. Richard. / 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. In: AIDS. 2016 ; Vol. 30, No. 11. pp. 1781-1788.
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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. {\circledC}",
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T1 - 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

AU - Lee, Guinevere Q.

AU - Lachowski, Chris

AU - Cai, Eric

AU - Lima, Viviane D.

AU - Boum, Yap

AU - Muzoora, Conrad

AU - Mocello, Adrienne Rain

AU - Hunt, Peter W.

AU - Martin, Jeffrey N.

AU - Bangsberg, David

AU - Harrigan, P. Richard

PY - 2016/7/17

Y1 - 2016/7/17

N2 - 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. ©

AB - 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. ©

KW - Africa

KW - clinical outcome

KW - consequence

KW - HIV-1

KW - non-B tropism

KW - subtype A1

KW - subtype D

KW - Uganda

KW - virologic outcome

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