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

作者：Lee Guinevere Q^*; Lachowski Chris; Cai Eric; Lima Viviane D; Boum Yap; Muzoora Conrad; Mocello Adrienne Rain; Hunt Peter W; Martin Jeffrey N; Bang**erg David R; Harrigan P Richard

来源：AIDS, 2016, 30(11): 1781-1788.

DOI：10.1097/QAD.0000000000001128

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

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 crosssectional 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/ml P = 0.005; D: 80 vs. 128 cells/mu l 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.

• 出版日期2016-7-17