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

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.