Non-R5-tropic HIV-1 in Subtype A1 and D Infections Were Associated with Lower Pre-therapy CD4 Count But Not with PI/(N)NRTI Therapy Outcomes in Mbarara, Uganda

Abstract

Background: Previous studies suggest that infection with non-R5-tropic subtype B HIV-1, compared to R5, is associated with a more rapid decline in CD4 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) pre-therapy plasma samples and up to 7.5 years of post-therapy 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: Pre-therapy viral load and CD4 count (Mann-Whitney tests), and therapy outcomes including time to virologic suppression, post-suppression virologic rebound, CD4 decline and CD4 recovery (Log-rank tests). Results: 94% of all patients in this study achieved virologic suppression within median 3 months post-therapy. In both subtypes, non-R5 infection was associated with lower pre-therapy CD4 count (non-R5 versus R5; A: median 57 versus 147 cells/μL p=0.005; D: 80 versus 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 pre-therapy CD4 count (p<0.0001). None of pre-therapy 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 pre-therapy CD4 count.