Co-Receptor Tropism Determined by Genotypic Assay in HIV-1 Circulating in Cuba

Abstract

Introduction: R5-tropic viruses predominated at the time of initial HIV-1 infection and a switch to X4-tropic occurs in about 50% of patients in late-stage disease. Objective: To associate different variants of Cuban HIV-1 with the co-receptor use, and the implication for the use of co-receptor inhibitors. Methodology: Viral HIV-1 subtype was determined in 42 Cuban individuals using COMET V.2, Rega subtyping toolV.3 algorithms and phylogenetic analysis. Co-receptor tropism was predicted using the geno2pheno [co-receptor] algorithm. Additionally, all V3 loop HIV-1 Cuban sequences deposited previously at Los Alamos database were also analyzed for comparison of subtype and co-receptor tropism. Results: The most frequent subtypes detected were CRF20–23–24_BG (35.7%), subtypes B (33.3%) and CRF19_ cpx (14.3%) when pol and V3 regions were analyzed. Overall, 61.9% of the samples were R5 viruses and 14.3% were X4. Viruses CRF19_cpx were more often R5X4/X4 (5/6 samples, p=0.009) or X4 strains (3/6 samples, p=0.019). The additional analysis of 359 Cuban env sequences demonstrated that only 29.3% were X4 viruses. Interestingly, 43.6% of the CRF19_cpx were R5X4/X4 viruses, confirming the previous association (p=0.011). Characteristic amino acids in the V3 loop (V/T12, R13, Q18, V19, G22) were identified at higher frequencies in CRF19_cpx viruses than in subtype B (p<0.0001). Conclusion: CRF19_cpx is a genetic form with high proportion of X4-tropic viruses. This supports the increased pathogenicity of CRF19_cpx, potentially leading to rapid disease progression. The high frequency of X4 tropism in CRF19_cpx infected patients would imply that CCR5 antagonists could be ineffective in most of these patients.