Early Viral Load and CD4 + T Cell Count,But Not Percentage of CCR5 + or CXCR4 + CD4 + T Cells,Are Associated with R5-to-X4 HIV Type 1 Virus Evolution

Abstract

HIV-1 infection is established by CCR5-utilizing (R5) variants, and CXCR4-utilizing (X4) variants emerge in ∼50% of infected patients. We studied the role of CCR5 and CXCR4 expression before and 1 and 5 years after seroconversion in HIV-1 disease in a prospective study of 102 seroconverters. High percentages of CCR5⁺ cells among total cells (relative hazard [RH], 2.55; 95% confidence interval [95% CI], 0.99-6.52), but not among CD45RO^-CD4⁺ and CD45RO⁺CD4⁺ cells preseroconversion and among total cells and CD45RO^-CD4⁺ cells (RH, 2.70; 95% CI, 1.06-6.92 and RH, 3.54; 95% CI, 1.27-9.90, respectively) 5 years after seroconversion were associated with more rapid progression to AIDS. One year after seroconversion, high percentages of CXCR4⁺ cells among total and CD45RO^-CD4⁺ cells were associated with delayed development of X4 variants (RH, 0.49; 95% CI, 0.20-1.21 and RH, 0.41; 95% CI, 0.17-1.02, respectively), whereas no association was observed for the percentage of CCR5⁺ cells. In a larger study population, high early serum viral RNA and low CD4⁺ T cell numbers were associated with more rapid development of X4 variants. Our results exclude target cell availability as a driving force for R5-to-X4 virus phenotype evolution.