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

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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.

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