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

HIV-1 infection is established by CCR5-utilizing (R5) variants, and CXCR4-utilizing (X4) variants emerge in similar to50% 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