Emergence of CXCR4-tropic HIV-1 variants followed by rapid disease progression in hemophiliac slow progressors

ObjectiveThe association between emergence of CXCR4-tropic HIV-1 variants (X4 variants) and disease progression of HIV-1 infection has been reported. However, it is not known whether the emergence of X4 variants is the cause or result of HIV-1 disease progression. We tried to answer this question.DesignHIV-1 env sequences around the V3 region were analyzed in serially stocked samples in order to determine whether X4 variants emerged before or after the fall in CD4+ T-cell count.MethodsThe study subjects were five HIV-1-infected hemophiliac slow progressors. Deep sequencing around the HIV-1 env V3 region was conducted in duplicate. Tropism was predicted by geno2pheno [coreceptor] 2.5 with cutoff value of false positive ratio at ResultsEmergence of X4 variants was noted in two of the five patients when their CD4+ T-cell counts were still high. The rate of decrease of CD4+ T-cell count or of rise of HIV-1 load accelerated significantly after the emergence of X4 variants in these two cases. Phylogenetic analysis showed that these X4 variants emerged from CCR5-tropic HIV-1 viruses with several amino acid changes in the V3 region.ConclusionsThe emergence of X4 variants preceded HIV-1 disease progression in two hemophiliac slow progressors.