CCRS TRIANGLE-CCR5 HETEROZYGOSITY - A SELECTIVE PRESSURE FOR THE SYNCYTIUM-INDUCING HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PHENOTYPE/

Mechanisms underlying the delay in dominance of syncytium-inducing (SI ) phenotype HIV-1 (human immunodeficiency virus type 1) in vivo are un known. Both random mutational events and selective pressures operative only late in the disease process have been suggested to underlie the shift from CCR5 to alternative coreceptor usage, Among the moderately advanced patients who entered AIDS Clinical Trials Group protocol 241, SI viral phenotype was more common among CCR5/Delta ccr5 heterozygote s (7/7, 100%) than among CCR5/CCR5 homozygotes (29/88, 33%; P < .001, Fisher's exact test). Other characteristics did not differ at study en try by CCR5 genotype, including median CD4 cell counts, plasma RNA lev els, and infectious HIV-I titers in circulating cells. These data indi cate that CCR5/Delta ccr5 heterozygosity, which decreases cell-surface levels of CCR5 available to serve as an HIV-1 entry coreceptor, is a selective pressure for evolution of T cell line-tropic viruses that us e an alternative coreceptor.