on Activation, Normally T Cell–Expressed and –Secreted) Neutralization of CC Chemokine Receptor 5–Using, Non–Syncytium-Inducing Virus Variants in the Course of Human Immunodeficiency Virus Type 1 Infection

In approximately half of human immunodeficiency virus (HIV) type 1–infected individuals, the development of CXC chemokine receptor 4–using, syncytium-inducing (SI) virus variants precedes a rapid progression to acquired immunodeficiency syndrome (AIDS). In other individuals, only CC chemokine receptor 5–using (R5), non-SI (NSI) virus variants are present throughout infection. These individuals may be either long-term survivors (LTSs) or rapid progressors. The basis for this variable disease progression in individuals with only R5 virus variants is not yet fully understood. In this study, the b-chemokine sensitivity of biological HIV-1 clones isolated from 13 individuals who harbored only R5, NSI virus variants (7 LTSs and 6 progressors) was investigated. We found a statistically significant decrease in sensitivity of virus variants to RANTES (regulated on activation, normally T cell–expressed and –secreted) neutralization during the course of progressive in-fection, but not during follow-up of LTSs. Our data suggest that a role exists for RANTES neutralization sensitivity of HIV-1 in AIDS pathogenesis. For entry of human immunodeficiency virus (HIV) type 1 into a target cell, a coreceptor is necessary, in addition to the principal receptor CD4. The 2 major coreceptors for HIV-1 are CCR5 and CXCR4 [1, 2]. I