Primary CXCR4 Co-receptor Use in Acute HIV Infection Leads to Rapid Disease Progression in the AE Subtype

This is a comparative study of HIV co-receptor usage in the early stages of HIV infection between two distinct patient groups, one with a low CD4 count (group 1), and the other with a high CD4 count (group 2). Group 1 progressed to a CD4 count below 200 cells/mu L within 2 y, while group 2 had a CD4 count above 500 cells/mu L within 2 y. Viral RNA was extracted from the plasma of these patients, and the C2-V5 region of the HIV-1 env genes were cloned and sequenced. The co-receptor usage was predicated based on V3 loop amino acid sequences using Geno2pheno and PSSM programs. Our results indicate that in acute HIV infection of rapid progressors (low CD4 count; group 1), the primary co-receptor usage is CXCR4, while in the high CD4 count group (group 2), the co-receptor usage is predominantly CCR5. One-year follow-up data from these patients showed no obvious change in HIV co-receptor usage in either group. Sequence analysis of patients from both study groups showed prevalence of the AE subtype, and therefore we can speculate that the CXCR4 co-receptor may be the primary HIV-1 co-receptor used in the HIV-1 AE subtype, and may be responsible for rapid HIV-1 disease progression in the MSM cohort.