Chemokine receptor genotype and response to interleukin-2 therapy in HIV-1-infected individuals

Interleukin-2 therapy is an immune-based treatment for HIV-1-infected individuals with declining CD4+ T cell counts. Intravenous IL-2 produces an elevation of circulating CD4+ T cells, but with a varying degree of effectiveness in individual patients. IL-2 is also known to increase the expression of chemokine receptors, coreceptors for HIV-1. Allelic variation in chemokine receptor genes can markedly affect the course of HIV disease; consequently, we analyzed CCR5 and CCR2B genotypes among a cohort of HIV-1-infected individuals that received IL-2 therapy. DNA was extracted from treated individuals and genotyping was performed using PCR followed by allele-specific detection or cleavage of the amplified product. Samples from 47 trial participants (25 CIV-IL-2 group; 22 placebo group) were analyzed for CCR5 and CCR2B genotype. We report that CCR5 Δ32 heterozygous individuals had a greater CD4+ T cell response to continuous intravenous IL-2 (CIV-IL-2) treatment than those homozygous for the wild-type allele (median = 427 vs 237 cells/mm3; P = 0.03). This study highlights the importance of interactions between IL-2 and CCR5; at the clinical level, it argues for assessment of chemokine receptor genotype in IL-2 and perhaps other immune-based therapy trials.