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 Delta 32 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/mm(3); 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.
Clegg
Alison
A
Department of Immunology, Westmead Hospital, New South Wales 2145, Australia.
Williamson
Peter
P
Biti
Robyn
R
Cooper
David
D
Emery
Sean
S
Carr
Andrew
A
Stewart
Graeme
G
D000293:Adolescent; D000328:Adult; D000483:Alleles; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage*; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000187:drug effects / Q000235:genetics*; D019707:Receptors, Chemokine / Q000187:drug effects / Q000235:genetics*; D016896:Treatment Outcome
C515334:CCR2 protein, human; D007376:Interleukin-2; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine