Association of highly active antiretroviral therapy failure with chemokine receptor 5 wild type

OBJECTIVES: Approximately 10% of HIV-infected patients fail to respond properly to highly active antiretroviral therapy (HAART). Among other factors, genetic variants of chemokine receptors have been shown to modify the course and outcome of HIV infection. Our objective was to investigate whether a failure of virological response is associated with polymorphisms of the chemokine receptors or cofactors. METHODS: A total of 256 HIV-infected patients receiving HAART and 221 healthy controls were analysed for the chemokine receptor 5 (CCR5)-Delta32-bp, stromal derived factor 1 (SDF1)-3'A and chemokine receptor 2 (CCR2)-64I polymorphisms. Treatment failure was defined as failure to lower the viral load below 50 HIV-1 RNA copies/mL within the first year of treatment despite good adherence. Genomic DNA was extracted from peripheral blood lymphocytes (PBL) and amplified by polymerase chain reaction (PCR). RESULTS: Successful treatment was associated with heterozygosity for the CCR5-Delta32-bp variant found in 24 of 184 responders (13%) vs. one of 72 nonresponders (1.4%; P=0.004). Eighty-four of 184 responders (45.7%) vs. 25 of 72 nonresponders (34.7%) were heterozygous for the SDF1-3'A allele (P=0.073). The CCR2-64I polymorphism was rare in both groups: 4.9% in responders vs. 1.4% in nonresponders (P=0.175). The odds ratio for successful treatment was 4.7 for individuals who tested positive for at least one variant allele of the three polymorphisms. Comparison of genotype frequencies between HIV-infected and healthy individuals showed highly significant differences (P<0.001). CONCLUSIONS: Chemokine receptor polymorphisms have a modifying effect on the virological response to HAART. Multivariate analysis demonstrated that heterozygosity for the CCR5-Delta32-bp variant is an independent prognostic factor for treatment outcome.