Effect of chemokine receptor gene polymorphisms on the response to potent antiretroviral therapy

BackgroundBoth the natural history of HIV infection and the response to antiretroviral therapy are heterogeneous. Polymorphisms in chemokine receptor genes modulate the natural history of HIV-1 infection. In comparison with subjects with other genotypes, the prognosis for HIV-1-infected CCR5-Δ32 heterozygotes is more favorable and that for CCR5 promoter allele 59029A homozygotes is less favorable. MethodsHIV-1-infected adults with a CD4+ lymphocyte count ⩾ 200 cells × 106/l and a plasma HIV RNA level ⩾ 1000 copies/ml were treated with indinavir, zidovudine and lamivudine for 6 months. HIV RNA levels were measured at 4-week intervals. Genotyping for chemokine receptor gene polymorphisms (CCR5-Δ32, CCR5 59029A/G, CCR2-64I) was performed. We examined whether the time to first HIV RNA < 200 copies/ml, frequency of viral suppression failure (HIV RNA ⩾ 200 copies/ml between weeks 16 and 28 of therapy), or reduction from the pre-treatment HIV RNA level differed by genotype. ResultsTime to first HIV RNA < 200 copies/ml was not predicted by genotype. Among 272 Caucasian patients, viral suppression failure was more common among patients with the CCR5 +/+ | CCR2+/+ | CCR5-59029 A/A genotype (28%) than among all other subjects combined (relative risk, 2.0;P = 0.06). After 24 weeks of therapy, genotype groups differed in the reduction of the HIV RNA level from baseline (P = 0.02); patients with the CCR5 +/+ | CCR2+/+ | CCR5-59029 A/A genotype had a mean reduction of 2.12 log10 copies/ml compared to 2.64 log10 copies/ml among all other groups combined. ConclusionPolymorphisms in chemokine receptor genes may explain some of the heterogeneity in sustaining viral suppression observed among patients receiving potent antiretroviral therapy.