Effect of chemokine receptor gene polymorphisms on the response to potent antiretroviral therapy.
| Autor: | O'Brien TR; Viral Epidemiology Branch, National Cancer Institute, Bethesda, Maryland, USA. obrient@exchange.nih.gov, McDermott DH, Ioannidis JP, Carrington M, Murphy PM, Havlir DV, Richman DD |
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| Jazyk: | angličtina |
| Zdroj: | AIDS (London, England) [AIDS] 2000 May 05; Vol. 14 (7), pp. 821-6. |
| DOI: | 10.1097/00002030-200005050-00008 |
| Abstrakt: | Background: Both 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-delta32 heterozygotes is more favorable and that for CCR5 promoter allele 59029A homozygotes is less favorable. Methods: HIV-1-infected adults with a CD4+ lymphocyte count > or = 200 cells x 10(6)/l and a plasma HIV RNA level > or = 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-delta32, CCR5 59029A/G, CCR2-641) was performed. We examined whether the time to first HIV RNA < 200 copies/ml, frequency of viral suppression failure (HIV RNA > or = 200 copies/ml between weeks 16 and 28 of therapy), or reduction from the pre-treatment HIV RNA level differed by genotype. Results: Time 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. Conclusion: Polymorphisms in chemokine receptor genes may explain some of the heterogeneity in sustaining viral suppression observed among patients receiving potent antiretroviral therapy. |
| Databáze: | MEDLINE |
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