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

Citation
Tr. O'Brien et al., Effect of chemokine receptor gene polymorphisms on the response to potent antiretroviral therapy, AIDS, 14(7), 2000, pp. 821-826
Citations number
24
Categorie Soggetti
Immunology
Journal title
AIDS
ISSN journal
02699370 → ACNP
Volume
14
Issue
7
Year of publication
2000
Pages
821 - 826
Database
ISI
SICI code
0269-9370(20000505)14:7<821:EOCRGP>2.0.ZU;2-E
Abstract
Background: Both the natural history of HIV infection and the response to a ntiretroviral therapy are heterogeneous. Polymorphisms in chemokine recepto r genes modulate the natural history of HIV-1 infection. In comparison with subjects with other genotypes, the prognosis for HIV-1-infected CCR5-Delta 32 heterozygotes is more favorable and that for CCR5 promoter allele 59029 A homozygotes is less favorable. Methods: HIV-1-infected adults with a CD4+ lymphocyte count greater than or equal to 200 cells x 10(6)/l and a plasma HIV RNA level greater than or eq ual to 1000 copies/ml were treated with indinavir, zidovudine and lamivudin e for 6 months. HIV RNA levels were measured at 4-week intervals. Genotypin g for chemokine receptor gene polymorphisms (CCR5-Delta 32, CCR5 59029A/G, CCR2-64l) was performed. We examined whether the time to first HIV RNA < 20 0 copies/ml, frequency of viral suppression failure (HIV RNA greater than o r equal to 200 copies/ mi 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 genotyp e. 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). Afte r 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 log(10) copies/ml com pared to 2.64 log(10) copies/ml among all other groups combined. Conclusion: Polymorphisms in chemokine receptor genes may explain some of t he heterogeneity in sustaining viral suppression observed among patients re ceiving potent antiretroviral therapy. (C) 2000 Lippincott Williams & Wilki ns.