Effect of chemokine receptor gene polymorphisms on the response to potent antiretroviral therapy
Φόρτωση...
Ημερομηνία
Συγγραφείς
O'Brien, T. R.
McDermott, D. H.
Ioannidis, J. P.
Carrington, M.
Murphy, P. M.
Havlir, D. V.
Richman, D. D.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer-reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
AIDS
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
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 +/+ inverted question mark CCR2+/+ inverted question mark 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 +/+ inverted question mark CCR2+/+ inverted question mark 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.
Περιγραφή
Λέξεις-κλειδιά
Adult, Alleles, Anti-HIV Agents/*therapeutic use, Chemokine CXCL12, Chemokines, CXC/genetics, Drug Therapy, Combination, Female, Gene Frequency, HIV Infections/*drug therapy/immunology, *HIV-1/genetics/physiology, Humans, Indinavir/therapeutic use, Lamivudine/therapeutic use, Linkage Disequilibrium, Male, Polymorphism, Genetic/*genetics, RNA, Viral/blood, Receptors, CCR2, Receptors, CCR5/genetics, Receptors, Chemokine/*genetics, Receptors, Cytokine/genetics, Reverse Transcriptase Inhibitors/therapeutic use, Treatment Outcome, Zidovudine/therapeutic use
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
http://www.ncbi.nlm.nih.gov/pubmed/10839590
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής