Effects of CCR5-Δ32, CCR2-64I, and SDF-1 3′ a alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data
| Autor: | Ioannidis, J. P. A., Rosenberg, P. S., Goedert, J. J., Ashton, L. J., Benfield, T. L., Buchbinder, S. P., Coutinho, R. A., Eugen-Olsen, J., Gallart, T., Katzenstein, T. L., Kostrikis, Leontios G., Kuipers, H., Louie, L. G., Mallal, S. A., Margolick, J. B., Martinez, O. P., Meyer, L., Michael, N. L., Operskalski, E., Pantaleo, G., Rizzardi, G. P., Schuitemaker, H., Sheppard, H. W., Stewart, G. J., Theodorou, I. D., Ullum, H., Vicenzi, E., Vlahov, D., Wilkinson, D., Workman, C., Zagury, J. -F, O'Brien, T. R. |
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| Přispěvatelé: | Kostrikis, Leontios G. [0000-0002-5340-7109] |
| Rok vydání: | 2001 |
| Předmět: |
chemokine receptor CCR5
Receptors CCR5 proportional hazards model chemokine receptor CCR2 Human immunodeficiency virus 1 HIV Infections monocyte chemoattractant protein 1 receptor genetic risk acquired immune deficiency syndrome regression analysis Human immunodeficiency virus infection Humans genetics stromal cell derived factor 1 human seroconversion Alleles Proportional Hazards Models Acquired Immunodeficiency Syndrome alpha chemokine disease course disease association article allele risk assessment chemokine receptor clinical trial major clinical study mortality heterozygote priority journal Disease Progression HIV-1 RNA Receptors Chemokine metabolism disease activity Chemokines CXC meta analysis |
| Zdroj: | Annals of Internal Medicine Ann.Intern.Med. |
| Popis: | Background: Studies relating certain chemokine and chemokine receptor gene alleles with the outcome of HIV-1 infection have yielded inconsistent results. Objective: To examine postulated associations of genetic alleles with HIV-1 disease progression. Design: Meta-analysis of individual-patient data. Setting: 19 prospective cohort studies and case-control studies from the United States, Europe, and Australia. Patients: Patients with HIV-1 infection who were of European or African descent. Measurements: Time to AIDS, death, and death after AIDS and HIV-1 RNA level at study entry or soon after seroconversion. Data were combined with fixed-effects and random-effects models. Results: Both the CCR5-Δ32 and CCR2-64I alleles were associated with a decreased risk for progression to AIDS (relative hazard among seroconverters, 0.74 and 0.76, respectively P = 0.01 for both), a decreased risk for death (relative hazard among seroconverters, 0.64 and 0.74 P < 0.05 for both), and lower HIV-1 RNA levels after seroconversion (difference, -0.18 log10 copies/mL and -0.14 log10 copies/mL P < 0.05 for both). Having the CCR5-Δ32 or CCR2-64I allele had no clear protective effect on the risk for death after development of AIDS. The results were consistent between seroconverters and seroprevalent patients. In contrast, SDF-1 3′A homozygotes showed no decreased risk for AIDS (relative hazard for seroconverters and seroprevalent patients, 0.99 and 1.03, respectively), death (relative hazard, 0.97 and 1.00), or death after development of AIDS (relative hazard, 0.81 and 0.97 P < 0.5 for all). Conclusions: The CCR5-Δ32 and CCR2-64I alleles had a strong protective effect on progression of HIV-1 infection, but SDF-1 3′A homozygosity carried no such protection. 135 782 795 Cited By :238 |
| Databáze: | OpenAIRE |
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