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

J. P A Ioannidis, P. S. Rosenberg, J. J. Goedert, L. J. Ashton, T. L. Benfield, S. P. Buchbinder, R. A. Coutinho, J. Eugen-Olsen, T. Gallart, T. L. Katzenstein, L. G. Kostrikis, H. Kuipers, L. G. Louie, S. A. Mallal, Joseph Bernard Margolick, O. P. Martinez, L. Meyer, N. L. Michael, E. Operskalski, G. PantaleoG. P. Rizzardi, H. Schuitemaker, H. W. Sheppard, G. J. Stewart, I. D. Theodorou, H. Ullum, E. Vicenzi, D. Vlahov, D. Wilkinson, C. Workman, J. F. Zagury, T. R. O'Brien

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)782-795
Number of pages14
JournalAnnals of Internal Medicine
Volume135
Issue number9
StatePublished - Nov 6 2001
Externally publishedYes

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Disease Progression
Meta-Analysis
HIV-1
Acquired Immunodeficiency Syndrome
Alleles
HIV Infections
RNA
Chemokine Receptors
Homozygote
Chemokines
Case-Control Studies
Cohort Studies
Prospective Studies
Genes
Seroconversion

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ioannidis, J. P. A., Rosenberg, P. S., Goedert, J. J., Ashton, L. J., Benfield, T. L., Buchbinder, S. P., ... O'Brien, T. R. (2001). 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. Annals of Internal Medicine, 135(9), 782-795.

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. / 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, L. G.; Kuipers, H.; Louie, L. G.; Mallal, S. A.; Margolick, Joseph Bernard; 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.

In: Annals of Internal Medicine, Vol. 135, No. 9, 06.11.2001, p. 782-795.

Research output: Contribution to journalArticle

Ioannidis, JPA, Rosenberg, PS, Goedert, JJ, Ashton, LJ, Benfield, TL, Buchbinder, SP, Coutinho, RA, Eugen-Olsen, J, Gallart, T, Katzenstein, TL, Kostrikis, LG, Kuipers, H, Louie, LG, Mallal, SA, Margolick, JB, Martinez, OP, Meyer, L, Michael, NL, Operskalski, E, Pantaleo, G, Rizzardi, GP, Schuitemaker, H, Sheppard, HW, Stewart, GJ, Theodorou, ID, Ullum, H, Vicenzi, E, Vlahov, D, Wilkinson, D, Workman, C, Zagury, JF & O'Brien, TR 2001, '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', Annals of Internal Medicine, vol. 135, no. 9, pp. 782-795.
Ioannidis JPA, Rosenberg PS, Goedert JJ, Ashton LJ, Benfield TL, Buchbinder SP et al. 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. Annals of Internal Medicine. 2001 Nov 6;135(9):782-795.
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, L. G. ; Kuipers, H. ; Louie, L. G. ; Mallal, S. A. ; Margolick, Joseph Bernard ; 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. / 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. In: Annals of Internal Medicine. 2001 ; Vol. 135, No. 9. pp. 782-795.
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abstract = "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.",
author = "Ioannidis, {J. P A} and Rosenberg, {P. S.} and Goedert, {J. J.} and Ashton, {L. J.} and Benfield, {T. L.} and Buchbinder, {S. P.} and Coutinho, {R. A.} and J. Eugen-Olsen and T. Gallart and Katzenstein, {T. L.} and Kostrikis, {L. G.} and H. Kuipers and Louie, {L. G.} and Mallal, {S. A.} and Margolick, {Joseph Bernard} and Martinez, {O. P.} and L. Meyer and Michael, {N. L.} and E. Operskalski and G. Pantaleo and Rizzardi, {G. P.} and H. Schuitemaker and Sheppard, {H. W.} and Stewart, {G. J.} and Theodorou, {I. D.} and H. Ullum and E. Vicenzi and D. Vlahov and D. Wilkinson and C. Workman and Zagury, {J. F.} and O'Brien, {T. R.}",
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TY - JOUR

T1 - Effects of CCR5-Δ32, CCR2-64I, and SDF-1 3′ a alleles on HIV-1 disease progression

T2 - An international meta-analysis of individual-patient data

AU - Ioannidis, J. P A

AU - Rosenberg, P. S.

AU - Goedert, J. J.

AU - Ashton, L. J.

AU - Benfield, T. L.

AU - Buchbinder, S. P.

AU - Coutinho, R. A.

AU - Eugen-Olsen, J.

AU - Gallart, T.

AU - Katzenstein, T. L.

AU - Kostrikis, L. G.

AU - Kuipers, H.

AU - Louie, L. G.

AU - Mallal, S. A.

AU - Margolick, Joseph Bernard

AU - Martinez, O. P.

AU - Meyer, L.

AU - Michael, N. L.

AU - Operskalski, E.

AU - Pantaleo, G.

AU - Rizzardi, G. P.

AU - Schuitemaker, H.

AU - Sheppard, H. W.

AU - Stewart, G. J.

AU - Theodorou, I. D.

AU - Ullum, H.

AU - Vicenzi, E.

AU - Vlahov, D.

AU - Wilkinson, D.

AU - Workman, C.

AU - Zagury, J. F.

AU - O'Brien, T. R.

PY - 2001/11/6

Y1 - 2001/11/6

N2 - 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.

AB - 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.

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