Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data

J P 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; J B Margolick; O P Martinez; L Meyer; N L Michael; E Operskalski; G Pantaleo; G 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; International Meta-Analysis of HIV Host Genetics

Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data

J P 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, J B 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, International Meta-Analysis of HIV Host Genetics

Institut for Klinisk Medicin

263 Citationer (Scopus)

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-Delta32 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 log(10) copies/mL and -0.14 log(10) copies/mL; P < 0.05 for both). Having the CCR5-Delta32 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-Delta32 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.

Originalsprog	Engelsk
Tidsskrift	Annals of Internal Medicine
Vol/bind	135
Udgave nummer	9
Sider (fra-til)	782-95
Antal sider	14
ISSN	0003-4819
Status	Udgivet - 6 nov. 2001

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Ioannidis, J. P., 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, J. B., Martinez, O. P., Meyer, L., Michael, N. L., Operskalski, E., ... International Meta-Analysis of HIV Host Genetics (2001). Effects of CCR5-Delta32, 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), 782-95.

Ioannidis, JP, 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 & International Meta-Analysis of HIV Host Genetics 2001, 'Effects of CCR5-Delta32, 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, bind 135, nr. 9, s. 782-95.

@article{38e7c31005d24f6e970df5b2a96b01c3,

title = "Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data",

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-Delta32 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 log(10) copies/mL and -0.14 log(10) copies/mL; P < 0.05 for both). Having the CCR5-Delta32 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-Delta32 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.",

keywords = "Acquired Immunodeficiency Syndrome, Alleles, Chemokine CXCL12, Chemokines, CXC, Disease Progression, HIV Infections, HIV-1, Heterozygote, Humans, Proportional Hazards Models, RNA, Receptors, CCR2, Receptors, CCR5, Receptors, Chemokine, Regression Analysis, Journal Article, Meta-Analysis",

author = "Ioannidis, {J P} 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, {J B} 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} and {International Meta-Analysis of HIV Host Genetics}",

year = "2001",

month = nov,

day = "6",

language = "English",

volume = "135",

pages = "782--95",

journal = "Annals of Internal Medicine",

issn = "0003-4819",

publisher = "American College of Physicians",

number = "9",

}

TY - JOUR

T1 - Effects of CCR5-Delta32, 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

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, J B

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

AU - International Meta-Analysis of HIV Host Genetics

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-Delta32 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 log(10) copies/mL and -0.14 log(10) copies/mL; P < 0.05 for both). Having the CCR5-Delta32 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-Delta32 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-Delta32 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 log(10) copies/mL and -0.14 log(10) copies/mL; P < 0.05 for both). Having the CCR5-Delta32 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-Delta32 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.

KW - Acquired Immunodeficiency Syndrome

KW - Alleles

KW - Chemokine CXCL12

KW - Chemokines, CXC

KW - Disease Progression

KW - HIV Infections

KW - HIV-1

KW - Heterozygote

KW - Humans

KW - Proportional Hazards Models

KW - RNA

KW - Receptors, CCR2

KW - Receptors, CCR5

KW - Receptors, Chemokine

KW - Regression Analysis

KW - Journal Article

KW - Meta-Analysis

M3 - Journal article

C2 - 11694103

SN - 0003-4819

VL - 135

SP - 782

EP - 795

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

IS - 9

ER -

Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data

Abstract

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