The CCR5Δ32 allele slows disease progression of human immunodeficiency virus-1-infected children receiving antiretroviral treatment

被引:34
作者
Barroga, CF
Raskino, C
Fangon, MC
Palumbo, PE
Baker, CJ
Englund, JA
Spector, SA
机构
[1] Univ Calif San Diego, Sch Med, Dept Pediat, Div Infect Dis, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Ctr Mol Genet, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Ctr AIDS Res, La Jolla, CA 92093 USA
[4] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA
[5] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA
[6] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
[7] Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA
[8] Univ Chicago, Childrens Hosp, Dept Pediat, Chicago, IL 60637 USA
关键词
D O I
10.1086/315704
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The role of the CCR5 Delta 32 allele in human immunodeficiency virus (HIV)-1-related disease progression was analyzed for 457 antiretroviral-naive children who had participated in the Pediatric AIDS Clinical Trials Group 152 study, which demonstrated that didanosine (ddI) or zidovudine + ddI treatments were superior to zidovudine alone. The CCR5 Delta 32 allele was detected at an overall frequency of 6.1% (28/457). At study entry, heterozygote children (wild type [wt]/Delta 32) had higher baseline median CD4(+) counts/mm(3) than wt/wt children had (1035 vs. 835 cells/mm(3); P = .043), higher mean weight-for-age Z scores (-0.15 vs. -0.84; P = .01), and a trend toward less cortical atrophy (P = .059). During antiretroviral treatment and study follow-up, there was a trend toward less disease progression and death among heterozygote children than among,wt/wt children (P = .056; relative hazard, 0.28; 95% confidence interval, 0.07-1.13) independent of the antiretroviral treatment to which they were randomized.
引用
收藏
页码:413 / 419
页数:7
相关论文
共 38 条
[1]   CC CKRS: A RANTES, MIP-1 alpha, MIP-1 beta receptor as a fusion cofactor for macrophage-tropic HIV-1 [J].
Alkhatib, G ;
Combadiere, C ;
Broder, CC ;
Feng, Y ;
Kennedy, PE ;
Murphy, PM ;
Berger, EA .
SCIENCE, 1996, 272 (5270) :1955-1958
[2]  
[Anonymous], 1994, MMWR Recomm Rep, V43, P1
[3]  
Armitage P., 2001, STAT METHODS MED RES, V4th
[4]   Distribution of CCR5Δ32 in human immunodeficiency virus-infected children and its relationship to disease course [J].
Bakshi, SS ;
Zhang, LQ ;
Ho, D ;
Than, S ;
Pahwa, SG .
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, 1998, 5 (01) :38-40
[5]  
Barroga CF, 1997, AIDS, V11, P1651
[6]   Chemokine receptors as HIV-1 coreceptors: Roles in viral entry, tropism, and disease [J].
Berger, EA ;
Murphy, PM ;
Farber, JM .
ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 :657-700
[7]   HIV-1 INFECTION OF THE DEVELOPING NERVOUS-SYSTEM - CENTRAL ROLE OF ASTROCYTES IN PATHOGENESIS [J].
BLUMBERG, BM ;
GELBARD, HA ;
EPSTEIN, LG .
VIRUS RESEARCH, 1994, 32 (02) :253-267
[8]   Impact of heterozygosity for the chemokine receptor CCR5 32-bp-deleted allele on plasma virus load and CD4 T lymphocytes in perinatally human immunodeficiency virus-infected children at 8 years of age [J].
Buseyne, F ;
Janvier, G ;
Teglas, JP ;
Ivanoff, S ;
Burgard, M ;
Bui, E ;
Mayauk, MJ ;
Blanche, S ;
Rouzioux, C ;
Rivière, Y .
JOURNAL OF INFECTIOUS DISEASES, 1998, 178 (04) :1019-1023
[9]   Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene [J].
Dean, M ;
Carrington, M ;
Winkler, C ;
Huttley, GA ;
Smith, MW ;
Allikmets, R ;
Goedert, JJ ;
Buchbinder, SP ;
Vittinghoff, E ;
Gomperts, E ;
Donfield, S ;
Vlahov, D ;
Kaslow, R ;
Saah, A ;
Rinaldo, C ;
Detels, R ;
OBrien, SJ .
SCIENCE, 1996, 273 (5283) :1856-1862
[10]   Identification of a major co-receptor for primary isolates of HIV-1 [J].
Deng, HK ;
Liu, R ;
Ellmeier, W ;
Choe, S ;
Unutmaz, D ;
Burkhart, M ;
DiMarzio, P ;
Marmon, S ;
Sutton, RE ;
Hill, CM ;
Davis, CB ;
Peiper, SC ;
Schall, TJ ;
Littman, DR ;
Landau, NR .
NATURE, 1996, 381 (6584) :661-666