HIV-1 Infection in Individuals With the CCR5-&Dgr;32/&Dgr;32 Genotype: Acquisition of Syncytium-Inducing Virus at Seroconversion
作者:
Haynes Sheppard,
Connie Celum,
Nelson Michael,
Stephen O'Brien,
Michael Dean,
Mary Carrington,
Dale Dondero,
Susan Buchbinder,
期刊:
JAIDS Journal of Acquired Immune Deficiency Syndromes
(OVID Available online 2002)
卷期:
Volume 29,
issue 3
页码: 307-313
ISSN:1525-4135
年代: 2002
出版商: OVID
关键词: HIV-1;CCR5-&Dgr;32/&Dgr;32;Coreceptors;CCR5;CXCR4;SI;NSI;X4-HIV-1;CCR5 genotype;Seroconverters;Homozygous/&Dgr;32
数据来源: OVID
摘要:
Homozygosity for the 32 base-pair deletion (&Dgr;32/&Dgr;32) in the CCR5 coreceptor gene is associated with incomplete HIV-1 resistance. Six HIV-1–infected &Dgr;32/&Dgr;32 patients have been reported. We report 2 additional &Dgr;32/&Dgr;32-infected individuals, among 106 seroconverters in a vaccine preparedness study. Like the previous 6, these individuals experienced rapid CD4 decline. However, taken together, the 8 patients have neither uniformly high virus load nor rapid progression to AIDS. We obtained five virus isolates from 1 patient at 5, 6, 7, 10, and 12 months after the estimated time of infection. The earliest isolate exhibits the syncytium-inducing (SI) phenotype and exclusive use of the CXCR4 coreceptor, suggesting acquisition of HIV-1 through this coreceptor. Of the remaining 104 seroconverters, 8 were CCR5-&Dgr;32/+ and 96 were CCR5-+/+. Three CCR5-+/+seroconverters who showed the uncommon pattern of early SI virus and rapid CD4 decline had uniformly high viral load and more heterogeneous coreceptor usage. These results further support the conclusion that &Dgr;32-mediated resistance is incomplete and is associated with acquisition of exclusively-X4 variants of HIV-1. The pathogenic potential of these viruses may be different from late-stage X4 virus or early X4 virus acquired by individuals with other CCR5 genotypes.
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