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HIV-1 infection in individuals with the CCR5-Delta32/Delta32 genotype: acquisition of syncytium-inducing virus at seroconversion
Source:
J Infect Dis 2002 Apr 1;185(7):990-3
Authors:
Sheppard HW, Celum C, Michael NL, O'Brien S, Dean M, Carrington M, Dondero D,
Buchbinder SP
Publication Info:
Viral and Rickettsial Disease Laboratory, California Department of Health Services,
Richmond, California 94804, USA. hsheppar@dhs.ca.gov
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Abstract:
Homozygosity for the 32 base-pair deletion (Delta32/Delta32) in the CCR5 coreceptor
gene is associated with incomplete HIV-1 resistance. Six HIV-1-infected
Delta32/Delta32 patients have been reported. We report 2 additional
Delta32/Delta32-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-Delta32/+ 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 Delta32-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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