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HIV-1 Infection in Individuals With the CCR5-δ32/δ32 Genotype: Acquisition of Syncytium-Inducing Virus at Seroconversion

Sheppard, Haynes W.; Celum, Connie; Michael, Nelson L.; O'Brien, Stephen; Dean, Michael; Carrington, Mary; Dondero, Dale; Buchbinder, Susan P.
JAIDS Journal of Acquired Immune Deficiency Syndromes: March 1st, 2002
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Homozygosity for the 32 base-pair deletion (Δ32/Δ32) in the CCR5 coreceptor gene is associated with incomplete HIV-1 resistance. Six HIV-1-infected Δ32/Δ32 patients have been reported. We report 2 additional Δ32/Δ32-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-Δ32/+ 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 Δ32-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.

Address correspondence and reprint requests to Haynes W. Sheppard, Viral and Rickettsial Disease Laboratory, California Department of Health Services, 850 Marina Bay Parkway, Richmond. CA 94804, U.S.A.; e-mail: hsheppar@dhs.ca.gov

The content of this publication does not necessarily reflect the views or policies of the U. S. Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Manuscript received May 14, 2001; accepted October 29, 2001.

© 2002 Lippincott Williams & Wilkins, Inc.