AEGiS-14IAC: Causes of mortality in hiv-infected patients heterozygous for the ccr5 delta32 mutation.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Causes of mortality in hiv-infected patients heterozygous for the ccr5 delta32 mutation.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10059)

Cone LA, Gade-Andavoul R, Espinosa G
Eisenhower Med Ctr, Rancho Mirage, CA, United States

BACKGROUND: An homogeneous Δ32 deletion of the CCR5 co-receptor for HIV-1entrance into the CD4+ lymphocyte and macrophages results in nearly universal resistance to HIV-1 infection, while the heterozygous mutant becomes infected but often is a long-term non-progressor and manifests higher CD4 cell counts and lower HIV-1viral loads. Nevertheless, the CCR5 mutant gene does not continuously provide protection from AIDS-related death.

METHODS: We studied 109 HIV-1 infected patients from 1999-2001 for the CCR5 Δ32 mutation. Twenty-four (22%) tested positive for the mutation, and were ethnically all of Western Euopean origin. Causes of mortality were analysed in both groups.

RESULTS: Seven patients (29%) of those carrying the CCR5 mutation died while 15 (18%) of those with wild-type CCR5 expired during the study period. Three (43%) heterozygotes died of wasting and opportunistic infections compared to 8 (50%) in the wild-type group, while death due to neoplasms occurred in 2 (29%) of the former and in 1 (6%) in the latter group. End-stage liver disease due to chronic hepatitis B or C resulted in the death of 6 (38%) with wild-type CCR5 and in none of those with the CCR5 mutation. Finally, cardiovascular disease caused death in 2(29%) of those with the CCR5 mutation and of 1 (6%) of those without the mutation.

CONCLUSIONS: Those HIV-1 infected individuals with the CCR5 Δ32 mutation appear to succumb more often to neoplsms and letal cardiovascular events, while those with the wild- type die more frequently of end-stage liver disease due to hepatitis B or C. Death due to wasting and opportunistic infections appears similar in both groups.

Keywords: AEGIS, HIV Infections, Receptors, CCR5, AIDS Dementia Complex, HIV-1, HIV Seropositivity, Acquired Immunodeficiency Syndrome, CD4 Lymphocyte Count, Heterozygote, Mutation, CD4-Positive T-Lymphocytes, Macrophages, Greece, Human, mortality, pathogenicity, genetics

020707
A10059