Heterozygosity for a deletion in the CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals

Abstract

Individuals who are heterozygous for the 32-base-pair deletion in the CKR-5 gene have a slower decrease in their CD4 T-cell count and a longer AIDS-free survival than individuals with the wild-type gene for up to 11 years of follow-up.

Frequency of CCR5-Δ32 deletion in human immunodeficiency virus type 1 (HIV-1) in healthy blood donors, HIV-1-exposed seronegative and HIV-1-seropositive individuals of southern Brazilian population

“…Although the heterozygosity was not related to the complete protection against HIV-1 infection (6,8), it may confer partial protection against disease progression or death in HIV-1 infected individuals (9)(10)(11)(12)(13)(14)(15)(16). Heterozygosity for the CCR5-Δ32 deletion is significantly higher in cohorts of HIV-1 infected long-term non-progressors (LTNP) compared to HIV-1 infected typical progressor individuals (9,17,18).…”

Regional variation in CCR5-Δ32 gene distribution among women from the US HIV Epidemiology Research Study (HERS)

“…3 HIV-infected individuals heterozygous for CCR5 (+/⌬32) have about a 2-year delay in progression to AIDS and slower CD4 + T cell decline compared with HIV infected individuals who do not carry the ⌬32 polymorphism. [4][5][6] We have examined the distribution of this gene in a cohort of United States (US) women known as the HIV Epidemiology Research Study (HERS). This is a prospective, multisite study conducted to define the epidemiologic, biologic, psychological, and social effects of HIV-1 infection on the health of US women and to examine the progression of HIV-1 disease.…”

Higher macrophage inflammatory protein (MIP)-1α and MIP-1β levels from CD8+T cells are associated with asymptomatic HIV-1 infection

“…The profound impact of reduced coreceptor accessibility on HIV infection in vivo is strongly supported by evidence that individuals homozygous for a mutant CCR5 allele encoding a fusion-defective molecule (⌬32) are strongly resistant to infection (26,27). Moreover, the heterozygous condition provides a limited resistance to disease progression (28,29).…”