Effects of CCR5 - delta-32 Heterozygosity on the HIV-1 Reservoir

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Investigator: Steven G. Deeks, MD
Sponsor: Blood Systems Research Institute

Location(s): United States

Description

Previous studies on the CCR5 delta-32 mutation are based on the hypothesis that CCR5 delta-32 heterozygotes harbor a smaller, less functional, and less durable HIV-1 latent reservoir than homozygous wildtype individuals with similar infection and treatment histories. The eradication of the HIV-1 reservoir resulting in the cure of the Berlin Patient in 2009 and the sustained reduction of the HIV-1 reservoir to undetectable levels in two infected individuals in Boston in 2012 by allogeneic hematopoietic stem cell transplant (HSCT) has renewed interest in novel HIV eradication strategies.Although many factors contributed to these remarkable outcomes, it is noteworthy that all three individuals were heterozygous for the CCR5Δ32 mutation at baseline. This common genetic feature of the three individuals provides evidence that predisposition to HIV eradication may be linked to lower CCR5 cell surface expression. Given the central role of CCR5 expression in enabling HIV entry and hence replication, we hypothesized that CCR5 expression would be an important correlate of the size and characteristic of the HIV-1 reservoir.