CCL3L1 copy number, HIV load, and immune reconstitution in sub-Saharan Africans

Background: The role of copy number variation of the CCL3L1 gene, encoding MIP1 alpha, in contributing to the host variation in susceptibility and response to HIV infection is controversial. Here we analyse a sub-Saharan African cohort from Tanzania and Ethiopia, two countries with a high prevalence of HIV-1 and a high co-morbidity of HIV with tuberculosis. Methods: We use a form of quantitative PCR called the paralogue ratio test to determine CCL3L1 gene copy number in 1134 individuals and validate our copy number typing using array comparative genomic hybridisation and fiber-FISH. Results: We find no significant association of CCL3L1 gene copy number with HIV load in antiretroviral-naive patients prior to initiation of combination highly active anti-retroviral therapy. However, we find a significant association of low CCL3L1 gene copy number with improved immune reconstitution following initiation of highly active anti-retroviral therapy (p = 0.012), replicating a previous study. Conclusions: Our work supports a role for CCL3L1 copy number in immune reconstitution following antiretroviral therapy in HIV, and suggests that the MIP1 alpha -CCR5 axis might be targeted to aid immune reconstitution.