CCL3L1 copy number, HIV load, and immune reconstitution in sub-Saharan Africans
1 Department of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden
2 Department of Genetics, University of Leicester, University Road, Leicester, LE1 7RH, UK
3 Department of Pharmacology, Addis Ababa University, Addis Ababa, Ethiopia
4 Unit of Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
5 Internal Medicine, Addis Ababa University, Addis Ababa, Ethiopia
6 Institution of Medicine, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden
7 Department of Internal Medicine, Muhimbili National Hospital, Dar es Salaam, Tanzania
8 Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
9 Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
10 College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, UK
BMC Infectious Diseases 2013, 13:536 doi:10.1186/1471-2334-13-536Published: 12 November 2013
The role of copy number variation of the CCL3L1 gene, encoding MIP1α, 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.
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.
We find no significant association of CCL3L1 gene copy number with HIV load in antiretroviral-naïve 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.
Our work supports a role for CCL3L1 copy number in immune reconstitution following antiretroviral therapy in HIV, and suggests that the MIP1α -CCR5 axis might be targeted to aid immune reconstitution.