Background:  The use of HAART in the developed world has led to a dramatic decline in the incidence of HIV-associated dementia (HAD) and a shift toward milder forms of impairment, which collectively are called HIV-associated neurocognitive disorders (HAND). While neuropsychological definitions have been updated, there is an independent need for surrogate markers that would permit the identification of individuals at risk for the development of HAND. Host genetics contribute to HIV resistance, susceptibility, or to disease progression. CCL3L1 chemokine gene copy number below the ethnic group average has been reported to increase risk for HIV infection and the development of key AIDS-defining illnesses. The aim of this study was to determine whether CCL3L1 copy number in self-defined ethnic groups could differentiate individuals with different types of HAND.

Methods:  For this study the NorthEast AIDS Dementia (NEAD) Cohort, which is composed of patients with advanced disease from 4 participating sites, was used. In addition, DNA samples from the National NeuroAIDS Tissue Consortium (NNTC) were also analyzed. Protocols were approved by Institutional Review Boards and performed after obtaining patient consent. CCL3L1 copy number was determined in triplicate on 270 subjects using quantitative polymerase chain reaction. The relative quantitation method based on a standard curve generated with DNA from A431 cells that have a diploid CCL3L1 copy number was used. Data were analyzed using repeated measures (to account for triplets), analysis of variances with significance defined as p <0.05.

Results:  Significant differences in CCL3L1 copy number (mean [standard deviation]) between African Americans 2.7 (1.25) and Caucasians 1.45 (0.74), p <0.001 and between Hispanics 2.95 (1.26) and Caucasians, p = 0.002, were found highlighting ethnic group differences in this gene. However, there were no differences in CCL3L1 copy number across neurocognitive groups (un-impaired, minor cognitive motor disorder or HAD). Power analyses suggest that an increase in sample size would not permit detection of clinically significant differences. Among Hispanics there was a trend (not significant) toward lower copy number with increasing HAND severity that was not observed with African Americans or Caucasians. It was also notable that the mean CCL3L1 copy number in African Americans in the NEAD cohort was significantly lower than the reported ethnic group mean of 4 copies.

Conclusions:  These results suggest that CCL3L1 copy number cannot serve as a predictive marker for identifying patients at risk for developing specific HAND subtypes.