Genetic factors that confer sensitivity to HAART in HIV-infected subjects: implication of a benefit of an earlier initiation of HAART.

EVALUATION OF: Ahuja SK, Kulkarni H, Catano G et al.: CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1-infected individuals. Nat. Med. 14(4), 413-420 (2008). It is widely accepted that the effect of highly active antiretroviral therapy (HAART) varies widely among HIV-infected individuals. Host genetic factors are thought to be linked to the sensitivity to HAART in HIV-infected individuals. Ahuja et al. attempted to identify the genes that determine the sensitivity to HAART in HIV-infected subjects. Based on the hypothesis that CD4+ depletion and the recovery process in HIV-infected subjects are under the control of specific common genetic pathways, they evaluated the associations of genetic variations, such as CCR5 genotype, CCL3L1 copy number variation and HLA alleles, with the sensitivity to HAART in two cohorts from the USA. They found that the CCL3L1-CCR5 genetic risk status, but not HLA-B*57, is apparently a good predictor of the recovery rate of CD4+ T cells during HAART. In particular, the recovery rate of CD4+ T cells during HAART has the most sensitive association with the copy number of CCL3L1. Furthermore, Ahuja et al. studied the impact of CCL3L1-CCR5 genetic risks in HIV-infected individuals initiating HAART during acute or early infection. They suggested that CCL3L1-CCR5 genetic risk status may be a useful guide in deciding whether to initiate HAART in HIV-infected subjects with a level of 350 CD4+ T cells/mm(3)or more. This study has provided a critical breakthrough in predicting the response to HAART in HIV-infected subjects.