Comparative analysis of T-cell turnover and homeostatic parameters in HIV-infected patients with discordant immune-virological responses to HAART

Objective:Inadequate CD4 cell count recovery despite full HIV RNA control occurs in 30% of HAART-treated HIV-infected patients. A better understanding of the relationship between T-cell dynamics and the HIV intracellular reservoir in HIVinfected patients failing to recover CD4 cell count following long-term HAART, is required. Methods:In a cross-sectional study T-cell turnover and homeostatic parameters featuring discordant responses were investigated in 27 immunologic non-responders (INR; CD4 count, 200 cells/ml; HIV RNA, 50 copies/ml), 15 virological nonresponders (VNR; CD4 count,350 cells/ml; HIV RNA,10 000) and 22 full responders (FR; CD4 count,500 cells/ml; HIV RNA, 50 copies/ml). Results:INR displayed significantly higher activated CD38CD8 than FR (P<0.05) and was comparable to VNR (P>0.05). As compared with VNR and FR, INR displayed the highest level of proliferating Ki67CD4 and apoptotic CD4 cells (P<0.05). VNR presented lower proliferation and apoptosis than FR and INR. INR displayed the lowest levels of naive T cells (P<0.05) and a predominant memory pattern. Despite the memory/activated/apoptotic phenotype, INR showed a statistically non-significant reduction in T-cell receptor excision circles (TREC) compared to FR (P>0.05), and substantially heightened interleukin (IL)-7 (P<0.05), while VNR showed higher naive T-cell counts and TREC. Moreover, the reservoir of infected CD4 cells was increased in INR, with a trend toward highest intracellular HIV DNA within total, naive and memory CD4 cells. Conclusions:The lack of CD4 cell count recovery in INR seems to reflect a highly activated apoptotic T-cell compartment, with elevated IL-7 and thymic impairment. High levels of intracellular HIV-DNA in INR could be strictly involved in the lack of T-cell reconstitution. Immune correlates of an ultimate direction of the response