HIV‐infected viremic long‐term non‐progressors and controllers display different immunological mechanisms for preserved CD4+cell counts

Purpose Most HIV‐infected patients develop immunodeficiency without treatment. However, Long‐Term Non Progressors (LTNP) and Viremic Controllers (VC) maintain normal CD4 counts and do not progress in the absence of treatment. While VC are able to control viral replication LTNP are not. Thus, lack of viral replication cannot explain non‐progression in LTNP. Therefore we hypothesized that the immunological mechanism responsible for preserved CD4 counts in LTNP is different from that in VC. Methods 69 treatment naïve HIV‐infected patients were included in a cross‐sectional study. A total of 14 LTNP (viral load, VL>5000 copies/ml, CD4+ cell count>350 cells/ul, infected>10 years), 30 VC (VL350 cells/ul), and 25 progressors (PR) (VL>5.000 copies/ml, CD4 count>350 cells/ul) were included. Immune activation (CD4+ and CD8+cells co‐expressing CD38+HLA‐DR+), apoptosis (CD8+CD28‐CD95+), Th17 cells (CD4+CD161+), and regulatory T cells (Tregs, CD4+CD25+CD127lowFoxP3+) were evaluated using flow cytometry. For statistics Kruskal‐Wallis test followed by Mann‐Whitney U test were used. Data are given as medians. Summary of results LTNP had higher frequency of activated CD4+ and CD8+cells compared to VC (3.4% vs. 1.6%, P=0.007, 21.7% vs. 12.0%, P=0.051) and similar levels to PR (4.2%, 22.4%, P>0.05). Likewise, LTNP had higher frequency of apoptotic cells compared to VC (63.7% vs. 48.6%, P=0.0408) and similar levels to PR (63.8%, P>0.05). Interestingly, borderline significant trends towards lower Th17/Treg ratio in LTNP compared to VC were found (3.8 vs. 5.5, P=0.068) while ratios in LTNP and PR were similar (4.0, P>0.05). Conclusion LTNP displayed high levels of immune activation, apoptotic cells and reduced Th17/Treg ratio compared to VC, while LTNP were similar to PR. Thus, the immunological mechanism responsible for preserved CD4 counts in LTNP is still unclear but seems to be different from that in VC.