Background:  Patients who develop drug resistance ug resistance experience slower CD4 cell decline than untreated individuals. Factors such as, interleukin-7 receptor (IL-7Ra), T-cell activation, and replication capacity might influence this different response, independently of viremia. In this case control study, expression of IL-7Ra and activation markers on both CD4 and CD8 subsets and viral replication capacity were compared between patients with wild type and drug resistance ug resistant variants.

Methods:  We included in this study, 45 patients with genotypically confirmed drug resistance (n = 24) or wild type (n = 21) variants. Expression of interleukin (IL) -7Ra (CD127) and activation markers (CD38/HLA-DR) was assessed on both CD4 and CD8 T-cell subsets (naive, central memory, pre-terminal and terminal effector memory cells) using 8-color flow cytometry. Differences between groups were determined using the unpaired nonparametric Mann-Whitney U test. Correlations were estimated using Spearman’s test.

Results: Viral loads were similar in drug resistance and wild type patients (3.68 vs 3.72 log₁₀ copies/mL, p = 0.67). The number of major protease (PR) and reverse transcriptase (RT) mutations was 8 (range 1 to 16). Compared to wild type, drug-resist patients had a reduced replication capacity (71.8 vs 45.4%, p = 0.005). Overall, no differences in CD4 or CD8 T-cell subsets expressing IL-7Ra or activation markers were seen between drug resistance and wild type patients. However, expression of IL-7Ra was significantly reduced in drug resistance patients within CD4 terminal effector memory cell subset (41.3±5.6% vs 25.6±4.5%, p = 0.03) compared to wild type patients. Further analysis in drug resistance group showed that the presence of M184V mutation or total number of major PI and RT mutations (> or £10) had no effect on the expression of IL-7Ra or activation markers on either CD4 or CD8 T-cell subsets. A strong negative correlation was observed between CD4 or CD8 T-cell subsets expressing IL-7Ra and activation markers in patients regardless of wild type or drug resistance variant (r = –0.57; p = 0.003).

Conclusions:  Level of cell activation and IL-7Ra expression on both CD4 and CD8 cell subsets were influenced by viral load, but not by wild type or drug resistance variants. The type, the total number, and the presence of compensatory drug-resistance mutations might explain the absence of difference for cell activation and IL-7Ra expression.