We hypothesized that there may be a correlation between the interleukin-7 (IL-7)/IL-7 receptor (IL-7R) regulatory system and parameters of T-cell homeostasis in HIV-infected long-term nonprogressors (LTNPs) as compared with patients with disease progression. MethodsThe possibility of a correlation between T-cell homeostatic parameters and IL-7/IL-7R was investigated in 22 LTNPs (CD4 count ! 500 cells/mL for 410 years) vs. HIV-positive patients at different disease stages [12 early: CD4 count ! 400 cells/mL; 15 late (AIDS-presenters): CD4 count 150 cells/mL]. ResultsCompared with early-stage HIV-positive patients, LTNPs displayed a higher circulating IL-7 concentration (P 5 0.05), which was positively associated with higher IL-7Ra expression and a higher T-cell receptor excision circle (TREC) content specifically within CD4 cells (Po0.05). Compared with late-stage disease patients, early-stage disease patients displayed a lower IL-7 concentration (Po0.01) and higher percentages of IL-7Ra 1 CD4 and CD8 cells (P 5 0.05). IL-7 was positively correlated with the percentage of TREC 1 CD4 cells (Po0.01), which translated into a higher percentage of naïve CD4 cells in early-stage disease patients than in late-stage disease patients; however, the CD4 cells in early-stage disease patients were less enriched in recent thymic emigrants (RTEs) compared with LTNPs (Po0.05). In late-stage AIDS-developing patients, substantially increased IL-7 was correlated with a decreased percentage of IL-7Ra 1 CD4 cells (P 5 0.01), which resulted in these patients having a significantly lower percentage of naïve T cells (Po0.01) and a significantly lower content of TREC (Po0.01) than the other patients. ConclusionsThe maintenance of high CD4 cell counts in LTNPs was associated with a specific IL-7/IL-7R pattern characterized by increased IL-7 and highest IL-7Ra-expressing CD4 cells relative to other patients. Compared with patients with late-stage disease, LTNPs displayed a phenotypically naïve, less activated CD4 cell pool highly enriched in RTEs, suggesting the existence of a compensatory IL-7-mediated pathway specifically sustaining peripheral CD4 counts.

The risk of opportunistic infections and inefficient immune reconstitution in advanced naive HIV+ patients starting HAART are critical issues in the management of HIV infection. We studied the effects of IL-2 adjuvant therapy in favoring a rapid CD4 cell rescue, shortening the time frame at highest risk of HIV-related clinical events in patients with severe immune impairment. MethodsAfter 2 weeks of HAART, 73 HAART-naive patients with baseline CD4 cells <200/μL were randomized to receive IL-2+HAART (n = 33) or to continue ongoing HAART (n = 40). Three cycles of IL-2 were administered (one cycle: 3 × 106 IU QD sc at days 1-5 and 8-12), for an overall duration of 3 months. Patients were followed-up over 18 months. Patients failing to show a sustained CD4 recovery of >30% from baseline after 6 months (IL-2 non-responders, IL-2NR) received three further IL-2 cycles.

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