Background: Interleukin (IL) -7 is a cytokine involved in T cell homeostasis, playing a pivotal role in T cell proliferation and survival. It is increased in lymphopenic conditions, including chronic HIV infection. In cross-sectional studies, an inverse correlation has been shown with total CD4⁺ counts, suggesting that IL-7 increases in parallel to CD4 decline during the natural course of HIV infection. We have tested this hypothesis examining the evolution of IL-7 in a group of HIV⁺ patients naive for ART in which CD4 counts significantly decreased during a long period of follow-up.

Methods: Plasma IL-7 levels were measured using a high sensitive immunoassay in a cohort of 107 untreated HIV⁺ patients and in 20 age-matched HIV-seronegative healthy volunteers. In a subset of 30 drug-naive patients, longitudinal assessments were carried out in the absence of antiretrovirals. In the cross-sectional study, correlations between IL-7, CD4 counts, and plasma viremia were assessed using the Pearson correlation coefficient. In the longitudinal study, slopes for CD4 counts and IL-7 levels were calculated for each patient using a linear regression analysis.

Results: In the cross-sectional analysis, IL-7 was significantly increased in HIV⁺ patients as compared to controls (3.48±3.36 vs 0.55±0.42 pg/mL; p <0.0001), and slightly but significantly correlated with CD4 counts after adjusting for plasma HIV RNA and age (r = –0.24; p = 0.03). In the longitudinal study, the mean follow-up was 46±14 months and the mean number of IL-7 measurements per patient was 5±0.9. During this period, mean CD4 counts significantly decreased from 803±330 to 480±257 cells/mL (p <0.0001), whereas plasma HIV RNA and IL-7 levels remained fairly stable (from 3.8±0.8 to 3.9±1.0 log copies/mL, and from 2.59±2.47 to 2.44±2.04 pg/mL, respectively). The CD4 slope was negative in all patients and statistically significant in 50% of them (mean slope in this subgroup was –8.8±6.6 cells/mL/month), whereas both HIV load and IL-7 slopes were nearly zero in most patients. In 8 patients with significant CD4 slope, CD4 counts at the end of follow up were below 350 cells/mL. Only in these patients a trend for IL-7 levels to increase over time was observed (from 2.5±3.4 to 3.6±2.9 pg/mL, n.s.).

Conclusions: In patients with chronic HIV infection and high CD4 counts, plasma IL-7 levels do not increase in response to steadily CD4 declines over time. A low CD4 threshold could exist beyond which IL-7 production is up-regulated.