Background:  Interleukin-7 (IL-7) plays a critical role in T cell homeostasis. We have previously reported the results of a phase I/II study of escalating doses of r-hIL-7 in chronically HIV-infected patients. IL-7 administration was safe and led to a dose-dependent increase of CD4 T cells at final evaluation (week 12). We report here the long-term follow-up until week 48.

Methods:  Patients with 100 to 400 CD4 /mL and plasma HIV RNA <50 copies/mL for at least 6 months while on HAART were eligible. Included in the first (3 mg/kg) and second (10 mg/kg) dose level were 6 and 7 patients, respectively. Patients received 8 subcutaneous injections (3 times/week; days 1 to 16) of r-hIL-7. Clinical, biological, and virological safety parameters were monitored until week 48. HIV Gag and cytomegalovirus (CMV) -specific T cell responses were assessed by intra-cellular cytokine staining in the 10 mg/kg group.

Results:  All patients received the 8 doses and were involved in the long-term follow-up. No meaningful clinical events were noted in the long-term follow-up. In the 3 mg/kg group, HIV RNA values remain <50 copies/mL throughout the study in all patients. In the 10-mg/kg group, 3 patients experienced an increase of HIV RNA values at both weeks 12 (630, 74, and 120 copies/mL) and 24 (500, 130, and 200 copies/mL). The biologic activity data of rhIL7 (median CD4, CD8 counts, and percentage increase from baseline) are shown below. The mean percentage (SD) Gag-specific CD4⁺IL-2⁺ T cells were 0.027% (0.072) and 0.157% (0.157) at baseline and week 12 (n = 7) (p = 0.027, Wilcoxon test). Of 7 patients, 6 exhibited restored detectable Gag-specific CD4⁺IL-2⁺ responses at week 12. No significant changes in the percentage of CD4⁺ interferon-gamma (IFN-g)⁺ Gag specific cells were noted (0.07% and 0.15% at baseline and week 12; p = 0.12). No changes in CMV specific CD4⁺IL-2⁺ (0.9% and 1% at baseline and week 12) or CD4⁺IFN-g⁺ (2.3% and 1.6%) were observed.

Conclusions:  In the long term, r-hIL-7 administration significantly improves CD4 T cell counts in pts with low CD4 counts. HIV-specific CD4 responses increase significantly at week 12. The possible effect of this cytokine on HIV replication should be carefully evaluated in future studies. These results reinforce interest in the clinical use of IL-7 in the treatment of HIV infection.

* p  Friedman’s test