Effects of Recombinant Human Interleukin 7 on T-Cell Recovery and Thymic Output in HIV-Infected Patients Receiving Antiretroviral Therapy: Results of a Phase I/IIa Randomized, Placebo-Controlled, Multicenter Study

• Published in: Clinical infectious diseases Vol. 55; no. 2; pp. 291 - 300
• Main Authors: Lévy, Y., Sereti, I., Tambussi, G., Routy, J. P., Lelièvre, J. D., Delfraissy, J. F., Molina, J. M., Fischl, M., Goujard, C., Rodriguez, B., Rouzioux, C., Avettand-Fenoël, V., Croughs, T., Beq, S., Morre, M., Poulin, J. F., Sekaly, R. P., Thiebaut, R., Lederman, M. M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.07.2012
• Subjects: Anti-HIV Agents - administration & dosage; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Antiviral agents; Biological and medical sciences; Blood; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; Clinical trials; Cytokines; DNA; Dosage; Drug dosages; HIV; HIV Infections - drug therapy; HIV Infections - immunology; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunologic Factors - administration & dosage; Immunologic Factors - adverse effects; Immunopathology; Infectious diseases; Interleukin-7 - administration & dosage; Interleukin-7 - adverse effects; Interleukins; Medical sciences; Memory; Pharmacology. Drug treatments; Placebos; Placebos - administration & dosage; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; RNA; T cell antigen receptors; T cell receptors; T lymphocytes; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Immunopathology; Antiretroviral agent; Thymus gland; Multicenter study; AIDS; Immune deficiency; Infection; Interleukin 7; Chemotherapy; Treatment; Immunological investigation; Viral disease; T-Lymphocyte; Phase I trial; Antiviral
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/cis383

Background. The immune deficiency of human immunodeficiency virus (HIV) infection is not fully corrected with ARV therapy. Interleukin-7 (IL-7) can boost CD4 T-cell counts, but optimal dosing and mechanisms of cellular increases need to be defined. Methods. We performed a randomized placebo-controlled dose escalation (10, 20 and 30 μg/kg) trial of 3 weekly doses of recombinant human IL-7 (rhIL-7) in ARV-treated HIV-infected persons with CD4 T-cell counts between 101 and 400 cells/μL and plasma HIV levels <50 copies/mL. Toxicity, activity and the impact of rhIL-7 on immune reconstitution were monitored. Results. Doses of rhIL-7 up to 20 μg/kg were well tolerated. CD4 increases of predominantly naive and central memory T cells were brisk (averaging 323 cells/μL at 12 weeks) and durable (up to 1 year). Increased cell cycling and transient increased bcl-2 expression were noted. Expanded cells did not have the characteristics of regulatory or activated T cells. Transient low-level HIV viremia was seen in 6 of 26 treated patients; modest increases in total levels of intracellular HIV DNA were proportional to CD4 T-cell expansions. IL-7 seemed to increase thymic output and tended to improve the T-cell receptor (TCR) repertoire in persons with low TCR diversity. Conclusions. Three weekly doses of rhIL-7 at 20 μg/kg are well tolerated and lead to a dose-dependent CD4 T-cell increase and the broadening of TCR diversity in some subjects. These data suggest that this rhIL-7 dose could be advanced in future rhIL-7 clinical studies. Clinical Trials Registration. NCT0047732.