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
Open accessAbstract
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.
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In HIV-infected patients with persistently low CD4+ T-cell counts despite viral suppression, repeated cycles of recombinant human IL-7 induced a dose-dependent increase in circulating levels of both naïve and memory CD4+ and mostly naïve CD8+ T cells.
“In HIV-infected patients, with persistently low CD4+ T-cell counts despite viral suppression, repeated cycles of recombinant human IL-7 induced a dose-dependent increase in circulating levels of both naïve and memory CD4+ and mostly naïve CD8+ T cells (163).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [163]
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- 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.
- Affiliations
- Inserm (FR)
- National Institutes of Health (US)
- IRCCS Ospedale San Raffaele (IT)
- McGill University Health Centre (CA)
- Hôpital Saint-Louis (FR)
- University of Miami (US)
- Bicêtre Hospital (FR)
- University Hospitals Cleveland Medical Center (US)
- Hôpital Necker-Enfants Malades (FR)
- Corresponding author
- Lévy, Y.
- ORCID
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05-01
- Volume
- 55
- Issue
- 2
- Pages
- 291-300
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC3381639
- OpenAlex
- W2146666488
- Cited by
- 240
- References
- 34
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 13 · 2023: 11 · 2022: 12 · 2021: 18 · 2020: 16 · 2019: 15 · 2018: 15 · 2017: 11 · 2016: 26 · 2015: 22 · 2014: 23 · 2013: 29 · 2012: 9
- FWCI
- 11.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Clinical Infectious Diseases (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DP1DA028871)
- National Institute of Allergy and Infectious Diseases
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
- Keywords
- HIV infection, CD4+ T cell recovery, thymic output, antiretroviral therapy, immune reconstitution, T cell receptor repertoire, Bcl-2 expression, HIV viremia, drug safety and tolerability
- MeSH terms
- Humans, Immunologic Factors, Placebos, Recombinant Proteins, CD4-Positive T-Lymphocytes, HIV Infections, Interleukin-7, Treatment Outcome, CD4 Lymphocyte Count, Anti-HIV Agents, Antiretroviral Therapy, Highly Active
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