Abstract
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 g/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/L 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 g/kg were well tolerated. CD4 increases of predominantly naive and central memory T cells were brisk (averaging 323 cells/L 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 g/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.
| Original language | English |
|---|---|
| Pages (from-to) | 291-300 |
| Number of pages | 10 |
| Journal | Clinical Infectious Diseases |
| Volume | 55 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 15 2012 |
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ASJC Scopus subject areas
- Infectious Diseases
- Microbiology (medical)
Cite this
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. / Lévy, Y.; Sereti, I.; Tambussi, G.; Routy, J. P.; Lelièvre, J. D.; Delfraissy, J. F.; Molina, J. M.; Fischl, Margaret A; 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.
In: Clinical Infectious Diseases, Vol. 55, No. 2, 15.07.2012, p. 291-300.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy
T2 - Results of a phase I/IIa randomized, placebo-controlled, multicenter study
AU - Lévy, Y.
AU - Sereti, I.
AU - Tambussi, G.
AU - Routy, J. P.
AU - Lelièvre, J. D.
AU - Delfraissy, J. F.
AU - Molina, J. M.
AU - Fischl, Margaret A
AU - Goujard, C.
AU - Rodriguez, B.
AU - Rouzioux, C.
AU - Avettand-Fenoël, V.
AU - Croughs, T.
AU - Beq, S.
AU - Morre, M.
AU - Poulin, J. F.
AU - Sekaly, R. P.
AU - Thiebaut, R.
AU - Lederman, M. M.
PY - 2012/7/15
Y1 - 2012/7/15
N2 - 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 g/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/L 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 g/kg were well tolerated. CD4 increases of predominantly naive and central memory T cells were brisk (averaging 323 cells/L 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 g/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.
AB - 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 g/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/L 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 g/kg were well tolerated. CD4 increases of predominantly naive and central memory T cells were brisk (averaging 323 cells/L 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 g/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.
UR - http://www.scopus.com/inward/record.url?scp=84864125153&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864125153&partnerID=8YFLogxK
U2 - 10.1093/cid/cis383
DO - 10.1093/cid/cis383
M3 - Article
C2 - 22550117
AN - SCOPUS:84864125153
VL - 55
SP - 291
EP - 300
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 2
ER -