The efficacy of combined therapy of arsenic trioxide and alpha interferon in human T-cell leukemia virus type-1-infected squirrel monkeys (Saimiri sciureus).
Human T-cell lymphotropic virus type 1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) has a poor prognosis owing to its intrinsic resistance to chemotherapy. Although zidovudine (AZT) and alpha interferon (IFN-alpha) give rise to some response and improve the prognosis of ATLL, alternative therapies are needed. Arsenic trioxide (As(2)O(3)) has been shown to synergize with IFN-alpha in arresting cell growth and inducing apoptosis of ATLL cells in vitro. In this study, we evaluated the toxicity and the efficacy of this combined treatment in HTLV-1-infected squirrel monkeys (Saimiri sciureus) and HTLV-1 infected cell lines derived therefrom. We first show that treatment with As(2)O(3) and IFN-alpha can induce growth arrest in HTLV-1-transformed monkey T-cell lines in vitro. We then show that treatment of squirrel monkeys with As(2)O(3) in vivo is highly toxic at 0.9 or 0.3mg/day but not at 0.14mg/day for up to 2 weeks. Although the combination of As(2)O(3) and IFN-alpha did not affect significantly the HTLV-1 proviral load in infected monkeys, it reduced the absolute numbers of CD3(+), CD4(+) and CD8(+) cells during treatment, with a significant reduction in the total number of circulating HTLV-1 flower cells in the infected monkeys with chronic ATLL-like disease.
Laboratoire de Rétrovirologie, Institut Pasteur de la Guyane, 23, Avenue Pasteur, 97306 Cayenne, French Guiana.
Jean Michel
JM
Heraud
Frank
F
Mortreux
Fabrice
F
Merien
Hugues
H
Contamin
Renaud
R
Mahieux
Jean Francois
JF
Pouliquen
Eric
E
Wattel
Antoine
A
Gessain
Hugues
H
de Thé
Ali
A
Bazarbachi
Olivier
O
Hermine
Mirdad
M
Kazanji
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology / Q000627:therapeutic use*; D002461:Cell Line, Transformed; D004359:Drug Therapy, Combination; D015490:HTLV-I Infections / Q000188:drug therapy* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010087:Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D012453:Saimiri; D016896:Treatment Outcome
D000998:Antiviral Agents; D001152:Arsenicals; D016898:Interferon-alpha; D010087:Oxides; D000077237:Arsenic Trioxide