Reverse Transcriptase Activity (Rta) in Lymphocyte Cultures of Aids Patients Treated With Hpa-23

Buimovici‐Klein, Elena; Ong, Kenneth R.; Lange, Michael; Englard, Arthur; McKinley, George; Reddy, Mohan M.; Grieco, Michael H.; Cooper, Louis Z.

doi:10.1089/aid.1.1986.2.279

Cited by 11 publications

(4 citation statements)

References 9 publications

(9 reference statements)

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“…As a result, and because the objective of this study was to assess the tolerance of HPA-23, an overall analysis of the antiviral activity of HPA-23 was not conducted. Nonetheless, investigators at one center have concluded from their data that HPA-23 at daily doses of 0.5 or 1.0 mg/kg reduced HIV-1-specific reverse transcriptase activity during treatment (3).…”

Section: Methodsmentioning

confidence: 99%

Clinical trial of tolerance of HPA-23 in patients with acquired immune deficiency syndrome

Moskovitz¹

1988

Antimicrob Agents Chemother

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An open-label, multicenter clinical trial assessed the tolerance of HPA-23 (ammonium-21-tungsto-9-antimoniate) in patients with acquired immune deficiency syndrome. Sixty-nine patients were sequentially assigned to receive 0.25, 0.5, 1.0, or 2.0 mg of HPA-23 per kg intravenously 5 days per week for 8 weeks. HPA-23 was fairly well tolerated at doses of 1.0 mg/kg or less; nearly 60% of patients given 2.0 mg/kg discontinued treatment. Twenty-six patients discontinued treatment because of adverse events or concurrent illness. HPA-23 produced dose-related decreases in platelet count and increases in serum glutamine oxalacetic transaminase. There were no changes in immune system function, as determined by total lymphocyte count, T4-cell count, T8-cell count, and T4/T8 ratio. The effects of HPA-23 seemed to be more closely related to the total dose than to the daily dose. No improvement in the clinical status of the patients was observed during the 8 weeks of treatment.Acquired immune deficiency syndrome (AIDS) is caused by a retrovirus, human immunodeficiency virus type 1 (HIV-1) (2, 6, 11, 13). HPA-23 (ammonium-21-tungsto-9-antimoniate) inhibits retrovirus replication by inhibiting RNA-dependent DNA polymerases and thus could be effective in the treatment of HIV-1 infections and AIDS. HPA-23 inhibits nucleic acid polymerases in vitro (1, 4, 7, 10) and has antiviral activity both in vitro (14) and in vivo (8, 9). Furthermore, HPA-23 inhibits HIV-1 reverse transcriptase in vitro (5). Preliminary observations in a limited number of AIDS patients suggest that HPA-23 inhibits HIV-1 replication (12). The goal of this study was to assess the tolerance of patients with AIDS to HPA-23.(Portions of this study were presented at the Third International Conference on Acquired Immunodeficiency Syndrome, 1-5 June 1987, Washington, D.C.) MATERIALS AND METHODSThis was an open-label, multicenter clinical trial. The Institutional Review Board at each institution approved the study protocol, and all patients gave informed consent. Patients were assigned nonrandomly to the treatment groups, and no placebo was used. patients was treated with the lowest dose of HPA-23 (0.25 mg/kg per day), and the preliminary data on adverse events in these patients were evaluated. After evaluation of the results from this group, additional groups of patients were treated with higher doses of HPA-23.Patients who had AIDS, as defined by the Centers for Disease Control (Atlanta, Ga.), and who were between 18 and 60 years old, clinically stable, and ambulatory were eligible for this clinical trial. Excluded were females of childbearing potential; patients who had hemophilia; lymphoma; visceral Kaposi's sarcoma (KS); neutropenia (leukocyte count, <1,000/mm3); thrombocytopenia (platelet count, <100,000/mm3); prolonged coagulation times (prothrombin time or partial thromboplastin time of more than 2 or 8 s longer than the control times, respectively); elevated serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase, or alkaline phospha...

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Section: Methodsmentioning

confidence: 99%

Clinical trial of tolerance of HPA-23 in patients with acquired immune deficiency syndrome

Moskovitz¹

1988

Antimicrob Agents Chemother

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“…1), and those described by Ono et al [22] revealed that HPA-23 was a more potent inhibitor of cellular DNA polymerases A and c~ when compared with the inhibition of viral reverse transcriptase [3]. Despite the high toxicity of HPA-23 with respect to cellular DNA polymerases, successful therapies were reported with the use of this drug in the treatment of patients with AIDS [8,24].…”

Section: Discussionmentioning

confidence: 99%

“…In vivo, in mice, HPA-23 prevents or ameliorates infection by Friend leukemia virus, murine sarcoma virus [13], and murine scrapie [ 14]. This drug temporarily suppressed HIV replication in three AIDS patients [24], and decreased reverse transcriptase activity in lymphocyte cultures of AIDS patients [8]. We previously described an inhibitory effect of HPA-23 in the DNA synthesis reaction catalyzed by DNA polymerase ~ and reverse transcriptase [3].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the wheat germ DNA polymerase A activity by the antiviral drug HPA-23

et al. 1993

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Wheat germ DNA polymerase A, a gamma-like enzyme, recognized efficiently natural and synthetic RNA templates, resembling a retroviral reverse transcriptase (P. Laquel et al., Biochim Biophys Acta 1048 (1990): 139-148). Ammonium-21-tungsto-9-antimoniate (HPA-23), an antiviral drug, inhibited the DNA polymerase A activities, independently of the template primers used, i.e. activated DNA or polyriboadenylic acid oligodeoxythymidylate (poly(rA)-oligo(dT)). The inhibition observed in the poly(rA)-oligo(dT)-directed DNA polymerase A activity occurred in the presence of either Mg2+ or Mn2+ as divalent cation, and also with the 2'-fluoro analogue of poly(rA) as template. HPA-23 was a non-competitive inhibitor with respect to TTP, activated DNA, poly(rA)-oligo(dT), and poly(dAfl)-oligo(dT). A preincubation study showed a reversible HPA-23 binding to DNA polymerase A, in the presence of poly(rA)-oligo(dT) as the template primer.

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“…Previous reports [8,9] having proven that HPA-23 (ammonium-2 l-tungsto-9-antimoniate) inhibits the RT activity, and inhibition test was carried out with this drug. HPA-23 was kindly provided by Dr. J.C. Chermann from The Pasteur Institute, Paris, and the reaction was performed adding different concen trations of HPA-23 to the reaction mixture.…”

Section: Inhibition Testmentioning

confidence: 99%

Virus-Like Particles Associated with Reverse Transcriptase Activity in Acute Sporadic Non-A,Non-B Hepatitis

Castillo

Carréño²,

Bartolomé³

et al. 1989

Digestion

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Reverse transcriptase activity was tested in 65 patients with non-Anon-B hepatitis, with positive results in 2 acute sporadic cases with favorable outcome. Virus-like particles were observed in ultra-thin sections of successive serum samples from one of the reverse transcriptase activity-positive patients by electron microscopy. These results suggest that some non-Anon-B hepatitis types could be related to a virus-like agent associated with a reverse transcriptase activity.

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Reverse Transcriptase Activity (Rta) in Lymphocyte Cultures of Aids Patients Treated With Hpa-23

Cited by 11 publications

References 9 publications

Clinical trial of tolerance of HPA-23 in patients with acquired immune deficiency syndrome

Clinical trial of tolerance of HPA-23 in patients with acquired immune deficiency syndrome

Inhibition of the wheat germ DNA polymerase A activity by the antiviral drug HPA-23

Virus-Like Particles Associated with Reverse Transcriptase Activity in Acute Sporadic Non-A,Non-B Hepatitis

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