Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1994 Feb;38(2):260–267. doi: 10.1128/aac.38.2.260

Safety, activity, and pharmacokinetics of GLQ223 in patients with AIDS and AIDS-related complex.

J O Kahn 1, K J Gorelick 1, G Gatti 1, C J Arri 1, J D Lifson 1, J G Gambertoglio 1, A Bostrom 1, R Williams 1
PMCID: PMC284438  PMID: 7910722

Abstract

GLQ223 is a highly purified single-chain ribosome-inactivating protein with selective effects against a variety of cells, including macrophages infected with human immunodeficiency virus. We evaluated the safety, pharmacokinetics, and immunologic effects of multiple doses of GLQ223 in 22 patients with AIDS or AIDS-related complex; CD4+ T-cell counts were between 100 and 350/mm3. GLQ223 was administered intravenously at doses of 8, 16, 24, 36, and 50 micrograms/kg of body weight; the drug was administered by constant infusion over 3 h to achieve a concentration in serum of 50 ng/ml; this concentration is known to be associated with anti-HIV effects in vitro. All patients reported a flu-like syndrome characterized by muscle and joint aches and an increase in creatinine kinase levels; symptoms were controlled easily. For patients who received 36 and 50 micrograms/kg, target concentrations in serum were achieved and an increase in CD4+ and CD8+ T cells was sustained; this sustained increase persisted for at least 28 days after the last infusion. beta 2-Microglobulin levels increased during the infusions and then declined when the infusions ended. Repeat infusions of GLQ223 were safe and relatively well tolerated. The target concentration of GLQ223 in serum was achieved and sustained. Our results suggest that GLQ223 may have activity in treating patients with human immunodeficiency virus infection.

Full text

PDF
264

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aron G. M., Irvin J. D. Inhibition of herpes simplex virus multiplication by the pokeweed antiviral protein. Antimicrob Agents Chemother. 1980 Jun;17(6):1032–1033. doi: 10.1128/aac.17.6.1032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bass H. Z., Hardy W. D., Mitsuyasu R. T., Taylor J. M., Wang Y. X., Fischl M. A., Spector S. A., Richman D. D., Fahey J. L. The effect of zidovudine treatment on serum neopterin and beta 2-microglobulin levels in mildly symptomatic, HIV type 1 seropositive individuals. J Acquir Immune Defic Syndr. 1992;5(3):215–221. [PubMed] [Google Scholar]
  3. Byers V. S., Levin A. S., Waites L. A., Starrett B. A., Mayer R. A., Clegg J. A., Price M. R., Robins R. A., Delaney M., Baldwin R. W. A phase I/II study of trichosanthin treatment of HIV disease. AIDS. 1990 Dec;4(12):1189–1196. doi: 10.1097/00002030-199012000-00002. [DOI] [PubMed] [Google Scholar]
  4. Carrasco L. Membrane leakiness after viral infection and a new approach to the development of antiviral agents. Nature. 1978 Apr 20;272(5655):694–699. doi: 10.1038/272694a0. [DOI] [PubMed] [Google Scholar]
  5. Crowe S. M., McGrath M. S., Elbeik T., Kirihara J., Mills J. Comparative assessment of antiretrovirals in human monocyte-macrophages and lymphoid cell lines acutely and chronically infected with the human immunodeficiency virus. J Med Virol. 1989 Nov;29(3):176–180. doi: 10.1002/jmv.1890290306. [DOI] [PubMed] [Google Scholar]
  6. Fernández-Puentes C., Carrasco L. Viral infection permeabilizes mammalian cells to protein toxins. Cell. 1980 Jul;20(3):769–775. doi: 10.1016/0092-8674(80)90323-2. [DOI] [PubMed] [Google Scholar]
  7. Ferrari P., Trabaud M. A., Rommain M., Mandine E., Zalisz R., Desgranges C., Smets P. Toxicity and activity of purified trichosanthin. AIDS. 1991 Jul;5(7):865–870. doi: 10.1097/00002030-199107000-00011. [DOI] [PubMed] [Google Scholar]
  8. Gatti G., Kahn J. O., Lifson J., Williams R., Turin L., Volberding P. A., Gambertoglio J. G. Pharmacokinetics of GLQ223 in rats, monkeys, and patients with AIDS or AIDS-related complex. Antimicrob Agents Chemother. 1991 Dec;35(12):2531–2537. doi: 10.1128/aac.35.12.2531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goldstein G., Fuccello A. J., Norman D. J., Shield C. F., 3rd, Colvin R. B., Cosimi A. B. OKT3 monoclonal antibody plasma levels during therapy and the subsequent development of host antibodies to OKT3. Transplantation. 1986 Nov;42(5):507–511. doi: 10.1097/00007890-198611000-00013. [DOI] [PubMed] [Google Scholar]
  10. Irvin J. D. Pokeweed antiviral protein. Pharmacol Ther. 1983;21(3):371–387. doi: 10.1016/0163-7258(83)90061-x. [DOI] [PubMed] [Google Scholar]
  11. Jacobson M. A., Abrams D. I., Volberding P. A., Bacchetti P., Wilber J., Chaisson R. E., Crowe S., Howard W., Moss A. Serum beta 2-microglobulin decreases in patients with AIDS or ARC treated with azidothymidine. J Infect Dis. 1989 Jun;159(6):1029–1036. doi: 10.1093/infdis/159.6.1029. [DOI] [PubMed] [Google Scholar]
  12. Kahn J. O., Kaplan L. D., Gambertoglio J. G., Bredesen D., Arri C. J., Turin L., Kibort T., Williams R. L., Lifson J. D., Volberding P. A. The safety and pharmacokinetics of GLQ223 in subjects with AIDS and AIDS-related complex: a phase I study. AIDS. 1990 Dec;4(12):1197–1204. doi: 10.1097/00002030-199012000-00003. [DOI] [PubMed] [Google Scholar]
  13. Lee-Huang S., Huang P. L., Kung H. F., Li B. Q., Huang P. L., Huang P., Huang H. I., Chen H. C. TAP 29: an anti-human immunodeficiency virus protein from Trichosanthes kirilowii that is nontoxic to intact cells. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6570–6574. doi: 10.1073/pnas.88.15.6570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mayes J. T., Thistlethwaite J. R., Jr, Stuart J. K., Buckingham M. R., Stuart F. P. Reexposure to OKT3 in renal allograft recipients. Transplantation. 1988 Feb;45(2):349–353. [PubMed] [Google Scholar]
  15. McGrath M. S., Hwang K. M., Caldwell S. E., Gaston I., Luk K. C., Wu P., Ng V. L., Crowe S., Daniels J., Marsh J. GLQ223: an inhibitor of human immunodeficiency virus replication in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2844–2848. doi: 10.1073/pnas.86.8.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McGrath M. S., Santulli S., Gaston I. Effects of GLQ223 on HIV replication in human monocyte/macrophages chronically infected in vitro with HIV. AIDS Res Hum Retroviruses. 1990 Aug;6(8):1039–1043. doi: 10.1089/aid.1990.6.1039. [DOI] [PubMed] [Google Scholar]
  17. Oksenhendler E., Bierling P., Ferchal F., Clauvel J. P., Seligmann M. Zidovudine for thrombocytopenic purpura related to human immunodeficiency virus (HIV) infection. Ann Intern Med. 1989 Mar 1;110(5):365–368. doi: 10.7326/0003-4819-110-5-365. [DOI] [PubMed] [Google Scholar]
  18. Olson M. C., Ramakrishnan S., Anand R. Ribosomal inhibitory proteins from plants inhibit HIV-1 replication in acutely infected peripheral blood mononuclear cells. AIDS Res Hum Retroviruses. 1991 Dec;7(12):1025–1030. doi: 10.1089/aid.1991.7.1025. [DOI] [PubMed] [Google Scholar]
  19. Perno C. F., Yarchoan R., Cooney D. A., Hartman N. R., Gartner S., Popovic M., Hao Z., Gerrard T. L., Wilson Y. A., Johns D. G. Inhibition of human immunodeficiency virus (HIV-1/HTLV-IIIBa-L) replication in fresh and cultured human peripheral blood monocytes/macrophages by azidothymidine and related 2',3'-dideoxynucleosides. J Exp Med. 1988 Sep 1;168(3):1111–1125. doi: 10.1084/jem.168.3.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Richman D. D., Kornbluth R. S., Carson D. A. Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages. J Exp Med. 1987 Oct 1;166(4):1144–1149. doi: 10.1084/jem.166.4.1144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ussery M. A., Irvin J. D., Hardesty B. Inhibition of poliovirus replication by a plant antiviral peptide. Ann N Y Acad Sci. 1977 Mar 4;284:431–440. doi: 10.1111/j.1749-6632.1977.tb21979.x. [DOI] [PubMed] [Google Scholar]
  22. Zarling J. M., Moran P. A., Haffar O., Sias J., Richman D. D., Spina C. A., Myers D. E., Kuebelbeck V., Ledbetter J. A., Uckun F. M. Inhibition of HIV replication by pokeweed antiviral protein targeted to CD4+ cells by monoclonal antibodies. Nature. 1990 Sep 6;347(6288):92–95. doi: 10.1038/347092a0. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES