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. 1990 Dec;66(6):418–422. doi: 10.1136/sti.66.6.418

Failure to maintain high-dose treatment regimens during long-term use of zidovudine in patients with symptomatic human immunodeficiency virus type 1 infection.

R van Leeuwen 1, P J van den Hurk 1, G J Jöbsis 1, P A van der Wouw 1, P Reiss 1, J K Eeftinck Schattenkerk 1, S A Danner 1, J M Lange 1
PMCID: PMC1194580  PMID: 2125023

Abstract

Long-term tolerance of zidovudine treatment was retrospectively analysed in 97 patients with AIDS or AIDS-related complex. After one year of treatment 68% and after two years 87% of the patients had had at least one dose adjustment during their course of therapy. Myelotoxicity was the most common cause (58% of all cases) of dose reductions and therapy interruptions (dose adjustments). At the time of the first dose adjustment 33 patients (34%) were suffering from anaemia (Hb less than 6.0 g/dl), 20 patients (21%) from leukopenia (leukocytes less than 1.5 x 10(9], and 10 patients (10%) from thrombocytopenia (thrombocytes less than 75 x 10(9]. Fifty-six patients (57%) needed one or more blood transfusions during therapy. The median time from the start of therapy to the time of the first dose adjustment was 14 (range: 2-64) weeks in patients who had a first dose adjustment because of anaemia without co-existing leukopenia or thrombocytopenia, and 37 (range: 6-85) weeks in patients who had a first dose adjustment because of leukopenia without co-existing anaemia or thrombocytopenia (p = 0.01). Peripheral blood CD4 positive lymphocyte counts less than or equal to 100/mm3, anaemia, and CDC classification IV-C1 at the start of treatment were associated with a need for an early dose modification or blood transfusion rather than the need for dose modification per se.

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Selected References

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

  1. Dalakas M. C., Illa I., Pezeshkpour G. H., Laukaitis J. P., Cohen B., Griffin J. L. Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med. 1990 Apr 19;322(16):1098–1105. doi: 10.1056/NEJM199004193221602. [DOI] [PubMed] [Google Scholar]
  2. Dournon E., Matheron S., Rozenbaum W., Gharakhanian S., Michon C., Girard P. M., Perronne C., Salmon D., De Truchis P., Leport C. Effects of zidovudine in 365 consecutive patients with AIDS or AIDS-related complex. Lancet. 1988 Dec 3;2(8623):1297–1302. doi: 10.1016/s0140-6736(88)92903-0. [DOI] [PubMed] [Google Scholar]
  3. Fischl M. A., Richman D. D., Causey D. M., Grieco M. H., Bryson Y., Mildvan D., Laskin O. L., Groopman J. E., Volberding P. A., Schooley R. T. Prolonged zidovudine therapy in patients with AIDS and advanced AIDS-related complex. AZT Collaborative Working Group. JAMA. 1989 Nov 3;262(17):2405–2410. [PubMed] [Google Scholar]
  4. Fischl M. A., Richman D. D., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):185–191. doi: 10.1056/NEJM198707233170401. [DOI] [PubMed] [Google Scholar]
  5. Fischl M. A. State of antiretroviral therapy with zidovudine. AIDS. 1989;3 (Suppl 1):S137–S143. doi: 10.1097/00002030-198901001-00021. [DOI] [PubMed] [Google Scholar]
  6. Furman P. A., Fyfe J. A., St Clair M. H., Weinhold K., Rideout J. L., Freeman G. A., Lehrman S. N., Bolognesi D. P., Broder S., Mitsuya H. Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8333–8337. doi: 10.1073/pnas.83.21.8333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gill P. S., Rarick M., Brynes R. K., Causey D., Loureiro C., Levine A. M. Azidothymidine associated with bone marrow failure in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1987 Oct;107(4):502–505. doi: 10.7326/0003-4819-107-4-502. [DOI] [PubMed] [Google Scholar]
  8. Groopman J. E., Mitsuyasu R. T., DeLeo M. J., Oette D. H., Golde D. W. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med. 1987 Sep 3;317(10):593–598. doi: 10.1056/NEJM198709033171003. [DOI] [PubMed] [Google Scholar]
  9. Helbert M., Fletcher T., Peddle B., Harris J. R., Pinching A. J. Zidovudine-associated myopathy. Lancet. 1988 Sep 17;2(8612):689–690. doi: 10.1016/s0140-6736(88)90506-5. [DOI] [PubMed] [Google Scholar]
  10. Hymes K. B., Greene J. B., Karpatkin S. The effect of azidothymidine on HIV-related thrombocytopenia. N Engl J Med. 1988 Feb 25;318(8):516–517. doi: 10.1056/NEJM198802253180812. [DOI] [PubMed] [Google Scholar]
  11. Land S., Terloar G., McPhee D., Birch C., Doherty R., Cooper D., Gust I. Decreased in vitro susceptibility to zidovudine of HIV isolates obtained from patients with AIDS. J Infect Dis. 1990 Feb;161(2):326–329. doi: 10.1093/infdis/161.2.326. [DOI] [PubMed] [Google Scholar]
  12. Larder B. A., Darby G., Richman D. D. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science. 1989 Mar 31;243(4899):1731–1734. doi: 10.1126/science.2467383. [DOI] [PubMed] [Google Scholar]
  13. Larder B. A., Kemp S. D. Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). Science. 1989 Dec 1;246(4934):1155–1158. doi: 10.1126/science.2479983. [DOI] [PubMed] [Google Scholar]
  14. Mitsuya H., Weinhold K. J., Furman P. A., St Clair M. H., Lehrman S. N., Gallo R. C., Bolognesi D., Barry D. W., Broder S. 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096–7100. doi: 10.1073/pnas.82.20.7096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Richman D. D., Fischl M. A., Grieco M. H., Gottlieb M. S., Volberding P. A., Laskin O. L., Leedom J. M., Groopman J. E., Mildvan D., Hirsch M. S. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987 Jul 23;317(4):192–197. doi: 10.1056/NEJM198707233170402. [DOI] [PubMed] [Google Scholar]
  16. Walker R. E., Parker R. I., Kovacs J. A., Masur H., Lane H. C., Carleton S., Kirk L. E., Gralnick H. R., Fauci A. S. Anemia and erythropoiesis in patients with the acquired immunodeficiency syndrome (AIDS) and Kaposi sarcoma treated with zidovudine. Ann Intern Med. 1988 Mar;108(3):372–376. doi: 10.7326/0003-4819-108-3-372. [DOI] [PubMed] [Google Scholar]
  17. Yarchoan R., Berg G., Brouwers P., Fischl M. A., Spitzer A. R., Wichman A., Grafman J., Thomas R. V., Safai B., Brunetti A. Response of human-immunodeficiency-virus-associated neurological disease to 3'-azido-3'-deoxythymidine. Lancet. 1987 Jan 17;1(8525):132–135. doi: 10.1016/s0140-6736(87)91968-4. [DOI] [PubMed] [Google Scholar]
  18. Yarchoan R., Klecker R. W., Weinhold K. J., Markham P. D., Lyerly H. K., Durack D. T., Gelmann E., Lehrman S. N., Blum R. M., Barry D. W. Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet. 1986 Mar 15;1(8481):575–580. doi: 10.1016/s0140-6736(86)92808-4. [DOI] [PubMed] [Google Scholar]

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