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. 1989 Jun;33(6):920–923. doi: 10.1128/aac.33.6.920

Human immunodeficiency virus inhibition is prolonged by 3'-azido-3'-deoxythymidine alternating with 2',3'-dideoxycytidine compared with 3'-azido-3'-deoxythymidine alone.

S A Spector 1, D Ripley 1, K Hsia 1
PMCID: PMC284255  PMID: 2548440

Abstract

The inhibition of the lymphadenopathy-associated virus strain of human immunodeficiency virus (HIV) by alternating regimens of two dideoxynucleosides, 3'-azido-3'-deoxythymidine (AZT) (zidovudine) and 2',3'-dideoxycytidine (ddC), was determined in CEM cells. Cultures infected with virus for 2 h were treated with clinically achievable concentrations of AZT, ddC, or a 3-day-alternating regimen of AZT and ddC. Media were completely changed every 3 days and replaced with antiviral agent, and virus production was assayed by p24 antigen and virus-specific DNA. Cells treated with no antiviral agent exhibited breakthrough infection by day 6 in culture, whereas cells treated with 0.1, 1.0, or 3.0 microM AZT had a prolonged time to viral breakthrough. For each regimen of AZT alternating with 0.05 or 0.1 microM ddC, there was consistently prolonged HIV inhibition compared with continuous treatment with AZT alone. The viral suppression achieved with the alternating combinations required AZT as well as ddC and was superior to 3 days of treatment with ddC alternating with 3 days of no antiretroviral treatment. Levels of unintegrated HIV DNA paralleled the detection of p24 antigen, with the most prolonged inhibition of virus-specific DNA occurring with AZT alternating with ddC (compared with all regimens except continuous treatment with ddC). These data suggest that alternating regimens of AZT and ddC not only might decrease toxicity associated with the two drugs but may prove to be more efficacious than AZT alone.

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Selected References

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  1. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  4. Jackson G. G., Paul D. A., Falk L. A., Rubenis M., Despotes J. C., Mack D., Knigge M., Emeson E. E. Human immunodeficiency virus (HIV) antigenemia (p24) in the acquired immunodeficiency syndrome (AIDS) and the effect of treatment with zidovudine (AZT). Ann Intern Med. 1988 Feb;108(2):175–180. doi: 10.7326/0003-4819-108-2-175. [DOI] [PubMed] [Google Scholar]
  5. Merigan T. C., Skowron G., Bozzette S. A., Richman D., Uttamchandani R., Fischl M., Schooley R., Hirsch M., Soo W., Pettinelli C. Circulating p24 antigen levels and responses to dideoxycytidine in human immunodeficiency virus (HIV) infections. A phase I and II study. Ann Intern Med. 1989 Feb 1;110(3):189–194. doi: 10.7326/0003-4819-110-3-189. [DOI] [PubMed] [Google Scholar]
  6. Mitsuya H., Broder S. Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1911–1915. doi: 10.1073/pnas.83.6.1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Nakashima H., Matsui T., Harada S., Kobayashi N., Matsuda A., Ueda T., Yamamoto N. Inhibition of replication and cytopathic effect of human T cell lymphotropic virus type III/lymphadenopathy-associated virus by 3'-azido-3'-deoxythymidine in vitro. Antimicrob Agents Chemother. 1986 Dec;30(6):933–937. doi: 10.1128/aac.30.6.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Paul D. A., Falk L. A., Kessler H. A., Chase R. M., Blaauw B., Chudwin D. S., Landay A. L. Correlation of serum HIV antigen and antibody with clinical status in HIV-infected patients. J Med Virol. 1987 Aug;22(4):357–363. doi: 10.1002/jmv.1890220408. [DOI] [PubMed] [Google Scholar]
  9. Richman D. D., Andrews J. Results of continued monitoring of participants in the placebo-controlled trial of zidovudine for serious human immunodeficiency virus infection. Am J Med. 1988 Aug 29;85(2A):208–213. [PubMed] [Google Scholar]
  10. 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]
  11. Smith M. S., Brian E. L., Pagano J. S. Resumption of virus production after human immunodeficiency virus infection of T lymphocytes in the presence of azidothymidine. J Virol. 1987 Dec;61(12):3769–3773. doi: 10.1128/jvi.61.12.3769-3773.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Spector S. A., Spector D. H. The use of DNA probes in studies of human cytomegalovirus. Clin Chem. 1985 Sep;31(9):1514–1520. [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Yarchoan R., Perno C. F., Thomas R. V., Klecker R. W., Allain J. P., Wills R. J., McAtee N., Fischl M. A., Dubinsky R., McNeely M. C. Phase I studies of 2',3'-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT). Lancet. 1988 Jan 16;1(8577):76–81. doi: 10.1016/s0140-6736(88)90283-8. [DOI] [PubMed] [Google Scholar]

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