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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Jan 1;90(1):25–29. doi: 10.1073/pnas.90.1.25

Quantitation of zidovudine-resistant human immunodeficiency virus type 1 in the blood of treated and untreated patients.

H Mohri 1, M K Singh 1, W T Ching 1, D D Ho 1
PMCID: PMC45592  PMID: 7678340

Abstract

A nonselective ex vivo assay was used to directly detect and quantify zidovudine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) in the blood of treated and untreated patients. In contrast to previous reports, drug-resistant virus was detected in peripheral blood mononuclear cells of a few of the patients who had never received AZT. The AZT resistance of HIV-1 isolates from one untreated individual was confirmed by further susceptibility studies in vitro and by the finding of a characteristic mutation (Lys-->Arg at codon 70) in the reverse transcriptase. In patients who were clinically stable while on AZT, HIV-1 titers in plasma and mononuclear cells were generally low but resistant viruses already predominated. In those individuals who were deteriorating despite AZT administration, high levels of viremia were observed, and the resistance phenotype was nearly universal. These findings serve to emphasize the magnitude of the AZT-resistance problem in patients on drug treatment.

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Selected References

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  1. Boucher C. A., Tersmette M., Lange J. M., Kellam P., de Goede R. E., Mulder J. W., Darby G., Goudsmit J., Larder B. A. Zidovudine sensitivity of human immunodeficiency viruses from high-risk, symptom-free individuals during therapy. Lancet. 1990 Sep 8;336(8715):585–590. doi: 10.1016/0140-6736(90)93391-2. [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. Ho D. D., Moudgil T., Alam M. Quantitation of human immunodeficiency virus type 1 in the blood of infected persons. N Engl J Med. 1989 Dec 14;321(24):1621–1625. doi: 10.1056/NEJM198912143212401. [DOI] [PubMed] [Google Scholar]
  4. Jacobo-Molina A., Arnold E. HIV reverse transcriptase structure-function relationships. Biochemistry. 1991 Jul 2;30(26):6351–6356. doi: 10.1021/bi00240a001. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Larder B. A., Kellam P., Kemp S. D. Zidovudine resistance predicted by direct detection of mutations in DNA from HIV-infected lymphocytes. AIDS. 1991 Feb;5(2):137–144. doi: 10.1097/00002030-199102000-00002. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Parris D. S., Harrington J. E. Herpes simplex virus variants restraint to high concentrations of acyclovir exist in clinical isolates. Antimicrob Agents Chemother. 1982 Jul;22(1):71–77. doi: 10.1128/aac.22.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Richman D. D., Grimes J. M., Lagakos S. W. Effect of stage of disease and drug dose on zidovudine susceptibilities of isolates of human immunodeficiency virus. J Acquir Immune Defic Syndr. 1990;3(8):743–746. [PubMed] [Google Scholar]
  14. Saag M. S., Hahn B. H., Gibbons J., Li Y., Parks E. S., Parks W. P., Shaw G. M. Extensive variation of human immunodeficiency virus type-1 in vivo. Nature. 1988 Aug 4;334(6181):440–444. doi: 10.1038/334440a0. [DOI] [PubMed] [Google Scholar]
  15. 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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