Skip to main content
SpringerLink
Log in

The Clinical Use of Didanosine

  • Chapter
Antiviral Chemotherapy 4

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 394))

Abstract

Didanosine (ddI) is a purine analog which inhibits HIV-1 replication in vitro at nM concentrations and is clinically effective for treatment of HIV-1 infection in a variety of clinical situations with diverse patient populations. Didanosine was only the second licensed antiretroviral in the USA and many other countries. All currently licenced agents, including zidovudine (ZDV), zalcitabine (ddC) and stavudine (d4T), are nucleoside analogs that inhibit HIV-1 reverse transcriptase by competitively inhibiting HIV-1 reverse transcriptase to bring about termination of nascent viral DNA synthesis. 1,2

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Hirsch MS, D’Aquilla RT. Therapy for human immunodeficiency virus infection. N Engl J Med 1993; 328: 1686–95.

    Article  PubMed  CAS  Google Scholar 

  2. Mitsuya H, Broder S. Inhibition of the in vitro infectivity and cytopathic effect of human Tlymphotrophic virus type III/lymphadenoapthy-associated virus (HTLV-III/LAV) by 2,3’dideoxynucleosides. Proc Natl Acad Sci USA 1986; 83: 1911–15.

    Article  PubMed  CAS  Google Scholar 

  3. Mitsuya H, Jarrett RF, Matsukura M et al. Long-term inhibition of human T-lymphotropic virus type IIUlymphoadenopathy-associated virus (human immunodeficiency virus) DNA synthesis and RNA expression in T cells protected by 2’,3’-dideoxynucleosides in vitro. Proc Natl Acad Sci USA 1987; 84: 2033–7.

    Article  PubMed  CAS  Google Scholar 

  4. Sommadossi JP. Nucleoside Analogs: Similarities and Differences. Clinical Infectious disease 1993;Sl:S7–15.

    Google Scholar 

  5. Reichman RC, Tejani N, Lambert JL et al. Didanosine (ddI) and zidovudine (ZDV) susceptibilities of human immunodeficiency virus (HIV) isolates from long-term recipients of ddI. Antiviral Research 1993; 20: 267–7.

    Article  PubMed  CAS  Google Scholar 

  6. McLeod GX, McGrath JM, Ladd EA, Hammer SM. Didanosine and zidovudine resistance patterns in clinical isolates of human immunodeficiency virus type 1 as determined by replication endpoint concentration assay. Antimicrob Agents Chemother 1992; 36: 920–5.

    Article  PubMed  CAS  Google Scholar 

  7. Martin JL, Wilson JE, Haynes RL Furman PA. Mechanism of resistance of human immunodeficiency virus type 1 to 2’,3’-dideoxyinosine. Proc. Natl. Acad. Sci. USA 1993; 9061: 35–9.

    Google Scholar 

  8. Gao Q, Gu Z, Parniak MA, Li X Wainberg MA. In vitro selection of variants of human immunodeficiency virus type 1 resistant to 3’-azido-3’deoxythymidine and 2’-,3’-dideoxyinosine. J Virology. 1992; 66: 12–9.

    Google Scholar 

  9. Gu Z, Gao Q, Li X, Parniak MA Wainberg MA. Novel mutation in the human immunodeficiency virus type 1 reverse transcriptase gene that encodes cross-resistance to 2’-3’-dideoxyinosine and 2’3’didoxycytidine. J Virology. 1992; 66: 7128–35.

    Google Scholar 

  10. St. Clair MH, Martin JL, Tudor-Williams et al. Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science 1991; 253: 1557–9.

    Google Scholar 

  11. Eron JJ, Chow YK, Caliendo AM. mutations conferring zidovudine and didanosine resistance with different effects in vitro yield multiply resistance human immunodeficiency virus type 1 isolates in vivo. Antimicrob Agents Chemotherap 1993; 37: 1480–7.

    Article  CAS  Google Scholar 

  12. Erice A, Balfour HH. Resistance of Human Immunodeficiency Virus Type 1 to antiretroviral gents: A review. J Infect Dis 1994; 18: 149–56.

    Article  CAS  Google Scholar 

  13. Mayers DL, Japour M, Arduino JM et al. Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy. Antimicrob Agent Chemotherap. 1994: 38: 307–14.

    Article  CAS  Google Scholar 

  14. Knupp CA, Shyu WC, Dolin R et al. Pharmacokinetics of didanosine in patietns with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex. Clin Pharmacol Ther 1991; 49: 523–35.

    Article  PubMed  CAS  Google Scholar 

  15. Balis FM, Pizzo PA, Butler KM et al. Clinical pharmacology of 2’,3’-dideoxyinosine in human immunodeficiency virus-infected children. J Infect Dis 1992; 165: 99–104.

    Article  PubMed  CAS  Google Scholar 

  16. Knupp CA, Bilbrath R and Barbhaiya RH. Effect of time of food administration on the bioavailability of didanosine from a chewable tablet formulation. J Clin Pharmacol 1993; 33: 568–73.

    Article  PubMed  CAS  Google Scholar 

  17. Knupp CA. Graziano FM, Dixon RN, Barbhaiya RH. Pharmacokinetic-Interaction study of didanosine and ranitidine in patients seropositive for human immunodeficiency virus. Antimicrob Agents and Chemo 1993; 36: 2075–9.

    Article  Google Scholar 

  18. Neuzil KM. Pharmacologic therapy for human immunodeficiency virus infection: a review. Amer J Med Sci 1994; 307: 368–73.

    Article  PubMed  CAS  Google Scholar 

  19. Mueller BU, Pizzo PA, Farley M et al. Pharmacokinetic evaluation of the combination of zidovudine and didanosine in children with human immunodeficiency virus infection. J Pediatrics. 1994; 125: 142–6.

    Article  CAS  Google Scholar 

  20. Yarchoan R, Mitsuya H, Thomas RV et al. In vivo activity against HIV and favorable toxicity profile of 2’,3’-dideoxyinosine. Science 1989; 245: 412–5.

    Article  PubMed  CAS  Google Scholar 

  21. Cooley TP, Kunches LM, Saunders CA et al. Once-daily administration of 2’,3’-dideoyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. N Engl J Med 1990; 322: 1340–5.

    Article  PubMed  CAS  Google Scholar 

  22. Lambert JS, Seidlin M, Reichman RC et al. 2’,3’-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. N Eng J Med 1990; 322: 1333–9.

    Article  CAS  Google Scholar 

  23. Yarchoan R, Pluda JM, Thomas RV et al. Long-term toxicity/activity profile of 2’,3’-dideoxyinosine in AIDS or AIDS-related complex Lancet 1990; 336: 526–9.

    PubMed  CAS  Google Scholar 

  24. Lambert JS, Seidlin M, Valentine FT, Reichman RC, Dolin R. Didanosine: Long-term follow-up of patients in a phase 1 study. Clin Infect Dis 1993; 16S1:S40–5.

    Google Scholar 

  25. McLaren C, Rozencweig M, Beltangady M et al. Longitudinal analysis of responses to oral didanosine therapy following zidovudine therapy in advanced infection with human immunodeficiency virus. Clini Infect Dis 1993:16S1:S32–9.

    Google Scholar 

  26. Allan JD, Connolly KJ, Fitch h et al. Long-term follow-up of didanosine administered orally twice daily to patients with advanced human immunodeficiency virus infection and hematologic intolerance of zidovudine. Clin Infect Dis 1993; 16S1:S46–51.

    Google Scholar 

  27. Pike IM, Nicaise C. The didanosine Expanded Access Program: Safety analysis. Clin Infect Dis 1993; 16 (Sl): S63–8.

    Article  PubMed  Google Scholar 

  28. Montaner JSG, Rachlis A, Beaulieu R et al. Safety profile of didanosine among patients with advanced HIV disease who are intolerant to or deteriorate despite zidovudine therapy: Results of the Canadian open ddI treatment program. J AIDS 1994; 7: 924–30.

    CAS  Google Scholar 

  29. Kahn J, Lagakos SW, Richman DD et al. A controlled trial comparing continued zidovudine with didansosine in human immunodeficiency virus infection. N Engl J Med. 1992; 327: 581–7.

    Article  PubMed  CAS  Google Scholar 

  30. Dolin R, Amato D, Fischl MA et al. Zidovudine compared to didanosine in patients with advanced HIV-1 infection and little or no previous experience with zidovudine. Arch Intern Med (in press, 1995).

    Google Scholar 

  31. Spruance SL, Pavia AT, Peterson D et al. Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine. Ann Intern Med 1994: 120: 360–8.

    Article  PubMed  CAS  Google Scholar 

  32. Darbyshire JH, Aboulker JP. Didanosine for zidovudine-intolerant patients with HIV disease. Lancet 1992;340:1346–7_

    Google Scholar 

  33. Nelson MR, Moyle GJ, Gazzard BG. Use of didanosine in zidovudine-intolerant patients infected with Human Immunodeficiency Virus. Clini Infect Dis 1993; 16SI:S59–62.

    Google Scholar 

  34. Abrams DI, Goldman AI, Launer C et al. A comparative trial of didanosine or zalcitabine after treatment with zidovudine in patients with human immunodeficiency virus infection. N Engl J Med 1994; 330: 65762.

    Article  Google Scholar 

  35. D’Aquila RT, Johnson VA, Wells SL et al. Zidovudine resistance and human immunodeficiency virus type 1 disease progression during antiretroviral therapy. Ann Intern Med (in press, 1995).

    Google Scholar 

  36. Japour AJ, Wells S, D’Aquilla RT et al. Prevalence and clinical significance of zidovudine resistance mutations in human immunodeficiency virus isolated from patients following long-term zidovudine treatment. J Infect Dis (in press, 1995).

    Google Scholar 

  37. Yarchoan R, Lietzau JA, Nguyen BY et al. Didanosine therapy in patients with symptomatic human immunodeficiency virus infection. J Infect Dis 1994; 169: 9–17.

    Article  PubMed  CAS  Google Scholar 

  38. Collier AC, Coombs RW, Fischl MA et al. Combination therapy with zidovudine and didanosine compared with zidovudine alone in HIV-1 infection. Ann Intern Med 1993; 119: 786–93.

    Article  PubMed  CAS  Google Scholar 

  39. Holodniy M, Katzenstein D, Winters M eta 1. Measurement of HIV virus load and gneotypic resistance by gne amplification in asymptomatic subjects treated with combination therapy. J AIDS 1993: 6; 366–9.

    CAS  Google Scholar 

  40. Butler KM, Husson RN Balis FM et al. Dideoxyinosine in children with symptomatic human immunodeficiency virus infection. N Engl J Med 324: 135–44.

    Google Scholar 

  41. Clerici M, Riolides E, Butler KM. Changes in T-helper cell function in human immunodeficiency virus-infected children during didansoine therapy as a measure of antiretroviral activity. Blood 1992 80: 2196 2202.

    Google Scholar 

  42. Blanche S, Calves T, Rouzloux C et al. Randomized study of two doses of didanosine in children infected with human immunodeficiency virus. J Pediatrics 1993: 966–73.

    Google Scholar 

  43. Mueller BU, Butler KM, Tocker VL et al. Clinical and pharmacokinetic evaluation of long-term therapy with didanosine in children with HIV infection. Pediatrics 1994; 94: 724–31.

    PubMed  CAS  Google Scholar 

  44. Husson RN, Mueller BU, Farley M et al. Zidovudine and didanosine combination therapy in children with human immunodeficiency virus infection. Pediatrics 1994: 93: 316–22.

    PubMed  CAS  Google Scholar 

  45. Working group on antiretroviral therapy: national Pediatric HIV Resource Center. Antiretroviral therapy and medical management of the human immunodeficiency virus-infected hild. Pediat Infect Dis J 1993:12:513–22.

    Google Scholar 

  46. Schacter LP, Rozencweig M, Beltangady M et al. Effects of therapy with didansine on hematologic parameters in patients with advanced human immunodeficiency virus disease. Blood 1992; 80: 2969–76.

    PubMed  CAS  Google Scholar 

  47. Bozzette SA, Parker R, Hay J. A cost analysis of approved antiretrovirlastreageties in person with advanced human immunodeficicney virus disease and zidovudine intolerance. J AIDS 1994; 7: 355–62.

    CAS  Google Scholar 

Download references

Authors
  1. James Kahn
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia

    John Mills

  2. University of California San Francisco, San Francisco, USA

    Paul A. Volberding

  3. University of Washington, Seattle, Washington, USA

    Lawrence Corey

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer Science+Business Media New York

About this chapter

Cite this chapter

Kahn, J. (1996). The Clinical Use of Didanosine. In: Mills, J., Volberding, P.A., Corey, L. (eds) Antiviral Chemotherapy 4. Advances in Experimental Medicine and Biology, vol 394. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9209-6_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-9209-6_22

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9211-9

  • Online ISBN: 978-1-4757-9209-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation