Effectiveness

ddI (didanosine, Videx / VidexEC) is a common component of anti-HIV drug combinations. It should be taken with at least two other anti-HIV drugs to suppress HIV to low levels.

Approval of ddI was based on the results of four non-randomised studies into ddI taken alone. In all four studies, patients taking ddI alone showed greater increases in CD4 cell counts than patients from historical studies receiving no HIV treatment.1 2 3 4 This led to the drug’s approval in October 1991, being the second antiretroviral drug to be licensed, after AZT (zidovudine, Retrovir).

Further studies compared ddI monotherapy to AZT monotherapy, and the effects of switching from AZT to ddI monotherapy on disease outcomes. In general, these found that AZT and ddI were of similar efficacy in terms of disease progression and survival in patients with little prior AZT experience.5 6

Switching from AZT to ddI after at least four months’ treatment was also found to be beneficial, resulting in less disease progression and death than remaining on AZT monotherapy, even in patients with substantial resistance to AZT before switching.7 8 9 10 11 12 13 14 ddI was also found to be beneficial in patients who were intolerant to AZT.15 16 17

Later studies of ddI examined the effects of adding the drug to AZT monotherapy, in patients with and without experience of taking AZT. These trials, including Delta, ACTG 175, NuCombo and BW 34,225-02, found that the combination of AZT and ddI was associated with better survival and less disease progression than AZT taken alone, particularly in patients who had not taken AZT before.18 19 20 21 22 This was related to greater decreases in viral load and increases in CD4 cell counts in the patients taking AZT and ddI.23 24 25 26

Several studies have found that adding hydroxycarbamide (Hydrea), previously known as hydroxyurea, to ddI-containing regimens increases the drug’s antiviral effects.27 However, hydroxycarbamide can dampen down the CD4 cell count rise and cause significant side-effects.

ddI reaches high levels in semen, where it may have anti-HIV activity.28

References

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  2. Drusano GL et al. Relationship between dideoxyinosine exposure, CD4 counts, and p24 antigen levels in human immunodeficiency virus infection: a phase I trial. Ann Intern Med 116: 562-566, 1992
  3. Lambert JS et al. 2'-3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex: a phase I trial. N Engl J Med 322: 1333-1340, 1990
  4. Nguyen BY et al. Five-year follow-up of a phase I study of didanosine in patients with advanced human immunodeficiency virus infection. J Infect Dis 171: 1180-1189, 1995
  5. Dolin R et al. Zidovudine compared to didanosine in patients with advanced HIV-1 infection and little or no previous experience with zidovudine. Arch Intern Med 155: 961-974, 1995
  6. Floridia M et al. A randomized trial (ISS 902) of didanosine versus zidovudine in previously untreated patients with mildly symptomatic human immunodeficiency virus infection. J Infect Dis 175: 255-264, 1997
  7. Kahn JO et al. A controlled trial comparing continued zidovudine with didanosine in human immunodeficiency virus infection. N Engl J Med 327: 581-587, 1992
  8. d'Aquila RT et al. Zidovudine resistance and HIV-1 disease progression during antiretroviral therapy. Ann Intern Med 122: 401-408, 1995
  9. Raboud JM et al. Meta-analysis of five randomized controlled trials comparing continuation of zidovudine versus switching to didanosine in HIV-infected individuals. Antivir Ther 2: 237-247, 1997
  10. Gatell JM et al. Switching from zidovudine to didanosine in patients with symptomatic HIV infection and disease progression. ddI Iberian Study Group. J Acquir Immune Defic Syndr Hum Retrovirol 12: 249-258, 1996
  11. Spruance SL et al. Didanosine compared with continuation of zidovudine in HIV-infected patients with signs of clinical deterioration while receiving zidovudine. Ann Intern Med 120: 360-368, 1994
  12. Montaner JSG et al. Didanosine compared with continued zidovudine therapy for HIV-infected patients with 200 to 500 CD4 cells/mm³. double-blind, randomized, controlled trial. Canadian HIV Trials Network Protocol 002 Study Group. Ann Intern Med 123: 561-571, 1995
  13. Bach MC. Clinical response to dideoxyinosine in patients with HIV infection resistant to zidovudine. N Engl J Med 323: 275, 1990
  14. Vella S et al. A randomized trial (ISS 901) of switching to didanosine versus continued zidovudine after the diagnosis of AIDS. J Acquir Immune Defic Syndr Hum Retrovirol 12: 426-469, 1996
  15. Abrams DI et al. A comparative trial of didanosine or zalcitabine after treatment with zidovudine in patients with human immunodeficiency virus infection. N Engl J Med 330: 657-662, 1994
  16. Alpha International Coordinating Committee. The Alpha trial: European / Australian randomized double-blind trial of two doses of didanosine in zidovudine-intolerant patients with symptomatic HIV disease. AIDS 10: 867-880, 1996
  17. Jablonowski H et al. A dose comparison study of didanosine in patients with very advanced HIV infection who are intolerant to or clinically deteriorate on zidovudine. AIDS 9: 463-469, 1995
  18. Delta Coordinating Committee Delta: a randomised double-blind placebo-controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals. Lancet 348: 283-291, 1996
  19. Hammer S et al. A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 - 500 per cubic millimeter. AIDS Clinical Trials Group Study 175 Study Team. N Engl J Med 335: 1081-1090, 1996
  20. Saravoltz LD et al. Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. N Engl J Med 335: 1099-1106, 1996
  21. Schooley RT et al. Virologic and immunologic benefits of initial combination therapy with zidovudine and zalcitabine or didanosine compared with zidovudine monotherapy. J Infect Dis 173: 1354-1366, 1996
  22. Ragni MV et al. Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and non-hemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. Blood 85: 2337-2346, 1995
  23. Brun-Vezinet F et al. HIV-1 viral load, phenotype, and resistance in a subset of drug-naive participants from the Delta trial. Delta Virology Working Group and Coordinating Committee. Lancet 350: 983-990, 1997
  24. Katzenstein DA et al. The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. N Engl J Med 335: 1091-1098, 1996
  25. Mayers D et al. Viral burden measurements in CPCRA 007. Eleventh International Conference on AIDS, Vancouver, abstract Th.B.911, 1996
  26. Collier AC et al. Combination therapy with zidovudine and didanosine compared with zidovudine alone in HIV-1 infection. Ann Intern Med 119: 786-793, 1993
  27. Lopez M et al. Enhanced HIV-specific immune responses in chronically HIV-infected patients receiving didanosine plus hydroxyurea. AIDS 18: 1251-1261, 2004
  28. Cruciani M et al. Penetration of didanosine in semen of HIV-1-infected men. J Antimicrob Chemother 57: 1244-1247, 2006