A Phase I/II, Open Label Study to Evaluate the Antiviral Potential of Combination Zidovudine and 2' 3'-Dideoxyinosine (Didanosine) in Patients With Asymptomatic HIV Disease

Summary

To assess the safety and to evaluate the anti-HIV effect of low-, moderate-, and high-dose schedules of zidovudine (AZT) plus didanosine (ddI) versus ddI alone in asymptomatic HIV-infected patients. Because of the failure with long-term (more than 1 year) use of, frequency of toxicity from, and drug resistance to AZT, drug combinations need to be developed to enable lower, less toxic doses of AZT to be used and to slow or prevent the development of resistance, while providing at least the same effectiveness.

Timeline

Start

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Primary completion

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Completion

1993-11

Publications

• Background Ragni MV, Amato DA, LoFaro ML, DeGruttola V, Van Der Horst C, Eyster ME, Kessler CM, Gjerset GF, Ho M, Parenti DM, et al. Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups. Blood. 1995 May 1;85(9):2337-46.
• Background Mamtora G, Winters M, Drenkow J, Shafer R, Shen N, Tran H, Merigan T, Gingeras T. HIV-1 GeneChip and dideoxynucleotide sequence analysis of HIV-1 genomes present in plasma samples from patients of ACTG 143 study. Int Conf AIDS. 1996 Jul 7-12;11(1):221 (abstract no TuA265)
• Background Morse GD, Shelton MJ, Ho M, Bartos L, DeRemer M, Ragni M. Pharmacokinetics of zidovudine and didanosine during combination therapy. Antiviral Res. 1995 Aug;27(4):419-24. doi: 10.1016/0166-3542(95)00032-h.
• Background Kozal M, Winters M, Shafer R, Kroodsma K, Katzenstein D, Merigan T. Behavior of codon 74 and 215 pol gene mutations in 62 AZT experienced patients on ddI monotherapy. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:55
• Background Fiscus SA, DeGruttola V, Gupta P, Katzenstein DA, Meyer WA 3rd, LoFaro ML, Katzman M, Ragni MV, Reichelderfer PS, Coombs RW. Human immunodeficiency virus type 1 quantitative cell microculture as a measure of antiviral efficacy in a multicenter clinical trial. J Infect Dis. 1995 Feb;171(2):305-11. doi: 10.1093/infdis/171.2.305.
• Background Winters MA, Shafer RW, Jellinger RA, Mamtora G, Gingeras T, Merigan TC. Human immunodeficiency virus type 1 reverse transcriptase genotype and drug susceptibility changes in infected individuals receiving dideoxyinosine monotherapy for 1 to 2 years. Antimicrob Agents Chemother. 1997 Apr;41(4):757-62. doi: 10.1128/AAC.41.4.757.
• Background Shafer RW, Iversen AK, Kozal MJ, Winters MA, Katzenstein DA, Merigan TC. HIV-1 (HIV) isolates resistant to both AZT and ddI developing in patients receiving combination therapy contain unique pol gene mutations. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:137
• Background Holodniy M, Katzenstein D, Winters M, Montoya J, Shafer R, Kozal M, Ragni M, Merigan TC. Measurement of HIV virus load and genotypic resistance by gene amplification in asymptomatic subjects treated with combination therapy. J Acquir Immune Defic Syndr (1988). 1993 Apr;6(4):366-9.
• Background Shafer RW, Kozal MJ, Winters MA, Katzenstein DA, Ragni MV, Merigan TC. Combination therapy with ZDV+ddI suppresses virus load but does not prevent the emergence of HIV-1 isolates with ZDV resistance. ACTG 143 Protocol Virologists. Int Conf AIDS. 1993 Jun 6-11;9(1):68 (abstract no WS-B25-3)

Drugs

Indications