Disease relevance of didanosine

• Didanosine is another inhibitor of HIV reverse transcriptase [1].
• The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity [2].
• RESULTS: After a median follow-up of 35 months, disease progression or death occurred in 62 percent of the 363 patients assigned to zidovudine plus didanosine, 63 percent of the 367 assigned to zidovudine plus zalcitabine, and 66 percent of the 372 assigned to zidovudine only (P=0.24) [3].
• 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. Investigators for the Terry Beirn Community Programs for Clinical Research on AIDS [3].
• A significantly lower risk of anemia or neutropenia was seen in patients receiving didanosine alone (P=0.036) [2].

Psychiatry related information on didanosine

• AIDS dementia complex and didanosine [4].
• The degree of zidovudine resistance (rise in concentration required for 50% inhibition) appeared lower in the triple therapy group compared with zidovudine/didanosine (P = 0.0004) [5].
• Then patients stopped pyrazinamide and ethambutol and started once-daily antiretroviral therapy (ART) with didanosine, lamivudine, ritonavir (200 mg) and saquinavir (1600 mg) (second PK study, n = 18) [6].
• Pilot Study of Didanosine in Patients with HIV Dementia [7].

High impact information on didanosine

• Combination treatment with zidovudine, didanosine, and nevirapine in infants with human immunodeficiency virus type 1 infection [8].
• The antiviral activity of azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyinosine (ddI) against HIV-1 was comparatively evaluated in PHA-stimulated PBM [9].
• HIV-1 suppression by early treatment with hydroxyurea, didanosine, and a protease inhibitor [10].
• BACKGROUND: The Delta trial showed that combination therapy (zidovudine plus didanosine and zidovudine plus zalcitabine) substantially lengthened life and reduced disease progression compared with zidovudine monotherapy [11].
• Suppression of HIV production in resting lymphocytes by combining didanosine and hydroxamate compounds [12].

Chemical compound and disease context of didanosine

• Clinical response to dideoxyinosine in patients with HIV infection resistant to zidovudine [13].
• OBJECTIVE: To investigate 1) the effects of the magnesium-aluminum antacids in didanosine tablets on dapsone absorption in healthy volunteers and 2) the effects of the antacid formulation of active didanosine tablets on dapsone pharmacokinetics in patients seropositive for human immunodeficiency virus (HIV) [14].
• The virological and immunological efficacy of the triple regimen containing nevirapine (once or twice daily), didanosine (once daily) and stavudine, in antiretroviral-naive patients infected with HIV-1, was evaluated in an open-label, prospective, non-randomized, multi-centre, 52-week study [15].
• To study the extent to which phenotypic resistance to stavudine occurs under therapy, we studied 18 pairs of human immunodeficiency virus type 1 (HIV-1) isolates from patients both prior to and following 24-48 weeks of treatment with stavudine monotherapy or stavudine in combination with either didanosine or lamivudine [16].
• Ribavirin increases didanosine exposure, which might be clinically relevant when coadministered in HIV/HCV-coinfected patients [17].

Biological context of didanosine

• Viral sensitivity studies (done in 102 patients) showed that 28% of the zidovudine group and 21% of the didanosine group had high-level in vitro resistance to zidovudine (50% inhibitory concentration greater than 0.8 microM) at baseline (P = 0.49) [18].
• In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia [19].
• In an ongoing, open-label, non-comparative study, the safety and efficacy of nevirapine/stavudine/didanosine were evaluated in 100 antiretroviral-naive adults with CD4 cell counts > or = 200 cells/mm3 and plasma HIV-1 RNA (pVL) > or = 5000 copies/ml [20].
• However, mitochondrial genome expression was only impaired in didanosine-treated adipocytes [21].
• Patients treated with didanosine showed statistically significant improvements in hemoglobin levels, white cell counts, and granulocyte and platelet numbers as compared with baseline values [22].

Anatomical context of didanosine

• Bone marrow toxicity of dideoxyinosine [23].
• In patients treated with zidovudine plus didanosine at months 1, 3 and 6, the mean decrease in plasma HIV-1 RNA was 1.40, 1.25 and 1.12 log10 and in semen 1.10, 1.41 and 1.32 log10, respectively [24].
• HIV-infected DRG cultures exposed to indinavir or didanosine showed significant neuronal atrophy, neurite retraction, and process loss, compared with controls [25].
• METHODS: Predictors of achieving and maintaining pVL suppression were examined in a randomized trial of combinations of zidovudine, nevirapine and didanosine in patients with CD4+ T cell counts of between 200 and 600 x 10(6) cells/l who were naive to antiretroviral therapy and AIDS-free at enrolment [26].
• CONCLUSIONS: This data supports the strategy that in cases of symptomatic hyperlactatemia or lactic acidosis in which the toxicity is associated with stavudine, didanosine or both, it is safe and efficacious to reintroduce NRTI that are less potent inhibitors of mitochondria [27].

Associations of didanosine with other chemical compounds

• Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. AIDS Clinical Trials Group (ACTG) Study 152 Team [2].
• A pilot study to assess the antiviral effect of a combination of didanosine plus stavudine plus nevirapine with or without hydroxyurea in the treatment of PHI is currently under way [28].
• The aim of this study (the RESCUE trial) was to verify the effect of a shift from a lamivudine-containing to a didanosine-containing regimen on viral replication in HIV-1-infected subjects who had experienced prior treatment failure [29].
• DESIGN AND METHODS: We analysed the effects of RTIs, nucleoside analogues (NRTIs: stavudine, zidovudine, didanosine and lamivudine) and non-nucleoside analogues (NNRTIs: nevirapine and efavirenz), on differentiation, mitochondrial biogenesis and gene expression in brown adipocytes [21].
• OBJECTIVE: To explore whether the PIs nelfinavir and saquinavir and the RTIs abacavir, nevirapine, delavirdine, stavudine and didanosine affect proteasome function in vitro and in vivo [30].

Gene context of didanosine

• CXCR4-using virus was present from the onset (five patients) or appeared during clinical progression in all other patients, while taking zidovudine or didanosine monotherapy [31].
• In MCAS cells, TP53 expression was increased by ddI and AZT-TP, while p21 expression was unchanged [32].
• In HEC-1 cells the expression of both TP53 and P21 was increased by ddI [32].
• A previous study indicated that the anti-retroviral agent didanosine (2',3'-dideoxyinosine, ddI) potentiated the mutagenicity of AZT in the thymidine kinase (TK) gene of cultured human TK6 lymphoblastoid cells [33].
• Frequency of Tk and Hprt lymphocyte mutants and bone marrow micronuclei in mice treated neonatally with zidovudine and didanosine [33].

Analytical, diagnostic and therapeutic context of didanosine

• A comparative trial of didanosine or zalcitabine after treatment with zidovudine in patients with human immunodeficiency virus infection. The Terry Beirn Community Programs for Clinical Research on AIDS [34].
• Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively [35].
• We treated 22 patients who were infected with HIV-1 (viral load < 100000 copies/mL and CD4 count >150 cells/microL) with hydroxychloroquine (200 mg), hydroxycarbamide (hydroxyurea) (500 mg), and didanosine (125-200 mg), taken twice daily [36].
• The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine [37].
• Didanosine was measured in plasma using radioimmunoassay [38].

References