Didanosine - An updated review of its use in HIV infection

Didanosine, like zidovudine, stavudine and lamivudine, is a nucleoside anal ogue reverse transcriptase inhibitor (NRTI). In the target cell for HIV, di danosine is converted to its active moiety, dideoxyadenosine-5'-triphosphat e (ddATP), which inhibits HIV reverse transcriptase and terminates viral DN A growth. It is now well established that didanosine therapy produces beneficial effe cts on virological and immunological markers of HIV disease and improves cl inical outcome in adults or children with HIV infection. In numerous clinic al trials, pronounced and sustained decreases in plasma HIV RNA levels and increases in CD4+ cell counts occurred in previously untreated or antiretro viral therapy-experienced patients treated with didanosine in combination w ith at least 1 other antiretroviral drug: zidovudine, stavudine, lamivudine , nevirapine, nelfinavir and hydroxyurea (hydroxycarbamide) are among the d rugs that have been given in combination with didanosine. Of note, HIV RNA levels decreased to below the limits of detection in some patients receivin g triple or dual therapy with didanosine-containing regimens. In double-blind, placebo-controlled trials, triple therapy with didanosine, zidovudine and nevirapine was significantly more effective than dual thera py with various combinations of these agents in improving surrogate disease markers in treatment-naive patients and in delaying disease progression or death in treatment-experienced patients with advanced disease. Improvements in virological and immunological markers were greater with did anosine-containing triple regimens than with dual therapy car monotherapy i n comparative trials, Triple therapy with didanosine, stavudine and indinav ir showed efficacy similar to that of various other triple therapy regimens in nonblind comparative trials. Comparator regimens included combinations of stavudine, lamivudine plus indinavir, zidovudine, lamivudine plus indina vir and didanosine, stavudine and nevirapine. Combination therapy with didanosine plus hydroxyurea as dual therapy or wit h a third agent produced marked and sustained decreases in HIV RNA levels i n the plasma and in lymph nodes. Combination therapy with didanosine and zi dovudine delays disease progression and prolongs survival in patients with intermediate or advanced HN infection. In large, randomised, double-blind, clinical trials, dual therapy with didanosine plus zidovudine was significa ntly more effective than zidovudine monotherapy in preventing disease progr ession and prolonging survival in previously untreated or antiretroviral th erapy-experienced patients with intermediate or advanced HIV infection. Pan creatitis and peripheral neuropathy are serious adverse effects of didanosi ne. These effects are dose-related and usually reversible after discontinua tion of treatment. Nausea, vomiting, diarrhoea and/or abdominal pain have b een reported in patients receiving treatment with the drug. Conclusions: Didanosine is an effective and generally well tolerated drug i n previously untreated and antiretroviral therapy-experienced patients with HIV infection. Given once or twice daily, it has an important role as a co mponent of triple combination regimens for the treatment of patients with s ymptomatic or asymptomatic HIV infection.