Didanosine is a dideoxynucleoside analogue, which is phosphorylated to the active metabolite
dideoxyadenosine triphosphate (
ddATP) intracellularly. At therapeutic concentrations,
ddATP inhibits HIV replication by inhibiting
HIV reverse transcriptase.
Didanosine is established as a first-line treatment for patients with HIV disease and has recently been shown to be superior to
zidovudine monotherapy in the treatment of patients with intermediate-stage
HIV infection. In clinical practice, however, combination regimens of antiretroviral drugs are generally considered preferable to monotherapy as first-line treatment for most patients with HIV disease. Importantly, 2 large multicentre studies have demonstrated that combination
therapy with
didanosine and
zidovudine was more effective than
zidovudine monotherapy in delaying
disease progression and death in patients with intermediate or advanced HIV disease. In other comparative studies, improvements in
surrogate markers of HIV disease were generally greater in patients who received combination
therapy than in recipients of antiretroviral
drug monotherapy. Improvements in
surrogate markers were also observed in children who received
didanosine monotherapy in several clinical trials. Although the efficacy of combination antiretroviral
drug therapy has not yet been investigated extensively in children, a combination regimen of
didanosine and
zidovudine was well tolerated and achieved beneficial effects on
surrogate markers if HIV disease. In addition, preliminary findings of a larger study have shown that
disease progression was delayed in children and adolescents who received
didanosine plus
zidovudine combination
therapy compared with those receiving
zidovudine monotherapy.
Didanosine has a tolerability profile that is distinctly different from that of
zidovudine. In particular,
didanosine exhibits only minimal haematological toxicity when administered either as a single agent or in combination with
zidovudine. The most serious dose-limiting adverse effects associated with
didanosine treatment are
peripheral neuropathy and
pancreatitis. In conclusion,
didanosine monotherapy is an effective treatment of
HIV infection. However,
combination antiretroviral therapy is the optimal treatment strategy for most patients, and
didanosine is now firmly established as a component of combination antiretroviral
drug regimens for the first-line treatment of patients with HIV disease.