ZIDOVUDINE - AN UPDATE OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES, AND THERAPEUTIC EFFICACY

Zidovudine remains the mainstay in the treatment of patients infected with human immunodeficiency virus (HIV). The drug delays disease progression to acquired immunodeficiency syndrome (AIDS) and to AIDS-related complex (ARC), reduces opportunistic infections, and increases survival in patients with advanced HIV infection. There is evidence to suggest that zidovudine also delays disease progression in patients with mild symptomatic disease. Although one study has shown zidovudine to have no significant beneficial effects on survival or disease progression in patients with asymptomatic HIV infection, several other studies have shown zidovudine to delay disease progression in this patient group. Results from related ongoing studies are awaited with interest. Zidovudine reduces the incidence of AIDS dementia complex (ADC) and appears to prolong survival in these patients, and improves other neurological complications of HIV infection. The drug also appears to enhance the efficacy of interferon-alpha in patients with Kaposi's sarcoma. Although zidovudine is widely used as postexposure prophylaxis following accidental exposure to HIV, its efficacy in preventing seroconversion is unclear. Whether zidovudine prevents vertical transmission also remains to be determined. The overall efficacy of zidovudine in the treatment of children with HIV infection appears similar to that in adults despite more rapid disease progression in younger patients. Zidovudine-resistant isolates can emerge as early as after 2 months' therapy, and primary infection with zidovudine-resistant strains has been documented. Both zidovudine resistance and the syncytium-inducing HIV phenotype appear to be associated with poor clinical outcome. However, zidovudine resistance may revert on drug withdrawal or switching to an alternative therapy. Zidovudine-associated haematotoxicity may be dose-limiting. Nonhaematological adverse events associated with zidovudine therapy are generally mild and usually resolve spontaneously. Dosages of approximately 500 to 600 mg/day appear to be at least as effective as dosages of 1200 to 1500 mg/day and are better tolerated in patients with less advanced disease. However, optimal dosages are unclear. Despite beneficial effects, zidovudine monotherapy is not curative. There is evidence to suggest that the concomitant administration of zidovudine with didanosine or zalcitabine is effective in patients with HIV disease progression despite receiving zidovudine monotherapy, and there is some evidence that concomitant zidovudine plus didanosine therapy is more effective than alternating monotherapy. However, results from studies of combination therapy in asymptomatic patients, and from comparative combination therapy studies are awaited. Cotherapy with agents that augment haematopoiesis allows the continuation of therapeutic zidovudine dosages. Therefore, at present, zidovudine remains the cornerstone in the treatment of HIV infection. In the near future, however, multiple agent zidovudine-containing combination therapy is likely to be the optimal treatment strategy.