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 progr ession to acquired immunodeficiency syndrome (AIDS) and to AIDS-relate d complex (ARC), reduces opportunistic infections, and increases survi val in patients with advanced HIV infection. There is evidence to sugg est that zidovudine also delays disease progression in patients with m ild symptomatic disease. Although one study has shown zidovudine to ha ve no significant beneficial effects on survival or disease progressio n in patients with asymptomatic HIV infection, several other studies h ave shown zidovudine to delay disease progression in this patient grou p. Results from related ongoing studies are awaited with interest. Zid ovudine reduces the incidence of AIDS dementia complex (ADC) and appea rs to prolong survival in these patients, and improves other neurologi cal complications of HIV infection. The drug also appears to enhance t he efficacy of interferon-alpha in patients with Kaposi's sarcoma. Alt hough 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 rem ains to be determined. The overall efficacy of zidovudine in the treat ment 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, an d primary infection with zidovudine-resistant strains has been documen ted. Both zidovudine resistance and the syncytium-inducing HIV phenoty pe appear to be associated with poor clinical outcome. However, zidovu dine resistance may revert on drug withdrawal or switching to an alter native therapy. Zidovudine-associated haematotoxicity may be dose-limi ting. Nonhaematological adverse events associated with zidovudine ther apy are generally mild and usually resolve spontaneously. Dosages of a pproximately 500 to 600 mg/day appear to be at least as effective as d osages of 1200 to 1500 mg/day and are better tolerated in patients wit h 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 disea se progression despite receiving zidovudine monotherapy, and there is some evidence that concomitant zidovudine plus didanosine therapy is m ore effective than alternating monotherapy. However, results from stud ies of combination therapy in asymptomatic patients, and from comparat ive combination therapy studies are awaited. Cotherapy with agents tha t augment haematopoiesis allows the continuation of therapeutic zidovu dine dosages. Therefore, at present, zidovudine remains the cornerston e in the treatment of HIV infection. In the near future, however, mult iple agent zidovudine-containing combination therapy is likely to be t he optimal treatment strategy.