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 dosage 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.(ABSTRACT TRUNCATED AT 400 WORDS)