Reports on HIV/AIDS: 1990

JANUARY 26, 1990, MMWR, Vol. 39, RR-1: [inclusive page numbers]
Toxicity
Among patients who have AIDS or symptomatic HIV infection and who are treated
with zidovudine, the most frequently reported adverse events are granulocytopenia
and anemia. Other adverse events that affect >5% of zidovudine recipients include
one or more of the followirg: headache, nausea, insomnia, myalgia, diaphoresis,
fever, malaise, anorexia, diarrhea, dyspepsia, vomiting, dyspnea, rash, and taste
abnormalities (17). Occurrences less commonly reported in the published literature
include polymyositis, peripheral neuropathy, and seizures.
Among 3,200 patients with asymptomatic HIV infection treated in NIAID protocol
#019 with placebo or with zidovudine doses of either 1,500 mg or 500 mg daily (either
300 mg or 100 mg given every 4 hours, five times daily), investigators have reported
the following toxicity after a median of 44 weeks of therapy: in the 1,500-mg/day
group, approximately 12% of the subjects developed moderate to severe hematologic
toxicity, defined as hemoglobin of <8 g/dl, granulocytes of <750/mm3, or platelets of
<50,000/mm3. In the 500-mg/day group, this toxicity occurred at a rate of about 3%,
compared with approximately 2% in the placebo group. Nausea was rarely reported
in the placebo group; however, 3%-5% of zidovudine recipients, irrespective of dose
group, experienced moderate to severe nausea. No statistically significant difference
was observed between zidovudine dose and placebo for any other moderate to
severe clinical adverse experiences (NIAID Administrative Report: "AIDS Clinical
Trials Alert," August 29, 1989).
Preliminary data from a study sponsored by the Burroughs-Wellcome Company of
health-care workers who received 200 mg of zidovudine or placebo every 4 hours for
6 weeks after occupational exposure to HIV indicate that adverse effects most
frequently consisted of nausea and vomiting. In no instance did the prescribing
physician discontinue a participant's study drug or placebo because of hematologic
or other serious toxicity; however, during the therapy period, 14 (28.6%) of 49
participants who received zidovudine had a hemoglobin concentration between 9.5
and 12 g/dl, compared with one (2.9%) of 35 participants in the placebo group. Seven
(14.3%) of the 49 participants who received zidovudine, compared with one (2.9%) of
the 35 placebo recipients, elected to discontinue therapy because of subjective,
reversible symptoms, including nausea, vomiting, fatigue, headache, myalgia, or
cough.
Several anecdotal reports of short-term toxicity among health-care workers receiving zidovudine have been received by PHS. Symptoms include fever, myalgia,
fatigue, nausea, and vomiting. Single reports have been received of severe anemia,
reversible peripheral neuropathy, and transient clinical hepatitis.
Although the risk of acute zidovudine toxicity for exposed health-care workers
cannot be determined from this limited information, data from the NIAID protocol
#019 trial and from the Burroughs-Wellcome study of exposed health-care workers
suggest that the risk of acute toxicity associated with short-term use of the drug is
lower than the risk observed during long-term therapy of symptomatic HIV-infected
individuals.
For healthy persons not infected with HIV, the risk of long-term toxicity, including
teratogenic and carcinogenic effects, related to a course of zidovudine is not known.
It is not known whether zidovudine can cause fetal harm when administered to a
pregnant woman or whether it can affect reproductive capacity (17). To assess the

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