This is an un-blinded, voluntary, open-label toxicity trial assessing combination therapy of zidovudine plus lamivudine and, when indicated, indinavir as agents for post-exposure chemoprophylaxis for health care workers (HCWs) sustaining occupational exposures to human immunodeficiency virus (HIV). Indinavir may be added when the exposure is especially severe or when drug-resistant HIV is suspected. This is an amendment of the protocol, which previously assessed the toxicity of zidovudine or zidovudine plus didanosine. The two secondary purposes of this study are (1) to assess the effect of combination chemoprophylaxis on the temporal sequence of the appearance of markers of HIV infection should it occur in a HCW taking chemoprophylaxis, and (2) to describe the epidemiology of exposures to HIV for which combination chemoprophylaxis is elected in institutions participating in this study. Zidovudine, lamivudine, and indinavir, if indicated, are initiated as soon as possible for the exposed HCW, but no longer than 72 hours post- exposure. Zidovudine dosage is 200 mg 3x/day for 28 days; lamivudine dosage is 150 mg 2x/day for 28 days. If indicated, indinavir can be added as a third agent at anytime up to 72 hours after the first dose of zidovudine/ lamivudine; the indinavir dose is 800 mg 3x/day, and the total duration of prophylaxis remains at 28 days. Exposed HCWs are followed for a minimum of 12 months. After the baseline enrollment visit, follow-up visits occur at 2, 4, and 6 weeks, and 3, 6, and 12 months. Individuals are assessed for drug toxicity as well as for early signs of HIV infection. Since July 1996, 10 HCWs have elected to take combination chemoprophylaxis (eight took three drugs, two took only two drugs). Subjective toxicities occurred in all HCWs, and they included nausea, fatigue, headache, and/or anorexia. Of the 10 HCWs enrolled, 6 completed 28 days of three drug therapy. Two of the six had drug dosages reduced because of symptoms but completed 28 days on the lower dose. Four discontinued prophylaxis early because of subjective toxicities. Symptomatology has not correlated with objective hematologic or biochemical toxicities. No investigator discontinued any course of chemoprophylaxis because of laboratory toxicities in a HCW.
