This is an unblinded, voluntary, open-label toxicity trial assessing combination antiretroviral therapy of zidovudine plus lamivudine and, when indicated, indinavir or nelfinavir as agents for post-exposure chemoprophylaxis for healthcare work-ers (HCWs) sustaining occupational exposures to human immunodeficiency virus (HIV). Indinavir or nelfinavir may be added when the exposure is especially severe or when drug-resistant HIV is suspected. 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. Antiretroviral drugs are initiated as soon as possible for the exposed HCW, but no longer than 72 hours post-exposure, 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. From 10/01/98 to 06/17/99, five HCWs at NIH elected chemoprophylaxis on the protocol. Four HCWs were started on three drugs, and one HCW was started on two drugs. Three of the five reported subjective toxicities, which included nausea, fatigue, headache, dyspepsia, or myalgia. None of the five completed 28 days. One discontinued because the injury source was found to be HIV-negative; three discontinued because of subjective toxicities; one began three- drug therapy recently and has not yet completed 28 days of therapy. Symptomatology has not correlated with any objective hematologic or biochemical toxicities. We have not identified HIV infection among NIH study participants. - Human Subjects
