The complexity of drug interactions in a case such as this and the limited knowledge of these drug-drug interactions lead to the following conclusions: 1. Plasma concentrations of the antiretroviral drugs, AEDs, and drugs using the CYP or glucuronosyl-transferase systems have to be measured. 2. Potential drug-drug interactions must be considered before the addition or discontinuation of any drugs used by an HIV-infected patient on a multidrug treatment regimen. Treatment of these patients with complex drug regimens and medical conditions must be approached in a logical fashion. First, the metabolic pathways for all drugs used should be tabulated. Next, the known effects of each drug (inhibition, induction, or autoinduction) on other drugs used in the treatment regimen should be reviewed. The consequences of adding, removing, or altering the doses of any drug should be considered. As few data are available to predict the magnitude of changes, serum concentrations of all drugs must be determined before changes are made. Then, after 1-2 weeks, measurements should be repeated and dose adjustments made as needed. When choosing AEDs, those with little or no drug-drug interactions should be given priority if they have an appropriate efficacy profile. Clearly, AEDs that use the CYP system extensively are problematic in these complex cases. In addition, valproate may pose a risk of hepatic failure when used with the antiretroviral drugs used to treat HIV.
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