Answers

1. D. Lamivudine, a cytosine analogue, is a nucleoside reverse transcriptase inhibitor that acts as a competitive inhibitor of reverse transcriptase. Efavirenz is a nonnucleoside reverse transcriptase inhibitor; it acts by binding to a site adjacent to the enzyme's active site. Neither drug exhibits significant activity against HIV protease.

2. A. The NRTIs can produce a potentially fatal syndrome of lactic acidosis and severe hepatomegaly with hepatic steatosis. Risk factors associated with the development of this syndrome include female sex, obesity, alcoholism, and prolonged exposure to NRTIs. Peripheral neuropathy is a common side effect of some NRTIs (e.g., stavudine., didanosine, and zalcitabine) but not associated with these risk factors. Stevens-Johnson syndrome is rarely associated with NNRTIs, such as nevirapine, and not with these risk factors. Hyperuricemia is not associated with these risk factors. Hypersensitivity reaction may oc cur in the early months of treatment with abacavir but is not associated with this subject's risk factors.

3. A. Diazepam is metabolized in the liver by CYP3A4 and CYP2C19; efavirenz inhibits both of these isozymes and is likely to increase plasma levels of diazepam. Diazepam is almost completely converted to inactive metabolites; therefore, renal elimination is not much of a concern. Lamivudine may produce fatigue as a side effect but does not potentiate the depressant activity of diazepam. Zidovudine does not induce cytochrome P450 activity, and diazepam does not have to be converted to an active form for sedative activity.

4. C. Myelotoxicity is associated with certain NRTIs such as zidovudine. Fat redistribution, drug interactions involving CYP3A4, dyslipidemia, and diabetic symptoms are all side effects common to the protease inhibitors.

5. B. Ritonavir is a potent inhibitor of CYP3A4, the enzyme that rapidly inactivates lopinavir. This combination includes a low dose of ritonavir that is not likely to cause serious side effects but instead inhibits lopinavir metabolism. Ritonavir and lopinavir are HIV protease inhibitors and do not affect reverse transcriptase. Lopinavir is almost completely eliminated by metabolism to inactive metabolites; little is eliminated unchanged by the kidney. Lopinavir is not known to inhibit the ability of HIV to mutate. Lopinavir inhibits the enzyme HIV protease, not a structural protein.

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