Carbamazepine-indinavir interaction causes antiretroviral therapy failure

OBJECTIVE: TO report a case of antiretroviral therapy failure caused by an interaction between carbamazepine and indinavir. CASE SUMMARY: A 48-year-old HIV-positive white man was treated with antiret roviral triple therapy, consisting of indinavir, zidovudine, and lamivudine . His HIV-RNA (viral load) became undetectable (<400 copies/mL) less than t wo months after this therapy was started; this was confirmed one month late r. Shortly after the start of antiretroviral therapy, the patient developed herpes tester, which was treated with famciclovir. Tramadol was initially prescribed for postherpetic neuralgia; however, this was substituted with c arbamazepine due to insufficient analgesic effect. Indinavir plasma concent rations decreased substantially during carbamazepine therapy. Carbamazepine was stopped after 2.5 months and, two weeks later, the HIV-RNA was detecta ble (6 x 10(3) copies/mL). Resistance for lamivudine was observed in that b lood sample; resistance for zidovudine might have been present, and resista nce to indinavir was not detected. A few months later, a further increase o f the HIV-RNA occurred (300 x 10(3) copies/mL), after which the therapy was switched to a new antiretroviral regimen containing nevirapine, didanosine , and stavudine. DISCUSSION: Physicians may prescribe carbamazepine for HIV-infected patient s to treat seizures or postherpetic neuralgia, which are complications of o pportunistic infections such as herpes tester or toxoplasmosis. Carbamazepi ne is a potent enzyme inducer, predominantly of the CYP3A enzyme system, wh ile HIV-protease inhibitors such as indinavir are substrates for and inhibi tors of CYP3A. Therefore, an interaction between these drugs could be expec ted. A low dose of carbamazepine (200 mg/d) and the usual dose of indinavir (800 mg q8h) in our patient resulted in carbamazepine concentrations withi n the therapeutic range for epilepsy treatment; indinavir concentrations dr opped substantially. The virologic, resistance, and plasma drug concentrati on data, as well as the chronology of events, are highly indicative of anti retroviral treatment failure due to the interaction between carbamazepine a nd indinavir. CONCLUSIONS: Concomitant use of carbamazepine and indinavir may cause failu re of antiretroviral therapy due to insufficient indinavir plasma concentra tions. Drugs other than carbamazepine should be considered to prevent this interaction. Amitriptyline or gabapentin are alternatives for postherpetic neuralgia; valproic acid or lamotrigine are alternatives for seizures. When alternate drug therapy is not possible, dosage adjustments, therapeutic dr ug monitoring, and careful clinical observation may help reduce adverse cli nical consequences.