Risk for immune-mediated liver reactions by nevirapine revisited

Implementation of combination antiretroviral therapies has transformed the prognosis of HIV infection during the past decade. Because of its low-pill burden, convenient administration once or twice daily without food restrictions and, in the case of nevirapine, favorable metabolic profile and proven safety in pregnant women and newborns, nonnucleoside reverse transcriptase inhibitors have been shown to be often superior to protease inhibitors as third agents in combination with a backbone of two nucleoside reverse transcriptase inhibitors. Therefore, two nucleoside reverse transcriptase inhibitors plus one nonnucleoside reverse transcriptase inhibitor are currently the most popular used first-line therapies. Hepatotoxicity during the first weeks of therapy with nevirapine, particularly when initiated in women with CD4 counts > 250 cells/mm3, has prompted changes in guidelines and led to a modification in the product label. Recent data, however, suggest that virologically suppressed patients under any other antiretroviral drug combination may safely switch to nevirapine as a part of a simplification strategy, regardless of their current CD4 count. This subset of patients does not show an increased risk of hepatotoxicity or rash with elevated CD4 counts, as has been reported in drug-naive HIV persons. This information is important and may expand the number of candidates who could benefit from nevirapine use, since a substantial proportion of HIV patients show metabolic abnormalities (dyslipidemia, insulin resistance, liver steatosis) and are at increased cardiovascular risk. Fortunately, many of these conditions may ameliorate or improve using nevirapine.