The Pharmaceutical Journal
Vol 272 No 7298 p563
8 May 2004

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Non-nucleoside combination increases risk of adverse events

Triple antiretroviral drug regimens that incorporate either nevirapine (Viramune) or efavirenz (Sustiva) show similar efficacy in patients chronically infected with HIV, according to a study published in The Lancet. However, a combination of the agents increases the risk of adverse events.

The study, called 2NN, compares the non-nucleoside reverse-transcriptase inhibitors (NNRTIs) in an open label trial involving 1,216 patients who had not previously received antiretroviral therapy. Regimens were based on the nucleoside reverse-transcriptase inhibitors stavudine (Zerit) and lamivudine (Epivir, Zeffix) plus either efavirenz (600mg daily), nevirapine (400mg once a day or 200mg twice a day) or both NNRTIs simultaneously (with a dose adjustment to 800mg of efavirenz). Treatment was considered successful at 48 weeks for 62.2 per cent of patients on efavirenz, 56.3 per cent on nevirapine twice daily, 56.4 per cent on nevirapine once daily, and 46.9 per cent in the combination group. No difference was reported for efavirenz plus nevirapine when given once or twice daily. In addition, the combination failed to improve efficacy and caused more adverse events, with patients having a higher chance of failure than those on efavirenz. Some clinicians now discourage use of the two drugs together.

In 2NN, nevirapine once daily dosing seemed as effective as twice daily, though more hepatotoxic — mostly seen as subclinical effects (2004;363:1253).

In a commentary in the same journal, Andrew Carr, St Vincent’s hospital, Sydney, Australia, says that the choice of efavirenz or nevirapine in adults starting therapy with a NNRTI should be individualised according to patient factors such as viral load, co-morbidities and adverse events. He comments that nevirapine twice daily caused hypersensitivity and hepatitis more often and more severely that efavirenz. In 2NN, 7 per cent of patients on efavirenz withdrew because of a syndrome of central nervous stimulation. Surprisingly, so did 6 per cent of nevirapine patients despite no previous reports of this syndrome with the drug. In 2NN, two deaths were related to nevirapine hepatitis and Stevens-Johnson syndrome (ibid p1248).