Stable HIV-infected patients on NVP twice

Stable HIV-infected patients on NVP twice daily for >12-18 weeks with alanine aminotransferase (ALT) <2.5,>/=grade 3. Two hundred eighty-nine patients were included, mean CD4 620 cells per microliter. Noninferiority was demonstrated in the per protocol analysis, with 97.9% (once daily) and 99.3% (twice daily) of patients event free (difference, 1.4%; 95% confidence interval, -1.95% to 5.4%), whereas 81.8% vs. 93.8% were event free by intent-to-treat switch = toxicity analysis (difference, 12%; 95% confidence interval, 4.6% to 19.4%). Only 4 patients ( 3 once daily, 1 twice daily) had NVP-related grade ¾ ALT/AST increases, but in 2 of them (once daily), transaminases decreased despite continuation with NVP. Two other once daily patients presented grade ¾ ALT/AST increase due to well-documented acute hepatitis A virus or hepatitis C virus infection. Grade 2 ALT/AST increases occurred in 11.2% (once daily) vs. 10.3% (twice daily) of patients (P = 0.80). A larger number of once daily patients were lost to follow-up/violated protocol (15% vs. 5%). In patients on standard twice daily NVP-containing regimens for at least 12-18 weeks, per protocol analysis showed that switching to once daily NVP was not inferior to continued twice daily NVP in terms of the predefined noninferiority margin of 10% for hepatotoxicity.

Because once daily nevirapine (400 mg) may permit the design of simple once daily regimens that interfere less with daily activities, it is important to know whether it causes more toxicity than twice-daily 200 mg doses. Hypersensitivity to nevirapine in the form of liver toxicity usually presents in the first 12 to 18 weeks of treatment. If treatment guidelines are modified in the light of the findings of this and other studies, the switch to once daily nevirapine would likely not occur until after this initial period of twice-daily dosing. Independent risk factors for nevirapine-associated adverse events, such as gender, genetics, CD4 count, and hepatitis co-infection, remain considerations in prescribing antiretroviral regimens.