Safety of Switching Nevirapine Twice Daily to Nevirapine Once Daily in Virologically Suppressed Patients.

BACKGROUND: The strategy of switching nevirapine (NVP) twice daily to once daily was evaluated. METHODS: Forty-eight-week randomized, open, multicenter trial. Stable HIV-infected patients on NVP twice daily for >12-18 weeks with alanine aminotransferase (ALT) <2.5, the upper normal limit were randomized to continue their regimen or switch to NVP 400 mg once daily. Primary end point was the proportion of ALT/aspartate transaminase (AST) > or =grade 3. RESULTS: 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 3/4 ALT/AST increases, but in 2 of them (once daily), transaminases decreased despite continuation with NVP. Two other once daily patients presented grade 3/4 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%). CONCLUSIONS: 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.

Avascular necrosis in HIV-infected patients receiving antiretroviral treatment: study of seven cases.

PURPOSE: We analyzed clinical, radiological, scintigraphical, epidemiological, and immunological data in a group of HIV-infected patients with osteonecrosis. METHOD: The first case was diagnosed in June 1997, and 6 more were identified thereafter among 1,650 attended patients (0.36%). Mean age was 37.6 years (33-46), and all were men. Mean CD4+ lymphocyte count was 501 cells/microL (98-1156), viral load was undetectable (<50 copies/mL) in 5 patients, and only 2 had AIDS diagnosis. Two patients were alcohol abusers, 1 received corticosteroids, and 3 had hypertrigliceridemia. One patient was treated with d4T plus 3TC, and the remaining received HAART. In 2 patients, lipodystrophy was simultaneously diagnosed. RESULTS: Mean time between first dose of antiretroviral drugs and onset of symptoms was 12 months (2-24). All patients developed pain and functional impotence of the affected joints, and the diagnosis was confirmed by imaging techniques. Distribution of the affected sites was as follows: both hips in 5 cases, femoral external condyle in 1, and multiple joints in 1. In 4 cases, the protease inhibitor was interrupted; there was clinical improvement in 2 of these cases. The unfavorable outcome of the remaining cases required surgical intervention. CONCLUSION: Metabolic and bone diseases should be considered a complication of HIV infection that is of growing importance.