5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 8–11 July 2003, Le Meridien Montparnasse, Paris, France

SAFETY OF NON-NUCLEOSIDE REVERSE TRANSCRIPTASE THERAPY: DATA FROM THE EuroSIDA STUDY

Antiviral Therapy 2003; 8:L20 (abstract 24)

N Friis-MØller, O Kirk, P Reiss, A Mocroft, C Katlama, A Horban, D Banhegyi, J Gatell, B Clotet, AN Phillips and JD Lundgren for the EuroSIDA Study Group
Copenhagen HIV Programme, Hvidovre University Hospital, Hvidovre, Denmark

OBJECTIVE: To assess longer-term safety of antiretroviral treatment regimens containing non-nucleoside reverse transcriptase inhibitors (NNRTI).

METHODS: The EuroSIDA study includes 9803 patients followed prospectively at 72 centres in 26 countries across Europe. Among patients starting either nevirapine or efavirenz for the first time, the following were assessed: rate of discontinuation, reasons for discontinuation, rates of liver enzyme elevation (transaminases, AST or ALT) and severe clinical liver failure (grade III/IV hepatic encephalopathy). Discontinuation was assessed according to intervals of treatment duration of: i) 1 month; ii) 1–3; iii) 3–6; and iv) >6 months.

RESULTS: A total of 2991 patients initiated NNRTI therapy, 1648 on nevirapine and 1343 on efavirenz. Prevalence of HCV seropositivity was 33.2% and 32.1%, respectively. Within 3975 person years (PY) of follow-up until January 2002, the incidence of discontinuation per PY [95% CI] within the predefined intervals were: i) 1.04 [0.88–1.21]; ii) 0.42 [0.34–0.51]; iii) 0.41 [0.34–0.48]; and iv) 0.35 [0.32–0.44] for nevirapine, and i) 0.69 [0.55–0.84]; ii) 0.33 [0.25–0.41]; iii) 0.26 [0.20–0.33]; and iv) 0.27 [0.24–0.36] for efavirenz. At 36 months, the NNRTI was sustained in 33% and 42%, respectively (Kaplan-Meier, log-rank P<0.0001). Among collected reasons for discontinuation of nevirapine, the main reasons were rash (15.4%), other toxicities (15.1%) and failure (28.9%). Rash predominated within the first month, accounting for 56.7% of discontinuations in this interval. The main reasons for discontinuation of efavirenz were toxicity (25.0%) and failure (23.9%). The majority of toxicities were nervous system toxicity and occurred within the first 3 months of therapy. Overall, transaminases above 5 ULN was observed in 2.1% and 1.7% of patients, respectively (P=0.47). Few developed severe clinical liver failure on treatment [n=14; incidence per 100 PY, 0.3 (0.1–0.6) for nevirapine and 0.4 (0.2–0.9) for efavirenz]. Eleven out of 14 had fatal outcome and 8/11 were co-infected with hepatitis C and/or B.

CONCLUSIONS: Among patients initiating NNRTI, discontinuation of therapy was more frequently observed for nevirapine than for efavirenz. Toxicity was the predominant reason for early and failure for late discontinuation. Few cases of severe clinical liver failure were observed on either drug. The majority of fatal liver failures occurred in patients co-infected with hepatitis C and/or B.

Presenting author: N Friis-MØller

2003-07-08
24

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