3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 23-26 October 2001, Athens, Greece

REASONS FOR PROTEASE INHIBITOR DISCONTINUATION IN A SELECTED COHORT OF HIV-PATIENTS

Antiviral Therapy 2001; 6(Suppl. 4):30 (abstract no. 40)

P Bonfanti, T Quirino, I Faggion, L Valsecchi, S Carradori, L Pusterla, P Fortuna, L Timillero, S Miccolis, C Magnan, A Gabbuti, R Cinelli, C Martinelli,S Landonio, F Parazzini and GM Vigevani
CISAI study group

BACKGROUND: Protease inhibitors (PIs) are extremely effective anti-HIV drugs. All of them cause various adverse effects that may lead to discontinuation: poor tolerability together with treatment failure are the leading reasons for treatment interruption. Comparative data on discontinuation rates of PIs are scarce.

OBJECTIVES: To assess the probability that first PI regimen might be discontinued because of adverse events (AEs) or treatment failure.

METHODS: A prospective cohort, multicentre study on HIV-positive patients starting treatment with at least one PI after September 1997 (CISAI study). The main outcome measure was time to therapy discontinuation due to adverse events or treatment failure. We calculated Kaplan-Meier curves for PIs used. A total of 1480 patients were enrolled, with an average age of 37.1 years (SD±8.1), 1066 were male and the average follow-up time was equal to 22.2 months (range 1-30). Average CD4 lymphocytes at enrollment were 265 cell/mm³ (SD±201). From the beginning of the study to the present day (data refer to September 2000) 506 patients have left the study, 188 have been lost to follow up, 248 have definitively interrupted the therapy and 23 have died.

RESULTS: After 12 months of treatment, the percentage of patients who had interrupted treatment following AEs was 41% of ritonavir-treated patients, 22% of ritonavir-saquinavir HGC-treated patients, 17% of those treated with indinavir, and 9 and 8%, respectively, for those treated with nelfinavir and saquinavir HGC. Percentages after 24 months were the following: ritonavir 48%, ritonavir-saquinavir HGC 37%, indinavir 23%, saquinavir HGC 15% and nelfinavir 13%. Frequency rates for first treatment interruption due to treatment failure after 12 months were: ritonavir-saquinavir HGC 22%, saquinavir HGC 18%, nelfinavir 13%, ritonavir 9% and indinavir 5%. After 24 months: ritonavir-saquinavir HGC 34%, saquinavir HGC 29%, nelfinavir 17%, ritonavir 13% and indinavir 8%.

CONCLUSIONS: From the curves regarding the estimated likelihood of treatment discontinuation due to any grade of adverse reaction, ritonavir clearly emerges as the least tolerated drug, while nelfinavir is the best tolerated after 2 years. If we consider the estimated likelihood of treatment discontinuation due to treatment failure patients treated with indinavir have the lowest probability of interruption. Looking the entire cohort, the onset of AEs is the main cause of first treatment interruption.

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