[56] INCIDENCE AND RISK FACTORS FOR SEVERE ADVERSE EVENTS IN A PROSPECTIVE COHORT OF HIV-INFECTED ADULTS STARTED ON A PROTEASE INHIBITOR-CONTAINING THERAPY

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] INCIDENCE AND RISK FACTORS FOR SEVERE ADVERSE EVENTS IN A PROSPECTIVE COHORT OF HIV-INFECTED ADULTS STARTED ON A PROTEASE INHIBITOR-CONTAINING THERAPY

[AUTHOR(S):] X Duval¹, V Journot², T May³, C Charlois¹, A Waldner⁴, C Merle de Boever⁶, C Barennes², JM Ragnaud⁵, G Chêne², C Leport¹ and the APROCO Study Group
¹Bichat Claude Bernard Hospital Paris,France; ²Inserm U 330 Bordeaux, France; ³CHU de Brabois, Nancy,France; ⁴CHU Reims, France; ⁵Groupe Hospîtalier Pellegrin, Bordeaux, France; and ⁶ CISIH Montpellier, France

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 56
Antiviral Therapy 2003; 8(Suppl. 1):S197

[ABSTRACT:] Objective: To study the incidence of SAE and their risk factors in a large multicentre cohort including 1155 pts starting on protease inhibitor (PI) between May 1997 and June 1998.

Methods: SAE (grade 3 or 4 events, except lipodystrophy) were prospectively reported and validated by two clinical experts; the likelihood of resulting from ARV treatment was classified as related or unrelated to PI and/or other ARV. This analysis reports data on PI-related SAE occurring in the first 2 years of follow-up occurring with the first received PI.

Results: At baseline, 44% of pts initiated an indinavircontaining regimen, 25% nelfinavir, 16% ritonavir, 11% saquinavir and 4% other PI regimen. During a median follow-up of 23 months (2037 pt-years), 550 events were reported, 235 were related to ARV and 169 to PI (8% pt-years). Overall, 20% occurred within the first month and 51% within the first 4 months after initiation of therapy. The most frequent SAE related to PI involved the liver (31%), the kidney (18%), the haematological system (14%) and metabolic parameters (11%). In a multivariate proportional hazard model, creatininaemia clearance <70 ml/min [HR=2.11, 95% confidence interval (CI): 1.21–3.67) P=0.007], increase of ASAT (for additional 100 UI/l, HR=1.60, CI: 1.31–1.96, P=10-4), hepatitis C and/or B coinfection (HR=2.56, CI: 1.76–3.72, P=10-4), HIV viral load >5 (log copies/ml) (HR=1.54, 95%CI: 1.06–2.25) P=0.03), indinavir initiation at baseline (HR=1.69, CI: 1.16–2.44, P=0.008) were associated with an higher risk of SAE.

Conclusions: SAE after the initiation of HAART are frequent and related both to host (renal, hepatic tests and hepatitis co-infections) and treatments characteristics. Early occurrence of SAE in the course of therapy could involve for some of them a toxic mechanism, with decreasing risk over time.

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