Severe weight loss in HIV / HCV-coinfected patients treated with interferon plus ribavirin: incidence and risk factors F. Bani-Sadr, 1 N. Lapidus, 1 J.-C. Melchior, 2 I. Ravaux, 3 M. Bensalem, 4 I. Rosa, 5 P. Cacoub, 6 S. Pol, 7 C. Perronne 2 and F. Carrat 1 1 Groupe Hospitalier Universitaire Est, Universite´ Paris 6, INSERM U707, Paris; 2 Universite´ de Versailles, Hoˆpital Raymond Poincare´, Garches; 3 Hoˆpital de la Conception, Marseille; 4 Centre Hospitalier Re´gional dÕAnnecy, Annecy; 5 Hoˆpital Intercommunal de Cre´teil, Cre´teil; 6 Groupe Hospitalier Universitaire Est, Universite´ Paris 6, UMR7087, Paris; and 7 Groupe Hospitalier Universitaire Ouest, Universite´ Paris 5, INSERM U370, Paris Received 15 June 2007; accepted for publication 7 September 2007 SUMMARY. Weight loss is reported by more than 20% of hepatitis C virus (HCV)-monoinfected patients treated with the peg-interferon (peg-IFN) and ribavirin combination. The aim of this study was to determine the incidence and risk factors of severe weight loss (‡10%) in human immuno- deficiency virus (HIV) / HCV-coinfected patients participating in a randomized, controlled 48-week trial comparing peg- IFN alpha 2b plus ribavirin with IFN alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, anti-HCV therapy and clinical and laboratory findings. One hundred eleven (28.9%) of 383 patients who received at least one dose of anti-HCV treatment subsequently had severe weight loss. Among patients who took at least 80% of the planned total dose, severe weight loss occurred in 74 patients (32.7%). In multivariate analysis, age >40 years [hazard ratio (HR), 1.59; 95% CI 1.09 to 2.31; P = 0.016], body mass index (BMI) >22 (HR, 1.72; 95% CI, 1.16 to 2.55; P = 0.0069), peg-IFN alpha-2b (HR, 1.82; 95% CI, 1.24 to 2.69; P = 0.0022) and female sex (HR, 1.60; 95% CI, 1.05 to 2.43; P = 0.027) were associated with severe weight loss. In contrast, patients taking non-nucleoside reverse trans- criptase inhibitors (NNRTI)-containing antiretroviral regi- mens were less likely to lose weight (HR, 0.62; 95% CI, 0.39 to 0.96; P = 0.034). Lipodystrophy tended to occur more frequently in patients who had severe weight loss than in the other patients (26.1% vs 17.6%; P = 0.0682) and patients whose weight loss >5% persisted 24 weeks after the com- pletion of anti-HCV therapy (n = 58 / 111) were more likely to be receiving stavudine-based antiretroviral therapy, sug- gesting that mitochondrial toxicity plays some role in weight loss. These findings show that severe weight loss is a fre- quent side effect of anti-HCV therapy in HIV / HCV-coinfected patients. The underlying mechanisms remain to be identi- fied. Keywords: HIV / HCV coinfection, non-nucleoside reverse transcriptase inhibitor, peg-interferon, weight loss. The pathogenesis of weight loss in human immunodefi- ciency virus (HIV) / hepatitis C virus (HCV)-coinfected pa- tients is multifactorial. Both HIV and chronic HCV infection induce a hypermetabolic / hypercatabolic state associated with weight loss [1,2]. Antiretroviral therapy can lead to lipoatrophy and weight loss and weight loss is reported by more than 20% of HCV-monoinfected patients treated with the peg-interferon (peg-IFN) and ribavirin combination [3]. The degree and possible determinants of weight loss during anti-HCV therapy in HIV / HCV-coinfected patients are poorly documented. The aim of this study was to determine the incidence and risk factors of severe weight loss (‡10%) in HIV / HCV-co- infected patients participating in a large randomized con- trolled trial comparing pegylated interferon alpha-2b plus ribavirin with conventional interferon alpha-2b plus ribavi- rin for 48 weeks (the ANRS HC02 RIBAVIC study)[4]. METHODS The results of the ANRS HC02 RIBAVIC study have been reported in detail elsewhere [4]. Only the 383 patients who received at least one dose of study medication (weekly subcutaneous injections of 1.5 lg / kg peg-IFN alpha-2b Abbreviations: BMI, body mass index; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HR, hazard ratio; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitors; peg-IFN, peg-interferon; PI, protease inhibitors. Correspondence: Dr. Firouze´ BANI-SADR, INSERM U707, Faculte´ de Me´decine Hoˆpital Saint Antoine, 27 rue de Chaligny, 75 475 Paris Cedex 12-France, Tel.: (33) 1 44 73 84 40, Fax: (33) 1 44 73 84 53. E-mail: firouze.bani-sadr@tnn.ap-hop-paris.fr Journal of Viral Hepatitis, 2008, 15, 255–260 doi:10.1111/j.1365-2893.2007.00939.x Ó 2007 The Authors Journal compilation Ó 2007 Blackwell Publishing Ltd