ORIGINAL ARTICLE HIV Safety and effectiveness of raltegravir in patients with haemophilia and anti-HIV multidrug resistance L. MANGIAFICO, M. PERJA, F. FUSCO, S. RIVA, D. MAGO and A. GRINGERI Department of Internal Medicine, Universita ` degli Studi di Milano and Fondazione IRCCS Ca ` Granda Ospedale Maggiore Policlinico, Milan, Italy Summary. Highly active antiretroviral therapy (HA- ART) of HIV+ patients with haemophilia poses specific questions on safety and effectiveness because of long- lasting HIV infection, multidrug resistance, concomi- tant chronic liver disease and bleeding risk. Raltegravir belongs to a new class of drugs that inhibits HIV integrase and is known to have a good effectiveness and safety profile. The aim of this study was to evaluate safety and effectiveness of HAART with raltegravir in patients with haemophilia. HIV+ patients with haemo- philia treated with raltegravir for ‡6 months were included in this retrospective study. Safety criteria were: occurrence of any adverse event, unexpected blood test abnormalities and increased consumption of coagula- tion factors. Effectiveness criteria were: no disease progression, viral load <40 HIV-RNA copies mL )1 and increased or stable CD3+ CD4+ cell count above 200 cells cmm )1 . Seven patients with HCV co-infection underwent treatment with raltegravir for a median of 20 months (min–max: 7–30). Before starting treatment with raltegravir, three patients had CD3+ CD4+ cell counts <200 cells cmm )1 . The median viral load was 7547 copies mL )1 (min–max: <40–37 807). During treatment, no new sign of disease progression was observed. All patients showed suppression of viral replication (<40 HIV-RNA copies mL )1 ). CD3+ CD4+ cell counts showed a median increase of 152 cells cmm )1 (min–max: 40–525). Two patients suffered from periph- eral neuropathy, which was deemed as possibly associ- ated with raltegravir. There was no evidence of increased bleeding frequency, modification of bleeding sites and lack of response to replacement therapy. Raltegravir- based HAART appeared to be effective and generally well-tolerated in patients with haemophilia, and it might represent a useful option in these patients. Keywords: effectiveness, HAART, haemophilia, HIV, raltegravir, safety Introduction Italian patients with haemophilia treated with plasma- derived coagulation factor concentrates (CFC) had been exposed to HIV between 1979 and 1985, and 60% of them got the infection [1]. Before 1996, when protease inhibitors were for the first time marketed in Italy, they had undergone suboptimal antiretroviral therapy with single-drug or two-drug regimens. This therapy was anyway able to prolong the survival of these patients, half of whom were still alive when highly active antiretroviral therapy (HAART) became available [2]. The advent of HAART determined an improvement of life expectancy and quality of life of these patients; moreover, HAART was associated with a prolonged survival without end-stage liver disease in HCV coin- fected patients, at least similar to that observed in HCV positive, HIV negative patients [3]. Nevertheless, the treatment of patients with congenital bleeding disorders and HIV infection poses specific issues on treatment safety and effectiveness. In fact, the presence of long- lasting HIV infection together with inadequate regimens including mono-/dual-therapy until the advent of HAART have led to antiretroviral multi-drug resistance. In addition, all these patients have been infected with blood-borne hepatitis B and C viruses, which have caused various degrees of liver disease. For all these reasons, these patients are in great need of new drugs with no or low cross-resistance and with a better safety profile. Raltegravir (IsentressÒ; Merck Co., Whitehouse Station, NJ, USA) is the first approved inhibitor of HIV integrase, initially licensed for patients with multidrug resistance [4]. Raltegravir was shown to be Correspondence: Prof. Alessandro Gringeri, Department of Inter- nal Medicine, Universita ` degli Studi di Milano and Fondazione IRCCS Ca ` Granda, Ospedale Maggiore Policlinico, Via Pace, 9, 20122 Milan, Italy. Tel.: +39 02 5503 5290; fax: +39 02 5503 2072; e-mail: alessandro.gringeri@unimi.it Accepted after revision 12 June 2011 Haemophilia (2012), 18, 108–111 DOI: 10.1111/j.1365-2516.2011.02610.x 108 Ó 2011 Blackwell Publishing Ltd