title: Successful use of protease inhibitors in HIV-infected haemophilia patients.
abstract: The haemophilias are a group of inherited haemostatic disorders that require regular clotting factor replacement therapy in the severe and moderately severe subgroups. Prior to the introduction of adequate viral inactivation methods in 1985, haemophilia patients were at exceptionally high risk of contracting blood-borne viruses from factor concentrates as each batch was derived from the plasma of thousands of donors. As a result, approximately 60% of these patients were infected with HIV between 1979 and 1985, and HIV infection now contributes significantly to the morbidity and mortality seen in this group. Protease inhibitors (PIs) have been shown to significantly log reduce viral loads and increase CD4 cell counts in HIV-infected individuals. Recently, there has been concern about their use in HIV-infected haemophilia patients following increased bleeding episodes in some patients during PI therapy. We prospectively studied the effect of PI therapy in 20 HIV-infected haemophilia patients at our centre over a 6-month period. The mean increase in CD4 cell count was 70 x 10(6)/l and the mean log decrease in viral load was 1.59 over the study period. Gastrointestinal side-effects (nausea and vomiting in five, diarrhoea in two) were the most frequent and resulted in discontinuation of the medication in two patients. Factor concentrate usage for the group on and off study was similar. One severe FVIII patient reported a single episode of an unusual bleed which responded promptly to FVIII concentrate infusion. The significant clinical and laboratory benefits in terms of HIV disease and the paucity of added bleeding complications suggest that PI therapy should not be withheld from HIV-infected haemophilics. Further prospective studies evaluating the efficacy and possible haemostatic complications related to these promising inhibitors of the HIV protease are needed.
authors.affiliation: Department of Genito-Urinary Medicine, St James's Hospital, Dublin, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: Merry
authors.forename: C
authors.initials: C
authors.lastname: McMahon
authors.forename: M
authors.initials: M
authors.lastname: Ryan
authors.forename: E
authors.initials: E
authors.lastname: O'Shea
authors.forename: F
authors.initials: F
authors.lastname: Mulcahy
authors.forename: O P
authors.initials: OP
authors.lastname: Smith
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000139:chemically induced; D018791:CD4 Lymphocyte Count; D002177:Candidiasis / Q000139:chemically induced; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006467:Hemophilia A / Q000150:complications / Q000821:virology*; D006474:Hemorrhagic Disorders / Q000209:etiology; D006801:Humans; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000139:chemically induced; D019562:Viral Load
chemical_list: D011480:Protease Inhibitors; D012367:RNA, Viral