title: Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 Study. AIDS Clinical Trials Group 237/Agence Nationale de Recherche sur le SIDA, Essai 039.
abstract: In this international, noncomparative, randomized phase II trial, we evaluated the effectiveness and tolerance of atovaquone suspension (1500 mg orally twice daily) plus either pyrimethamine (75 mg per day after a 200-mg loading dose) or sulfadiazine (1500 mg 4 times daily) as treatment for acute disease (for 6 weeks) and as maintenance therapy (for 42 weeks) for toxoplasmic encephalitis (TE) in patients infected with human immunodeficiency virus. Twenty-one (75%) of 28 patients receiving pyrimethamine (95% lower confidence interval [CI], 58%) and 9 (82%) of 11 patients receiving sulfadiazine (95% lower CI, 53%) responded to treatment for acute disease. Of 20 patients in the maintenance phase, only 1 experienced relapse. Eleven (28%) of 40 eligible patients discontinued treatment as a result of adverse events, 9 because of nausea and vomiting or intolerance of the taste of the atovaquone suspension. Although gastrointestinal side effects were frequent, atovaquone-containing regimens are otherwise well tolerated and safe and may be useful for patients intolerant of standard regimens for toxoplasmic encephalitis.
authors.affiliation: Department of Medicine, State University of New York at Brooklyn, NY, USA. keith_chirgwin@merck.com
authors.forename: Keith
authors.initials: K
authors.lastname: Chirgwin
authors.forename: Richard
authors.initials: R
authors.lastname: Hafner
authors.forename: Catherine
authors.initials: C
authors.lastname: Leport
authors.forename: Jack
authors.initials: J
authors.lastname: Remington
authors.forename: Janet
authors.initials: J
authors.lastname: Andersen
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Bosler
authors.forename: Clemente
authors.initials: C
authors.lastname: Roque
authors.forename: Natasa
authors.initials: N
authors.lastname: Rajicic
authors.forename: Vincent
authors.initials: V
authors.lastname: McAuliffe
authors.forename: Philippe
authors.initials: P
authors.lastname: Morlat
authors.forename: D T
authors.initials: DT
authors.lastname: Jayaweera
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vilde
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Luft
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000469:parasitology; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000469:parasitology*; D000208:Acute Disease; D000328:Adult; D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053626:Atovaquone; D004359:Drug Therapy, Combination; D004660:Encephalitis / Q000188:drug therapy* / Q000469:parasitology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009285:Naphthoquinones / Q000009:adverse effects / Q000627:therapeutic use; D011739:Pyrimethamine / Q000009:adverse effects / Q000627:therapeutic use; D013411:Sulfadiazine / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D014122:Toxoplasma / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D009285:Naphthoquinones; D013411:Sulfadiazine; D053626:Atovaquone; D011739:Pyrimethamine