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.
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.
Chirgwin
Keith
K
Department of Medicine, State University of New York at Brooklyn, NY, USA. keith_chirgwin@merck.com
Hafner
Richard
R
Leport
Catherine
C
Remington
Jack
J
Andersen
Janet
J
Bosler
Elizabeth M
EM
Roque
Clemente
C
Rajicic
Natasa
N
McAuliffe
Vincent
V
Morlat
Philippe
P
Jayaweera
D T
DT
Vilde
Jean-Louis
JL
Luft
Benjamin J
BJ
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
D000981:Antiprotozoal Agents; D009285:Naphthoquinones; D013411:Sulfadiazine; D053626:Atovaquone; D011739:Pyrimethamine