Atovaquone as long-term suppressive therapy for toxoplasmic encephalitis in patients with AIDS and multiple drug intolerance. Atovaquone Expanded Access Group.
OBJECTIVE
To evaluate the efficacy and tolerance of atovaquone used as long-term maintenance therapy in patients with toxoplasmic encephalitis and intolerant of conventional anti-Toxoplasma therapies.


METHODS
Uncontrolled open-label study of atovaquone given through an expanded access programme; statistical analysis was performed on an intent-to-treat basis.


METHODS
Sixty-five patients intolerant of conventional toxoplasmic encephalitis therapies-pyrimethamine, sulphadiazine or clindamycin-received atovaquone as maintenance therapy after resolution of an acute episode of toxoplasmic encephalitis. Patients were clinically and neurologically evaluated monthly. Toxoplasmic encephalitis relapse was defined as the occurrence of neurological abnormalities, except in the case of a proven alternative diagnosis.


RESULTS
Sixty-five patients were treated with atovaquone 750 mg four times daily and followed up for a mean period of 1 year. Mean CD4 lymphocytes count was 29 x 10(6)/l. Prior to starting atovaquone, patients had experienced a total of 129 episodes of intolerance to conventional anti-Toxoplasma drugs. Atovaquone was used as a single anti-toxoplasmic agent in 75% of the cases. Seventeen patients (26%) experienced a toxoplasmic encephalitis relapse. Sixty-three patients (97%) were able to tolerate and continued taking atovaquone. Two patients had to discontinue therapy because of side-effects. In a multivariate analysis, only the duration of pyrimethamine-sulphadiazine therapy during the acute therapy phase of toxoplasmic encephalitis was significantly associated with a decreased risk of toxoplasmic encephalitis relapse during maintenance therapy [relative risk, 0.64 for each week of pyrimethamine-sulphadiazine; 95% confidence interval (CI), 0.42-0.96; P = 0.03]. The survival probability was 70% at 1 year after the episode of toxoplasmic encephalitis (95% CI, 57-83).


CONCLUSIONS
These results suggest that atovaquone is a well-tolerated alternative anti-Toxoplasma treatment for maintenance therapy in patients who are intolerant to conventional anti-Toxoplasma drugs.
Katlama
C
C
Pitié-Salpétrière Hospital, University of Paris VI, France.
Mouthon
B
B
Gourdon
D
D
Lapierre
D
D
Rousseau
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000469:parasitology; D000328:Adult; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053626:Atovaquone; D002981:Clindamycin / Q000009:adverse effects; D004660:Encephalitis / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D009285:Naphthoquinones / Q000009:adverse effects / Q000627:therapeutic use*; D011739:Pyrimethamine / Q000009:adverse effects; D012008:Recurrence; D012307:Risk Factors; D013411:Sulfadiazine / Q000009:adverse effects; D016019:Survival Analysis; D013997:Time Factors; D016781:Toxoplasmosis, Cerebral / Q000150:complications / Q000188:drug therapy* / Q000401:mortality
D000981:Antiprotozoal Agents; D009285:Naphthoquinones; D013411:Sulfadiazine; D002981:Clindamycin; D053626:Atovaquone; D011739:Pyrimethamine