didanosine and Encephalitis

In a previous work, we have showed in mice infected with an avirulent strain of Toxoplasma gondii and receiving a didanosine treatment, an important decrease of brain cysts. It is why, the purpose of this study was to investigate the effect of didanosine treatment on AIDS patients having developed Toxoplasma encephalitis. 60 patient reports were analyzed: 22 patients (group 1) did not received didanosine in their antiretroviral treatment and 38 (group 2) were treated with didanosine. The results showed that an antiretroviral therapy was prescribed for 93% of patients, 50% of them received only zidovudine and protease inhibitors were prescribed for 37%. The regimens given most frequently were those including zidovudine plus lamivudine or zidovudine plus indinavir. Among the group 1, 18% have had a relapse of Toxoplasma encephalitis. In the group 2, 37% of the patients suffered from one episode of TE while 16% have had two TE after the pause in their didanosine treatment, the maximum occurring between 4 and 24 months after the pause of didanosine. This study showed that didanosine seems to have an effect on cerebral cysts. Also, this work made a synthesis about the different treatment used in AIDS patients and the new molecules yet in development against T. gondii.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Cohort Studies; Didanosine; Drug Therapy, Combination; Encephalitis; Female; France; HIV Infections; Hospitalization; Humans; Male; Middle Aged; Prevalence; Retrospective Studies; Reverse Transcriptase Inhibitors; Toxoplasmosis, Cerebral

In this study we investigated the effect of the antiretroviral molecule 2',3'-dideoxyinosine (Videx) against cerebral cysts in a murine model of toxoplasmic encephalitis caused by a wild cystic strain of Toxoplasma gondii. The role of the vehicle was also studied. Three doses were used: 50, 100 and 150 mg/kg of body weight/day. The doses of 50 and 150 mg/kg were prepared by dissolving pure 2',3'-dideoxyinosine powder in Maalox suspension before gavaging the mice; the dose of 100 mg/kg was prepared by grinding tablets of Videx that were suspended in water. A decrease in the number of cysts and a morphological modification of them were noted from day 15 with the lowest dose. The most important decrease could be observed with the dose of 100 mg/kg/d. After 30 days of treatment with this dose, 65% of the cysts were destroyed compared to controls. For the doses of 50 and 150 mg/kg/d prepared with Maalox, 36% and 51% of the cysts were destroyed respectively. So ddI has an effect on the cerebral cysts of T. gondii even at a low dose. The galenic formulation influences its action since the doses prepared with Maalox were less efficient than those prepared from ground tablets.

Topics: Animals; Antacids; Buffers; Didanosine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Compounding; Encephalitis; Female; Mice; Toxoplasma; Toxoplasmosis, Cerebral