Discontinuation of primary and secondary Toxoplasma gondii prophylaxis is safe in HIV-infected patients after immunological restoration with highly active antiretroviral therapy: results of an open, randomized, multicenter clinical trial.

Abstract

BACKGROUND:

To our knowledge, no randomized trials have evaluated whether prophylaxis against toxoplasmic encephalitis can be safely discontinued after the CD4+ T cell count increases in response to highly active antiretroviral therapy.

METHODS:

We conducted a randomized, nonblinded, multicenter clinical trial of the discontinuation of primary or secondary prophylaxis against toxoplasmic encephalitis in human immunodeficiency virus (HIV)-infected patients with a sustained response to antiretroviral therapy (defined as a CD4+ T cell count of > or =200 cells/mm3 and a plasma HIV type 1 [HIV-1] RNA level of <5000 copies/mL for at least 3 months). Prophylaxis was restarted if the CD4+ T cell count decreased to <200 cells/mm3.

RESULTS:

The 381 patients receiving primary prophylaxis had a median CD4+ T cell count on study entry of 343 cells/mm3, and 318 (83%) of 381 patients had undetectable HIV-1 RNA in plasma. After a median follow-up period of 25 months (409 person-years), there were no episodes of toxoplasmic encephalitis among the 196 patients who discontinued prophylaxis (at 1 year, the upper limit of the 95% confidence interval for relapse rate was 2.40%). For the 57 patients receiving secondary prophylaxis, the median CD4+ T cell count on entry was 407 cells/mm3, and 49 (86%) of 57 patients had undetectable HIV-1 RNA in plasma. After a median follow-up period of 30.5 months (69 person-years), there were no episodes of toxoplasmic encephalitis among the 28 patients who discontinued prophylaxis (at 1 year, the upper limit of the 95% confidence interval for relapse rate was 16%).

CONCLUSIONS:

In HIV-infected adult patients receiving effective highly active antiretroviral therapy, primary and secondary prophylaxis against toxoplasmic encephalitis can be safely discontinued after the CD4+ T cell count has increased to > or =200 cells/mm3 for >3 months.

• Authors: Jose M Miro, Juan C Lopez, Daniel Podzamczer, Jose M Peña, Juan C Alberdi, Esteban Martínez, Pere Domingo, Jaime Cosin, Xavier Claramonte, Jose R Arribas, Miguel Santín, Esteban Ribera, GESIDA 04/98 Study Group
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 43 Issue 1 Pg. 79-89 (Jul 01 2006) ISSN: 1537-6591 [Electronic] United States
• PMID: 16758422 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• RNA, Viral

Topics

• Adult
• Animals
• Anti-HIV Agents (therapeutic use)
• Antibiotic Prophylaxis
• Antiretroviral Therapy, Highly Active
• CD4-Positive T-Lymphocytes (immunology)
• Female
• HIV Infections (complications)
• Humans
• Immune System (drug effects)
• Male
• RNA, Viral
• Toxoplasma
• Toxoplasmosis (complications, drug therapy, prevention & control)