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.
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.
Miro
Jose M
JM
Institut d'Investigacions Biomediques August Pi-Sunyer-Hospital Clinic, University of Barcelona, Barcelona, Spain. jmmiro@ub.edu
Lopez
Juan C
JC
Podzamczer
Daniel
D
Peña
Jose M
JM
Alberdi
Juan C
JC
Martínez
Esteban
E
Domingo
Pere
P
Cosin
Jaime
J
Claramonte
Xavier
X
Arribas
Jose R
JR
Santín
Miguel
M
Ribera
Esteban
E
D000328:Adult; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D008297:Male; D012367:RNA, Viral; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control*
D019380:Anti-HIV Agents; D012367:RNA, Viral