Toxoplasmic
encephalitis (TE) is caused by
Toxoplasma gondii infection and can be a life-threatening disease in immunocompromised patients. This study evaluated the rate of relapse associated with
pyrimethamine-based maintenance
therapy (i.e. secondary prophylaxis) in patients with human immunodeficiency virus (HIV) or
AIDs treated prior to and after the common use (i.e. 1996) of
highly active antiretroviral therapy (
HAART) (pre-
HAART and post-
HAART, respectively). PubMed, Google Scholar, and Cochrane databases were searched to 6 June 2016 using search terms:
pyrimethamine,
Daraprim,
Fansidar,
Metakelfin,
Fansimef, 5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine,
encephalitis,
cerebral, toxoplasmosis, toxoplasmic, and gondii. Single-arm cohort, retrospective, and randomized studies were included. Twenty-six studies with 1,596 patients were included in the analysis; twenty pre-
HAART (n = 1,228) studies and six post-
HAART (n = 368) were performed. Pooled proportions test for
pyrimethamine-based
therapy from pre-
HAART studies indicated a relapse rate of 19.2% and 18.9% from the fixed-effects and random-effects models, respectively. The relapse rate in the post-
HAART studies was 11.1% (fixed and random effects). Continuous
therapy was suggestive of lower incidence of relapse compared with intermittent
therapy in the pre-
HAART era (range, 18.7 to 17.3% vs. 20.9 to 25.6%, respectively). These findings indicate that the likelihood of relapse associated with
pyrimethamine-based therepy in patients with HIV and TE decreased after the introduction of
HAART to approximately 11%. The findings have important implications as relapse may affect a patient's disease severity and prognosis, increase utilization of health care resources, and result in additional health care expenditure.