title: A systematic review and meta-analysis of the relative efficacy and safety of treatment regimens for HIV-associated cerebral toxoplasmosis: is trimethoprim-sulfamethoxazole a real option?
abstract: The objective of this study was to perform a systematic review and meta-analysis of the literature to evaluate the efficacy and safety of therapies for cerebral toxoplasmosis in HIV-infected adults. The pyrimethamine plus sulfadiazine (P-S) combination is considered the mainstay therapy for cerebral toxoplasmosis and pyrimethamine plus clindamycin (P-C) is the most common alternative treatment. Although trimethoprim-sulfamethoxazole (TMP-SMX) has potential advantages, its use is infrequent.
  
  
  
  We searched PubMed and four other databases to identify randomized controlled trials (RCTs) and cohort studies. Two independent reviewers searched the databases, identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models.
  
  
  
  Nine studies were included (five RCTs, three retrospective cohort studies and one prospective cohort study). In comparison to P-S, treatment with P-C or TMP-SMX was associated with similar rates of partial or complete clinical response [P-C: RR 0.87; 95% confidence interval (CI) 0.70-1.08; TMP-SMX: RR 0.97; 95% CI 0.78-1.21], radiological response (P-C: RR 0.92; 95% CI 0.82-1.03), skin rash (P-C: RR 0.81; 95% CI 0.56-1.17; TMP-SMX: RR 0.17; 95% CI 0.02-1.29), gastrointestinal impairment (P-C: RR 5.16; 95% CI 0.66-40.11), and drug discontinuation because of adverse events (P-C: RR 0.32; 95% CI 0.07-1.47). Liver impairment was more frequent with P-S than P-C (P-C vs. P-S: RR 0.48; 95% CI 0.24-0.97).
  
  
  
  The current evidence fails to identify a superior regimen in terms of relative efficacy or safety for the treatment of HIV-associated cerebral toxoplasmosis. Use of TMP-SMX as preferred treatment may be consistent with the available evidence and other real-world considerations. Larger comparative studies are needed.
authors.affiliation: School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru.|Health Outcomes and Clinical Epidemiology Section, Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Hernandez
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: P
authors.initials: P
authors.lastname: Thota
authors.affiliation: Department of Infectious Diseases, Instituto de Infectologia Emilio Ribas, Sao Paulo, Brazil.
authors.forename: D
authors.initials: D
authors.lastname: Pellegrino
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: V
authors.initials: V
authors.lastname: Pasupuleti
authors.affiliation: Center for Public Health Research, Research Institute, Faculty of Medicine, Universidad de San Martin de Porres, Lima, Peru.
authors.forename: V A
authors.initials: VA
authors.lastname: Benites-Zapata
authors.affiliation: Medicine Institute Center for Value Based Care Research, Cleveland Clinic, Cleveland, OH, USA.|Department of Infectious Diseases, Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: A
authors.initials: A
authors.lastname: Deshpande
authors.affiliation: Department of Neurology, Instituto de Infectologia Emilio Ribas, Sao Paulo, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Penalva de Oliveira
authors.affiliation: Department of Neurology, Instituto de Infectologia Emilio Ribas, Sao Paulo, Brazil.|Divisão de Clínica de Moléstias Infecciosas e Parasitárias, Hospital das Clínicas, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.|Laboratório de Protozoologia, Instituto de Medicina Tropical de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: J E
authors.initials: JE
authors.lastname: Vidal
mesh_terms: D000328:Adult; D000981:Antiprotozoal Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002981:Clindamycin / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011739:Pyrimethamine / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013411:Sulfadiazine / Q000009:adverse effects / Q000627:therapeutic use; D016781:Toxoplasmosis, Cerebral / Q000188:drug therapy*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D000981:Antiprotozoal Agents; D013411:Sulfadiazine; D002981:Clindamycin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D011739:Pyrimethamine
keywords: HIV infection; cerebral toxoplasmosis; toxoplasmic encephalitis.