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Table 1 Characteristics of the 9 included studies

From: The prevalence of cryptococcal antigen (CrAg) and benefits of pre-emptive antifungal treatment among HIV-infected persons with CD4+ T-cell counts < 200 cells/μL: evidence based on a meta-analysis

Author, year (reference)Number of participantsStudy typeStudy durationAge (years)CD4 (cells/μL)CrAg screening methodsCM diagnostic methodsLocationTherapeutic regimensPrimary outcomes
Incidence of CMAll-cause mortality
Chariyalertsak, 2002 [18]129Prospective study104 weeks18 ~ 60<200Not reportFungal culture, a histopathological examination, or buffy coat smearThailand63 for oral itraconazole (200 mg/day) as group 1; 66 for matched placebo as group 20 in group 1; 7 in group 212 in group 1; 11 in group 2
Manfredi, 1997 [19]249Retrospective study6 years22 ~ 59<200Not reportSpecific polysaccharide antigen detection from body fluidsItaly128 for oral fluconazole (100 mg/d every third week) as group 1; 121 for no antifungal treatment as group 22 in group 1; 9 in group 212 in group 1; 13 in group 2
Parkes-Ratanshi, 2011 [20]1519Prospective study42 monthsNot report<200Not reportCrAg titre> 1:8 on two occasions, or a positive CSF CrAg or Cryptococcus neoformans grown from blood or CSF cultureUganda760 fluconazole 200 mg 3 times per week for minimum 12 weeks as group 1; 759 allocated to placebo as group 21 in group 1; 18 in group 20 in group 1; 7 in group 2
McKinsey, 1999 [21]295Randomized, placebo-Controlled studyNot report≥13<150Not reportFungal cultureNot report149 for itraconazole capsules (200 mg/day) as group 1; 146 for matched placebo as 21 in group 1; 8 in group 232 in group 1; 21 in group 2
Meya, 2010 [22]584Prospective study30 months≥18<200Not reportNot reportUgandaFluconazole (200 ~ 400 mg) for 2 ~ 4 weeks3 in CrAg+ persons and 0 in CrAg- persons6 in CrAg+ persons and 0 in CrAg- persons
Kapoor, 2015 [23]72Retrospective study15 months≥18<200LFAPositive CSF India inkSub-Saharan Africa800 mg fluconazole orally for 2 weeks, followed by 400 mg orally for 2 weeks0 in CrAg+ persons and 1 in CrAg- persons2 in CrAg+ persons and 8 in CrAg- persons
Govender, 2015a [1]1079Retrospective study19 monthsNot report< 200LA or the Latex-Cryptococcus antigen detection systemCrAg detected in CSFSouth AfricaFluconazole ranging from 400 to 800 mg per day for at least 3 monthsunknow in persons with CD4 < 200unknow in persons with CD4 < 200
Beyene, 2017 [10]783Prospective study18 months> 14≤150LFACSF CrAgEthiopiaFluconazole 800 mg/day 2 weeks, followed by 400 mg/day 8 weeks2 in CrAg+ persons and 0 in CrAg- persons4 in CrAg+ persons and 0 in CrAg- persons
Borges, 2019 [24]214Prospective study36 months> 17< 200LFAIndia ink microscopy on the CSF, CSF CrAg test and fungal cultureBrazilFluconazole 900 mg for 2 weeks, 450 mg for 8 to 10 weeks and a subsequent maintenance dose of 150–300 mg1 in CrAg+ persons with antifungal treatment and 0 in CrAg+ persons without intervention2 in CrAg+ persons
  1. “No” means “no data”; “Yes” means “data exists”; OIs means: other opportunity infections
  2. LFA Lateral flow assay, LA Latex Agglutination, LP Lumbar puncture
  3. a“Govender, 2015” study was included for evaluating the prevalence of CrAg positivity. Only the data in persons with CD4 < 200 was used