International Scholarly Research Notices

Review Article

New Insights into HIV/AIDS-Associated Cryptococcosis

Table 4

Summary of main clinical studies of antifungal induction phase for AIDS-associated cryptococcal meningitis since 1990.


Author, year of publication, reference	Study design/location	Drugs	Duration of treatment	Number of cases versus comparators	Clinical response (%)	Mycological response (%) or (EFA)^∧	Overall (clinical + mycological) response (%)	Mortality (%)

Larsen et al., 1990 [177]	RCT/USA	Flu (400 mg) versus AmB (0.7 mg/kg) for 1 week then three-times weekly + 5FC (150 mg/kg)	10 weeks	14 versus 6	63	75	43 versus 100	19 versus 0 ()

Saag et al., 1992 [74]	RCT (2 : 1)/USA	Flu (200 mg) versus AmB (0.4 mg/kg)	10 weeks	131 versus 63	60 versus 67	43 versus 46 (10 weeks)	44 versus 40	15 versus 8 (2 weeks) 14 versus 18

De Gans et al., 1992 [178]	RCT (non-blinded)/The Netherlands	Itra (400 mg) versus AmB (0.3 mg/kg) + 5FC (150 mg/kg)	6 weeks	12 versus 10	NR	NR	42 versus 100	0

Coker et al., 1993 [179]	OS/Multicentre (Europe)	LAMB (4 mg/kg/d)	2 weeks	23	74	66.7	NR	0

Menichetti et al., 1996 [180]	Cohort/Italy	Flu (800–1000 mg/d)	3 weeks	14	54.5 (10 weeks)	NR	67.1	18.2

van Der Horst et al., 1997 [76]	RCT/USA	AmB (0.7 mg/kg) + 5FC (100 mg/kg) versus AmB (0.7 mg/kg)	2 weeks	202 versus 179	78 versus 83	60 versus 51 (2 weeks)	NR	Overall 5.5 (2 weeks); 3.9 (10 weeks)

Leenders et al., 1997 [181]	RCT/The Netherlands	L-AmB (4 mg/kg) versus Amb (0.7 mg/kg)	3 weeks	15 versus 13	87 versus 83 (10 weeks)	73 versus 38 (3 weeks)		Overall 10.7

Mayanja-Kizza et al., 1998 [182]	RCT/Uganda	Flu (200 mg/d) + 5FC (150 mg/kg/d) versus Flu (200 mg/d)	8 weeks	30 versus 28	NR	NR	32 versus 12	60 versus 84 (2 weeks); 68 versus 88 (6 months)

Brouwer et al., 2004 [183]	RCT/Thailand	AmB (0.7 mg/kg) + FC (100 mg/kg) versus AmB (0.7 mg/kg) versus AmB (0.7 mg/kg) + Flu (400 mg) + FC (100 mg/kg) versus AmB (0.7 mg/kg) + Flu (400 mg)	2 weeks	15 versus 16 versus 16 versus 16	NR	−0.54 versus –0.31 versus –0.38 versus –0.39^∧	64 (10 weeks)	Overall 14.6 (2 weeks); 21.9 (10 weeks)

Schaars et al., 2006 [85]	Retrospective chart review/South Africa	Flu (200 mg/d) year 1991–2000 Flu (400 mg/d) 2001		77 versus 128	NR	NR	NR	23.4 versus 26.6

Bicanic et al., 2007 [184]	POT/South Africa	AmB (1 mg/kg) versus Flu 400 mg	10 weeks	49 versus 5	67 versus 25*	−0.48 versus –0.02^∧	38 versus 0^†	Overall mortality 17 (2 weeks); 37 (10 weeks)

Bicanic et al., 2008 [185]	RCT/South Africa	AmB (1 mg/kg) + 5FC (100 mg) versus AmB (0.7 mg/kg) + 5FC (100 mg)	2 weeks	34 versus 30	74 versus 79*	−0.56 versus –0.45^∧	60^†	3 versus 9 (2 weeks); 21 versus 26 (10 weeks). Overall mortality 24 (10 weeks) and no differences between groups

Longley et al., 2008 [186]	Cohort/Uganda	Flu (800 mg) versus Flu (1200 mg) then 400 mg	2 weeks + 8 weeks	30 versus 30	NR	−0.07 versus –0.18^∧	40 versus 52*	37 versus 22 (2 weeks) 60 versus 48 (10 weeks)

Dammert et al., 2008 [187]	Cohort/Perù	AmB (0.7 mg/kg/d)	2-3 weeks	47	NR	25 (2 weeks) 68 (10 weeks)	70 (10 weeks)	13 (2 weeks) 22 (10 weeks)

Pappas et al., 2009 [188]	RCT/USA and Thailand	AmB (0.7 mg/kg) versus AmB (0.7 mg/kg) + Flu (400 mg) versus AmB (0.7 mg/kg) + Flu (800 mg)	2 weeks	46 versus 48 versus 41	42.5 versus 28.3 versus 52.3	NR	71.4 versus 84.2 versus 83.3 (10 weeks)	22 versus 17 versus 18.4 (10 weeks)

Hamill et al., 2010 [189]	RCT/USA and Canada	LamB (3 mg/kg/d) versus LamB (6 mg/kg/d) versus AmB (0.7 mg/kg/d)	2 weeks (11–21 days)	86 versus 94 versus 87	65.8 versus 75.3 versus 65.8 (2 weeks) 70.5 versus 72.9 versus 81.5 (10 weeks)	58.3 versus 48 versus 47.5 (2 weeks) 60 versus 70.7 versus 78.7	67.5 versus 73.7 versus 75.5 (10 weeks)	14 versus 9.6 versus 11.5 (10 weeks) Overall mortality at 10 weeks 11.6%

Lightowler et al., 2010 [190]	Cohort/South Africa	AmB (0.7 mg/kg/d) versus Flu (400 mg/d)	2 weeks	148 versus 28	NR	NR	Fluconazole associated with 5.1 RR of death at 28 days	Overall 28 (2 weeks); 32.3 (10 weeks)

Falci et al., 2010 [191]	Pilot/Brazil	AmB (0.7 mg/kg/d) continuous infusion (24-h) + FC (100 mg/k/d)	2 weeks	12	NR	−0.37^∧	80	10 (2 weeks); 10 (10 weeks)

Nussbaum et al., 2010 [192]	RCT/Malawi	Flu (1200 mg/d) versus Flu (1200 mg/d) + FC (100 mg/kg/d)	2 weeks	20 versus 21	NR	−0.11 versus −0.28^∧	NR	10 versus 37 (2 weeks); 43 versus 58 (10 weeks) Overall 48.8

Jadhav et al., 2010 [193]	RCT/India	LamB (1 mg/kg) versus LamB (3 mg/kg)	3 weeks	11 versus 15	NR	NR	36.6 versus 54	Overall 27 (10 weeks)

Loyse et al., 2012 [194]	RCT/South Africa	AmB (0.7–1 mg/kg) + 5FC (100 mg/d) versus AmB (0.7–1 mg/kg/d) + Flu (800 mg/d) versus AmB (0.7–1 mg/kg) + Flu (1200 mg/d) versus AmB (0.7–1 mg/kg) + Vor (600 mg/d)	2 weeks	21 versus 22 versus 24 versus 14	NR	−0.41 versus −0.38 versus −0.41 versus −0.44^∧	NR	Overall 12 (2 weeks); 29 (10 weeks) (no statistically significant differences among groups)

Muzoora et al., 2012 [195]	Cohort/Uganda	Flu (1200 mg/d) + AmB (1 mg/kg/d)	2 weeks	30	NR	−0.31 (2 weeks)^∧	NR	23 (2 weeks); 28 (10 weeks)

Jarvis et al., 2012 [196]	RCT/South Africa	AmB (1 mg/kg/d) + 5FC (100 mg/kg/d) versus AmB (1 mg/kg/d) + 5FC (100 mg/kg/d) + IFNγ (100 μg) 2 doses versus AmB (1 mg/kg/d) + 5FC (100 mg/kg/d) + IFNγ (100 μg) 6 doses	2 weeks	31 versus 29 versus 30	NR	−0.49 versus 0.64 versus −0.64^∧	NR	32 versus 33 versus 27 (10 weeks) Overall 14 (2 weeks) 27 (10 weeks)

Jackson et al., 2012 [197]	RCT/Malawi	Flu (1200 mg/d) + AmB (1 mg/kg/d) versus Flu (1200 mg/d) + 5FC (100 mg/kg/d) + AmB (1 mg/kg/d for 7 days)	2 weeks	20 versus 20	NR	−0.38 versus −0.50^∧	NR	No statistically significant differences at 2 and 10 weeks between the arms

RCT: randomized controlled trial; OS: open label study; NR: not reported; EFA: early fungicidal activity ^∧expressed as mean log CFU/mL; Flu: fluconazole; amB: amphotericin B deox; Itra: itraconazole; 5FC: 5-fluorocytosine; LAMB: liposomal amphotericin B; IFNγ: interferon-gamma; Vor: voriconazole; *percentage of patients surviving at weeks 10: ^†proportion of patients surviving after 1 year of followup.