Summary of findings 1. Induction: liposomal amphotericin compared with amphotericin deoxycholate.
| Liposomal amphotericin compared with amphotericin deoxycholate for induction therapy of progressive disseminated histoplasmosis | ||||||
|
Patient or population: adults with HIV and progressive disseminated histoplasmosis Settings: endemic areas Intervention: induction therapy with liposomal amphotericin B Comparison: amphotericin B deoxycholate | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | Number of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| dAmB | lAmB | |||||
| Clinical success | 560 per 1000 | 818 per 1000 (566 to 1000) | RR 1.46 (1.01 to 2.11) | 80 (1 study) | ⊕⊕⊝⊝ Lowa | Compared to dAmB, lAmB may have higher clinical success rates. |
| Death | 125 per 1000 | 19 per 1000 (3 to 173) | RR 0.15 (0.02 to 1.38) | 77 (1 study) | ⊕⊕⊝⊝ Lowb |
Treatment with lAmB may result in lower mortality than treatment with dAmB. |
| Safety outcomes: nephrotoxicity | 375 per 1000 | 94 per 1000 (34 to 251) | RR 0.25 (0.09 to 0.67) | 77 (1 study) | ⊕⊕⊕⊕ High |
Treatment with lAmB resulted in lower rates of nephrotoxicity compared to treatment with dAmB; this was supported by findings of a Cochrane Review which reported moderate‐certainty evidence (Botero Aguirre 2015). |
| Safety outcomes: drug discontinuation | 83 per 1000 | 19 per 1000 (2 to 198) | RR 0.23 (0.02 to 2.38) | 77 (1 study) | ⊕⊝⊝⊝ Very lowc | We do not know if treatment with lAmB leads to fewer treatment discontinuations than dAmB. |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; dAmB: deoxycholate amphotericin B; lAmB: liposomal amphotericin B; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate. | ||||||
aDowngraded two levels for very serious imprecision: the CI met the line of no effect and was based on very few events (73 participants, 1 randomized controlled trial). bDowngraded two levels for very serious imprecision: the CIs were wide and crossed the line of no effect. cDowngraded one level for serious risk of bias (due to unclear reporting criteria) and two levels for very serious imprecision (the CIs were wide and crossed the line of no effect).