For people with HIV-associated cryptococcal meningitis, how do one- and two-week induction therapies compare?

Abstract

Moderate‐certainty evidence shows that mortality was probably lower and/or fungal clearance rates higher with one‐week AmBd+5FC than with two‐week regimens, although rates of anemia, hypokalemia, and alanine aminotransferase abnormalities were higher.Reviewers made six comparisons of one and two‐week induction therapies for people with HIV‐associated cryptococcal meningitis. Regimens included combinations of flucytosine (5FC), fluconazole (FLU), and amphotericin B deoxycholate (AmBd).Moderate‐certainty evidence shows that mortality was probably lower with one‐week AmBd+5FC than with two‐week regimens of AmBd+5FC, AmBd+FLU, or 5FC+FLU (differences ranged from 112 to 173 fewer deaths per 1000 people; all values on average) and was higher with one‐week AmBd+FLU than with two‐week 5FC+FLU (135 more deaths per 1000 people). Fungal clearance rates were worse with one‐week AmBd+FLU than with two‐week AmBd+5FC, better with one‐week AmBd+FLU and one‐week AmBd+5FC than with two‐week 5FC+FLU, and better with one‐week AmBd+5FC than with two‐week AmBd+FLU (range 0.07 to 0.18 log10 colony‐forming units [CFU]/mL/d). In terms of adverse events, reviewers assessed anemia, renal dysfunction, neutropenia, hypokalemia, and alanine aminotransferase (ALT) abnormality (ALT abnormality was not assessed for all comparisons). Researchers reported that fewer people developed:? anemia with two‐week 5FC+FLU than with one‐week AmBd+5FC or one‐week AmBd+FLU; and with one‐week AmBd+5FC than with two‐week AmBd+FLU or two‐week AmBd+5FC;? hypokalemia with two‐week 5FC+FLU than with one‐week AmBd+5FC or one‐week AmBd+FLU;? renal dysfunction with one‐week AmBd+5FC than with two‐week AmBd+FLU; and with two‐week 5FC+FLU than with one‐week AmBd+FLU; or? ALT abnormality with two‐week 5FC+FLU and two‐week AmBd+5FC than with one‐week AmBd+5FC.