Short-course amphotericin B in addition to sertraline and fluconazole for treatment of HIV-associated cryptococcal meningitis in rural Tanzania

the KIULARCO Study Group

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Cryptococcal meningitis accounts for 15% of all AIDS mortality globally. Most cases in low- and middle-income countries are treated with fluconazole monotherapy, which is associated with a high mortality. New available therapies are needed. Short-course amphotericin B has been shown to be a safe and efficient therapeutic option. Sertraline has in vitro fungicidal activity against Cryptococcus and bi-directional synergy with fluconazole. Methods: We conducted an open-label clinical trial to assess the safety and efficacy of sertraline 400 mg/day and fluconazole 1200 mg/day (n = 28) vs sertraline, fluconazole and additional 5 days of amphotericin B deoxycholate 0.7-1 mg/kg (n = 18) for cryptococcal meningitis. Results: Two-week survival was 64% (18/28) without amphotericin and 89% (16/18) with amphotericin, and 10-week survival was 21% (6/28) vs 61% (11/18), respectively (P =.012). The cerebrospinal fluid (CSF) Cryptococcus clearance rate was 0.264 log10 colony-forming units (CFU)/mL of CSF/day (95% CI: 0.112-0.416) without amphotericin and 0.473 log10 CFU/mL/day (95% CI: 0.344-0.60) with short-course amphotericin (P =.03). Sertraline was discontinued in one participant due to side effects. Four participants receiving amphotericin B experienced hypokalemia <2.4 mEq/L. Conclusions: Short-course amphotericin substantially increased CSF clearance and 10-week survival. Adjunctive sertraline improved 2-week CSF fungal clearance but did not improve 10-week mortality compared with published data using fluconazole 1200 mg/day monotherapy (early fungicidal activity 0.15 log10 CFU/mL/day).

Original languageEnglish (US)
Pages (from-to)1127-1132
Number of pages6
JournalMycoses
Volume62
Issue number12
DOIs
StatePublished - Dec 1 2019

Keywords

  • AIDS
  • HIV
  • amphotericin
  • amphotericin
  • cryptococcal meningitis
  • fluconazole
  • mortality
  • rural Tanzania
  • sertraline
  • sertraline
  • sub-Saharan Africa

PubMed: MeSH publication types

  • Clinical Trial
  • Journal Article

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