Comparative effectiveness of induction therapy for human immunodeficiency virus-associated cryptococcal meningitis: A network meta-analysis

Jeffrey I. Campbell, Steve Kanters, John E. Bennett, Kristian Thorlund, Alexander C. Tsai, Edward J. Mills, Mark J. Siedner

Research output: Contribution to journalArticle

Abstract

Background. Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin- fluconazole. Methods. We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine + triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results. In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not identify a benefit for combination therapy in restricted analyses in either resource- rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions. Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virusassociated cryptococcal meningitis.

Original languageEnglish (US)
Article numberofv010
JournalOpen Forum Infectious Diseases
Volume2
Issue number1
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Cryptococcal Meningitis
Amphotericin B
HIV
Flucytosine
Triazoles
Therapeutics
Mortality
Fluconazole
Network Meta-Analysis
Consciousness Disorders
Drug-Related Side Effects and Adverse Reactions
PubMed

Keywords

  • Cryptococcal meningitis
  • HIV/AIDS
  • Induction therapy
  • Network meta-analysis
  • Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

Cite this

Comparative effectiveness of induction therapy for human immunodeficiency virus-associated cryptococcal meningitis : A network meta-analysis. / Campbell, Jeffrey I.; Kanters, Steve; Bennett, John E.; Thorlund, Kristian; Tsai, Alexander C.; Mills, Edward J.; Siedner, Mark J.

In: Open Forum Infectious Diseases, Vol. 2, No. 1, ofv010, 2015.

Research output: Contribution to journalArticle

Campbell, Jeffrey I. ; Kanters, Steve ; Bennett, John E. ; Thorlund, Kristian ; Tsai, Alexander C. ; Mills, Edward J. ; Siedner, Mark J. / Comparative effectiveness of induction therapy for human immunodeficiency virus-associated cryptococcal meningitis : A network meta-analysis. In: Open Forum Infectious Diseases. 2015 ; Vol. 2, No. 1.
@article{6160e1e59722459590b75aa3ccf5364f,
title = "Comparative effectiveness of induction therapy for human immunodeficiency virus-associated cryptococcal meningitis: A network meta-analysis",
abstract = "Background. Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin- fluconazole. Methods. We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine + triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results. In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not identify a benefit for combination therapy in restricted analyses in either resource- rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions. Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virusassociated cryptococcal meningitis.",
keywords = "Cryptococcal meningitis, HIV/AIDS, Induction therapy, Network meta-analysis, Therapeutics",
author = "Campbell, {Jeffrey I.} and Steve Kanters and Bennett, {John E.} and Kristian Thorlund and Tsai, {Alexander C.} and Mills, {Edward J.} and Siedner, {Mark J.}",
year = "2015",
doi = "10.1093/ofid/ofv010",
language = "English (US)",
volume = "2",
journal = "Open Forum Infectious Diseases",
issn = "2328-8957",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Comparative effectiveness of induction therapy for human immunodeficiency virus-associated cryptococcal meningitis

T2 - A network meta-analysis

AU - Campbell, Jeffrey I.

AU - Kanters, Steve

AU - Bennett, John E.

AU - Thorlund, Kristian

AU - Tsai, Alexander C.

AU - Mills, Edward J.

AU - Siedner, Mark J.

PY - 2015

Y1 - 2015

N2 - Background. Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin- fluconazole. Methods. We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine + triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results. In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not identify a benefit for combination therapy in restricted analyses in either resource- rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions. Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virusassociated cryptococcal meningitis.

AB - Background. Multiple international treatment guidelines recommend amphotericin-based combination regimens for induction therapy of cryptococcal meningitis. Yet, only 1 trial has reported a mortality benefit for combination amphotericin-flucytosine, and none have reported a mortality benefit for combination amphotericin- fluconazole. Methods. We conducted a Bayesian network meta-analysis to estimate the comparative effectiveness of recommended induction therapies for HIV-associated cryptococcal meningitis. We searched PubMed and Cochrane CENTRAL for clinical reports of induction therapy for HIV-associated cryptococcal meningitis. We extracted or calculated early (two-week) and late (six to 12-week) mortality by treatment arm for the following induction regimens: amphotericin B alone, amphotericin B + flucytosine, amphotericin B + triazoles, amphotericin B + flucytosine + triazoles, triazoles alone, triazoles + flucytosine, liposomal amphotericin B, and amphotericin B + other medicines. Results. In the overall sample (35 studies, n = 2483), we found no evidence of decreased mortality from addition of flucytosine or triazoles to amphotericin B, compared with amphotericin B alone. Although we did find a nonsignificant benefit for addition of flucytosine to amphotericin B in studies including participants with altered levels of consciousness, we did not identify a benefit for combination therapy in restricted analyses in either resource- rich or resource-limited settings, studies conducted before or after 2004, and studies restricted to a high dose of amphotericin B and fluconazole. Conclusions. Given considerations of drug availability and toxicity, there is an important need for additional data to clarify which populations are most likely to benefit from combination therapies for human immunodeficiency virusassociated cryptococcal meningitis.

KW - Cryptococcal meningitis

KW - HIV/AIDS

KW - Induction therapy

KW - Network meta-analysis

KW - Therapeutics

UR - http://www.scopus.com/inward/record.url?scp=84978328470&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978328470&partnerID=8YFLogxK

U2 - 10.1093/ofid/ofv010

DO - 10.1093/ofid/ofv010

M3 - Article

C2 - 26034761

AN - SCOPUS:84978328470

VL - 2

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

SN - 2328-8957

IS - 1

M1 - ofv010

ER -