Evidence map›Paper›PMID 31345462›Full record

Trial reportThe Lancet. Infectious diseases2019

Adjunctive sertraline for HIV-associated cryptococcal meningitis: a randomised, placebo-controlled, double-blind phase 3 trial.

Joshua Rhein, Kathy Huppler Hullsiek, Lillian Tugume, Edwin Nuwagira, Edward Mpoza, Emily E Evans, Reuben Kiggundu, Katelyn A Pastick, Kenneth Ssebambulidde, Andrew Akampurira and 9 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01802385 (Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis), which is not on this map. Cited by 88 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 5 pooled it
11.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01802385 phase3completednot on this map

Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis

TypeinterventionalSponsorUniversity of MinnesotaRan2015 to 2017Enrolled460ConditionsCryptococcal Meningitis, Fungal MeningitisArmsSertraline
3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 5 syntheses or guidelines pooled it, 123 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Trial
  7. Trial
  8. Trial
  9. Trial
  10. Review
  11. Article
  12. Evaluating Desirability of Outcome Ranking (DOOR) and Win Ratio for Hierarchical Composite Endpoints in Cryptococcal Meningitis Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
    Article
  13. Article
  14. Article
  15. A review of the current anti-New microbes and new infections · 2026
    Review
  16. Article
  17. Article
  18. Drug Discovery and Repurposing forJournal of fungi (Basel, Switzerland) · 2025
    Review
  19. Review
  20. Review

28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 2 countries.

Joshua RheinDepartment of Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA; Infectious Diseases Institute, Makerere University, Kampala, Uganda. Electronic address: joshua.rhein@gmail.com.
Kathy Huppler HullsiekSchool of Public Health, Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
Lillian TugumeInfectious Diseases Institute, Makerere University, Kampala, Uganda.
Edwin NuwagiraMbarara University of Science and Technology, Mbarara, Uganda.
Edward MpozaInfectious Diseases Institute, Makerere University, Kampala, Uganda.
Emily E EvansMbarara University of Science and Technology, Mbarara, Uganda.
Reuben KiggunduInfectious Diseases Institute, Makerere University, Kampala, Uganda.
Katelyn A PastickDepartment of Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA; Infectious Diseases Institute, Makerere University, Kampala, Uganda.
Kenneth SsebambuliddeInfectious Diseases Institute, Makerere University, Kampala, Uganda.
Andrew AkampuriraInfectious Diseases Institute, Makerere University, Kampala, Uganda.
Darlisha A WilliamsDepartment of Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA; Infectious Diseases Institute, Makerere University, Kampala, Uganda.
Ananta S BangdiwalaSchool of Public Health, Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
Mahsa AbassiDepartment of Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA; Infectious Diseases Institute, Makerere University, Kampala, Uganda.
Abdu K MusubireInfectious Diseases Institute, Makerere University, Kampala, Uganda.
Melanie R NicolDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
Conrad MuzooraMbarara University of Science and Technology, Mbarara, Uganda.
David B MeyaDepartment of Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA; Infectious Diseases Institute, Makerere University, Kampala, Uganda; School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
David R BoulwareDepartment of Medicine, Medical School, University of Minnesota, Minneapolis, MN, USA.
ASTRO-CM team
Infectious Diseases Institute · UGMbarara University of Science and Technology · UGUniversity of Minnesota · USUniversity of Minnesota Medical Center · US

Funding

Improving Diagnostics and Neurocognitive Outcomes in HIV/AIDS-related MeningitisR01NS086312 · NINDS · UNIVERSITY OF MINNESOTA · PI David R Boulware, David Bisagaya Meya · 2013 to 2026
$8.3M
Infectious Disease Training in Clinical InvestigationT32AI055433 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI David R Boulware · 2003 to 2026
$6.1M
Northern/Pacific Universities Global Health Research Training ConsortiumR25TW009345 · FIC · UNIVERSITY OF WASHINGTON · PI KOLARS, JOSEPH C., NERURKAR, VIVEK RAMCHANDRA · 2012 to 2016
$5.9M
Evaluating Antiretroviral Pharmacology in the Female Genital Tract to Optimize HIV PreventionK08AI134262 · NIAID · UNIVERSITY OF MINNESOTA · PI NICOL, MELANIE RAE · 2018 to 2022
$847k
Improving Outcomes of HIV-Associated Cryptococcosis in Resource-Limited SettingsK01TW010268 · FIC · UNIVERSITY OF MINNESOTA · PI RHEIN, JOSHUA R · 2016 to 2020
$703k
Medical Student Summer Research Program in Infection and ImmunityT35AI118620 · NIAID · UNIVERSITY OF MINNESOTA · PI MUELLER, DANIEL L · 2015 to 2025
$351k
FIC NIH HHS K01 TW010268FIC NIH HHS R25 TW009345Medical Research Council MR/M007413/1NIAID NIH HHS K08 AI134262NIAID NIH HHS L30 AI140310NIAID NIH HHS T32 AI055433NIAID NIH HHS T35 AI118620NINDS NIH HHS R01 NS086312Wellcome Trust
6 · The paper itself

Abstract

backgroundIdentifying new antifungals for cryptococcal meningitis is a priority given the inadequacy of current therapy. Sertraline has previously shown in vitro and in vivo activity against cryptococcus. We aimed to assess the efficacy and cost-effectiveness of adjunctive sertraline in adults with HIV-associated cryptococcal meningitis compared with placebo.

methodsIn this double-blind, randomised, placebo-controlled trial, we recruited HIV-positive adults with cryptococcal meningitis from two hospitals in Uganda. Participants were randomly assigned (1:1) to receive standard therapy with 7-14 days of intravenous amphotericin B (0·7-1·0 mg/kg per day) and oral fluconazole (starting at 800 mg/day) with either adjunctive sertraline or placebo. Sertraline was administered orally or via nasogastric tube at a dose of 400 mg/day for 2 weeks, followed by 200 mg/day for 12 weeks, then tapered off over 3 weeks. The primary endpoint was 18-week survival, analysed by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT01802385.

findingsBetween March 9, 2015, and May 29, 2017, we screened 842 patients with suspected meningitis and enrolled 460 of a planned 550 participants, at which point the trial was stopped for futility. Three patients in the sertraline group and three patients in the placebo group were lost to follow-up and therefore discontinued before study end. At 18 weeks, 120 (52%) of 229 patients in the sertraline group and 106 (46%) of 231 patients in the placebo group had died (hazard ratio 1·21, 95% CI 0·93-1·57; p=0·15). The fungal clearance rate from cerebrospinal fluid was similar between groups (0·43 -log

interpretationSertraline did not reduce mortality and should not be used to treat patients with HIV-associated cryptococcal meningitis. The reasons for sertraline inactivity appear to be multifactorial and might be associated with insufficient duration of therapeutic sertraline concentrations.

fundingNational Institutes of Health and Medical Research Council, Wellcome Trust.

Indexed as

Adjuvants, PharmaceuticAdultAIDS-Related Opportunistic InfectionsAmphotericin BAntifungal AgentsCost-Benefit AnalysisCryptococcusDouble-Blind MethodFemaleFluconazoleHIV InfectionsHumansMaleMeningitis, CryptococcalSertralineTreatment OutcomeAdjuvants, PharmaceuticAmphotericin BAntifungal AgentsFluconazoleSertraline

Identifiers

PMID31345462
PMCPMC7041360
OpenAlexW2963973517

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.