Evidence map›Paper›PMID 30596666›Full record

Trial reportPloS one2018

Discontinuing cotrimoxazole preventive therapy in HIV-infected adults who are stable on antiretroviral treatment in Uganda (COSTOP): A randomised placebo controlled trial.

Zacchaeus Anywaine, Jonathan Levin, Ronnie Kasirye, Joseph Kayiira Lutaakome, Andrew Abaasa, Andrew Nunn, Heiner Grosskurth, Paula Munderi, COSTOP research team

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 22% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 23 citations in OpenAlex.

  1. Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Zacchaeus AnywaineMedical Research Council / Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.ORCID 0000-0001-5771-5515
Jonathan LevinSchool of Public Health, University of Witwatersrand, Johannesburg, South Africa.
Ronnie KasiryeMedical Research Council / Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Joseph Kayiira LutaakomeMedical Research Council / Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Andrew AbaasaMedical Research Council / Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Andrew NunnMRC Clinical Trials Unit at University College London, London, United Kingdom.
Heiner GrosskurthDepartment of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Paula MunderiMedical Research Council / Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
COSTOP research team
Uganda Virus Research Institute · UGLondon School of Hygiene & Tropical Medicine · GBMRC Clinical Trials Unit at UCL · GBUniversity of the Witwatersrand · ZA

Funding

Int'l Traineeships in AIDS Prevention Studies (ITAPS)R25MH064712 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LINDAN, CHRISTINA P · 2002 to 2018
$3.4M
Medical Research Council MC_EX_UU_G0902150Medical Research Council MC_UP_A910_1026Medical Research Council MC_UU_12023/27Medical Research Council MR/K012126/1NIMH NIH HHS R25 MH064712
6 · The paper itself

Abstract

backgroundCotrimoxazole (CTX) preventive therapy (CPT) reduces opportunistic infections and malaria in HIV-infected patients. In Africa, policies on sustained CPT during antiretroviral therapy (ART) differ between countries. We assessed the safety of discontinuing CPT in stable patients on ART in Uganda.

methodsCOSTOP was a double-blind placebo-controlled trial. Patients aged ≥18 years, on CPT, and stable on ART (CD4 counts ≥250 cells/μL); were randomised to daily oral placebo (PLC group) or cotrimoxazole 960 mg/tablet (CTX group). Co-primary outcomes were: (i) time to first cotrimoxazole-preventable infection, with non- inferiority of PLC defined as the upper one-sided 95% confidence limit of the adjusted hazard ratio(aHR) ≤1.25; and (ii) time to first grade 3/4 haematological adverse event.

findings2180 subjects (1091 PLC; 1089 CTX) were enrolled. 932 PLC and 943 CTX completed the trial after 12 months minimum follow up. Ninety-eight participants (59 PLC; 39 CTX) experienced 120 cotrimoxazole- preventable events, mainly bacterial pneumonia (72 events, 4 deaths PLC); (48 events, 2 deaths CTX). The aHR for time to first event was 1.57 (upper one-sided 95% confidence limit 2.21) in per protocol population (similar results in ITT population). 551 participants (318 CTX; 233 PLC) experienced 1043 haematological adverse events (616 CTX; 427 PLC). Time to the first adverse event, mainly neutropenia, was shorter in the CTX group (aHR 0.70 95%CI 0.59-0.82; log-rank χ2 = 18.08; P<0.0001). 362 (276 PLC, 86 CTX) participants experienced at least one episode of confirmed clinical malaria (P<0.0001).

interpretationIn ART stable patients with CD4 counts ≥250 cells/μL, continued CPT significantly reduces risk of severe bacterial infections and protects against malaria, while discontinuing CPT reduces haematological adverse events.

Indexed as

AdultAnti-HIV AgentsFemaleHIV InfectionsHumansMaleMiddle AgedOpportunistic InfectionsPlacebosSafetyTrimethoprim, Sulfamethoxazole Drug CombinationUgandaWithholding TreatmentAnti-HIV AgentsPlacebosTrimethoprim, Sulfamethoxazole Drug Combination

Identifiers

PMID30596666
PMCPMC6312229
OpenAlexW2908033759

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

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.