Evidence map›Paper›PMID 36707795›Full record

Trial reportMalaria journal2023

Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi.

Wongani Nyangulu, Randy G Mungwira, Titus H Divala, Nginache Nampota-Nkomba, Osward M Nyirenda, Andrea G Buchwald, Jernelle Miller, Dominique E Earland, Matthew Adams, Christopher V Plowe and 7 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Malaria journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 27% 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

1 citing paper in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.

  1. Pooled it
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

17 authors at 6 institutions in 2 countries.

Wongani NyanguluDignitas International, Zomba, Malawi.
Randy G MungwiraBlantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Titus H DivalaDignitas International, Zomba, Malawi.
Nginache Nampota-NkombaBlantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Osward M NyirendaBlantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Andrea G BuchwaldCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA.
Jernelle MillerCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA.
Dominique E EarlandCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA.
Matthew AdamsCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA.
Christopher V PloweCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA.
Terrie E TaylorBlantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Jane E MallewaDepartment of Medicine, Kamuzu University of Health Sciences, Blantyre, Malawi.
Joep J van OosterhoutDignitas International, Zomba, Malawi.
Sunil ParikhYale School of Public Health, New Haven, USA.
Matthew B LaurensCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA.
Miriam K LauferCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., Baltimore, MD, 21201, USA. mlaufer@som.umaryland.edu.
TSCQ Study Team
University of Maryland, Baltimore · USKamuzu University of Health SciencesDignitas International · MWKamuzu Central Hospital · MWMichigan State University · USUniversity of California, Los Angeles · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
The role of monocytes in the pathology of severe malaria.U19AI089683 · NIAID · MICHIGAN STATE UNIVERSITY · PI MATENGENI, ALFRED · 2010 to 2023
$21.4M
UMB Postbaccalaureate Research Education ProgramR25GM113262 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI ANTALIS, TONI M, CAREY, GREGORY B · 2016 to 2025
$3.2M
National Institute of Allergy and Infectious Diseases U01AI089683NCATS NIH HHS UL1 TR001863NIAID NIH HHS U19 AI089683NIGMS NIH HHS R25 GM113262NIGMS NIH HHS R25GM113262
6 · The paper itself

Abstract

backgroundWhen people with human immunodeficiency virus (HIV) infection (PWH) develop malaria, they are at risk of poor anti-malarial treatment efficacy resulting from impairment in the immune response and/or drug-drug interactions that alter anti-malarial metabolism. The therapeutic efficacy of artemether-lumefantrine was evaluated in a cohort of PWH on antiretroviral therapy (ART) and included measurement of day 7 lumefantrine levels in a subset to evaluate for associations between lumefantrine exposure and treatment response.

methodsAdults living with HIV (≥ 18 years), on ART for ≥ 6 months with undetectable HIV RNA viral load and CD4 count ≥ 250/mm

results411 malaria episodes were observed among 186 participants over 5 years. The unadjusted ACPR rate was 81% (95% CI 77-86). However, after PCR correction to exclude new infections, ACPR rate was 94% (95% CI 92-97). Increasing age and living in Ndirande were associated with decreased hazard of treatment failure. In this population of adults with HIV on ART, 54% (51/94) had levels below a previously defined optimal day 7 lumefantrine level of 200 ng/ml. This occurred more commonly among participants who were receiving an efavirenz-based ART compared to other ART regimens (OR 5.09 [95% CI 1.52-7.9]). Participants who experienced treatment failure had lower day 7 median lumefantrine levels (91 ng/ml [95% CI 48-231]) than participants who experienced ACPR (190 ng/ml [95% CI 101-378], p-value < 0.008).

conclusionRecurrent malaria infections are frequent in this population of PWH on ART. The PCR-adjusted efficacy of AL meets the WHO criteria for acceptable treatment efficacy. Nevertheless, lumefantrine levels tend to be low in this population, particularly in those on efavirenz-based regimens, with lower concentrations associated with more frequent malaria infections following treatment. These results highlight the importance of understanding drug-drug interactions when diseases commonly co-occur.

Indexed as

AntimalarialsArtemisininsHIV InfectionsMalariaMalaria, FalciparumAdultAlkynesArtemetherArtemether, Lumefantrine Drug CombinationBenzoxazinesCyclopropanesDrug CombinationsEthanolaminesFluorenesHumansLumefantrineAlkynesAntimalarialsArtemetherArtemether, Lumefantrine Drug CombinationArtemisininsBenzoxazinesCyclopropanesDrug CombinationsefavirenzEthanolaminesFluorenesLumefantrine

Identifiers

PMID36707795
PMCPMC9881508
OpenAlexW4318220697

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.