HIV-1 InfectionPhase 3NCT05705349
DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053)
A Phase 3 study testing DOR/ISL and BIC/FTC/TAF in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 131 sites in 21 countries.
Trial summary
This is a randomized, active-controlled, double-blind clinical study designed to evaluate the antiretroviral activity, safety, and tolerability of doravirine/islatravir (DOR/ISL [MK-8591A]) in treatment-naïve participants with human immunodeficiency virus type 1 (HIV-1) infection. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- DOR/ISL and BIC/FTC/TAF
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 537 participants
- Where
- 131 sitesin 21 countries
- Study dates
- 8 Mar 2023to 5 Aug 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Is HIV-1 positive with plasma HIV-1 RNA ≥500 copies/mL at screening
- Is naïve to antiretroviral therapy (ART) defined as having received no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection
- If female, is not a participant of childbearing potential (POCBP); or if a POCBP, is not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration
Who cannot join
- Has HIV-2 infection
- Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
- Has a diagnosis of an active AIDS-defining opportunistic infection within 30 days prior to screening
- Has active hepatitis B infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA]-positive).
- Has chronic hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid [RNA]) and lab values are consistent with cirrhosis
- Has a history of malignancy ≤5 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma
- Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality, or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate
Trial locations and contacts
131 sites in 21 countries.
131 sites in 21 countries
United States38 sites
Emory University and Grady Health System-Medicine ( Site 5690)
Atlanta, Georgia, 30308
Emory University Hospital Midtown Infectious Disease Clinic ( Site 5673)
Atlanta, Georgia, 30308
Atlanta I.D. Group ( Site 5680)
Atlanta, Georgia, 30309
Central Texas Clinical Research ( Site 5661)
Austin, Texas, 78705
St Hope Foundation ( Site 5659)
Bellaire, Texas, 77401
Be Well Medical Center ( Site 5650)
Berkley, Michigan, 48072
Pacific Oaks Medical Group ( Site 5681)
Beverly Hills, California, 90211
Atrium Health Infectious Disease Kenilworth - Charlotte ( Site 5675)
Charlotte, North Carolina, 28204
Rush University Medical Center-Infectious Disease ( Site 5671)
Chicago, Illinois, 60612
University of Illinois at Chicago-Project WISH ( Site 5685)
Chicago, Illinois, 60612
Howard Brown Health Center-Clinical Research ( Site 5665)
Chicago, Illinois, 60613
University of Cincinnati Medical Center-Infectious Diseases - Outpatient ( Site 5662)
Cincinnati, Ohio, 45267-0405
Prism Health North Texas, Oak Cliff Health Center ( Site 5660)
Dallas, Texas, 75208
North Texas Infectious Diseases Consultants, P.A ( Site 5651)
Dallas, Texas, 75246
Metro Infectious Diseases Consultants L.L.C. ( Site 5653)
Decatur, Georgia, 30033
Vivent Health ( Site 5694)
Denver, Colorado, 80246
Henry Ford Hospital ( Site 5667)
Detroit, Michigan, 48202
AXCES Research - Texas - El Paso ( Site 5692)
El Paso, Texas, 79902
Texas Centers for Infectious Disease Associates ( Site 5656)
Fort Worth, Texas, 76104
Midway Immunology and Research Center ( Site 5657)
Ft. Pierce, Florida, 34982
Regional Center for Infectious Diseases ( Site 5687)
Greensboro, North Carolina, 27401
ID Care ( Site 5676)
Hillsborough, New Jersey, 08844
KC CARE Health Center-Clinical Trials ( Site 5670)
Kansas City, Missouri, 64111
Jubilee Clinical Research ( Site 5679)
Las Vegas, Nevada, 89106
Las Vegas Research Center ( Site 5691)
Las Vegas, Nevada, 89106
DCOL Center for Clinical Research ( Site 5664)
Longview, Texas, 75605
Ruane Clinical Research Group, Inc ( Site 5658)
Los Angeles, California, 90036
Mercer University, Department of Internal Medicine ( Site 5655)
Macon, Georgia, 31201
AHF The Kinder Medical Group ( Site 5672)
Miami, Florida, 33133
AHF South Beach ( Site 5663)
Miami Beach, Florida, 33140
Columbia University Irving Medical Center-Division of Infectious Diseases ( Site 5688)
New York, New York, 10032
Saint Michael's Medical Center ( Site 5682)
Newark, New Jersey, 07102
Orlando Immunology Center ( Site 5654)
Orlando, Florida, 32803
Pueblo Family Physicians ( Site 5674)
Phoenix, Arizona, 85015
CAN Community Health - Sarasota ( Site 5668)
Sarasota, Florida, 34237
Jacobi Medical Center ( Site 5683)
The Bronx, New York, 10461
Washington Health Institute ( Site 5689)
Washington D.C., District of Columbia, 20017
Triple O Research Institute, P.A ( Site 5666)
West Palm Beach, Florida, 33407
South Africa11 sites
Josha Research ( Site 6652)
Bloemfontein, Free State, 9301
Madibeng Centre for Research ( Site 6660)
Brits, North West, 0250
Family Clinical Research Unit (Fam-Cru)-Adult Infectious Diseases ( Site 6657)
Cape Town, Western Cape, 7500
Desmond Tutu Health Foundation ( Site 6651)
Cape Town, Western Cape, 7925
Wentworth Hospital ( Site 6653)
Durban, KwaZulu-Natal, 4052
Perinatal HIV Research Unit (PHRU)-Adult Treatment and Research ( Site 6654)
Johannesburg, Gauteng, 2013
Helen Joseph Hospital-Clinical HIV Research Unit ( Site 6661)
Johannesburg, Gauteng, 2092
Ezintsha-Clinical Research Site ( Site 6656)
Johannesburg, Gauteng, 2193
Qhakaza Mbokodo Research Clinic ( Site 6659)
Ladysmith, KwaZulu-Natal, 3370
Be Part Yoluntu Centre ( Site 6650)
Paarl, Western Cape, 7626
Human Sciences Research Council-Centre for Community Based Research ( Site 6664)
Pietermaritzburg, KwaZulu-Natal, 3201
Spain11 sites
Hospital Germans Trias i Pujol-Fundació Lluita contra la Sida ( Site 6351)
Badalona, Barcelona, 08916
HOSPITAL CLÍNIC DE BARCELONA-Infection Day Hospital ( Site 6350)
Barcelona, Catalonia, 08036
Hospital Universitari Vall d'Hebron-Infectious Diseases: HIV unit ( Site 6352)
Barcelona, 08035
Hospital General Universitario de Elche-Infectius Disease ( Site 6358)
Elche, Alicante, 03202
Hospital Universitari de Bellvitge ( Site 6360)
L'Hospitalet de Llobregat,Barcelona, Catalonia, 08907
HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON-Unidad de Enfermedades Infecciosas ( Site 6353)
Madrid, Madrid, Comunidad de, 28007
Hospital Universitario Ramón y Cajal-ENFERMEDADES INFECCIOSAS ( Site 6361)
Madrid, Madrid, Comunidad de, 28034
Hospital Universitario Fundación Jiménez Díaz-Internal Medicine. Infectious disease ( Site 6357)
Madrid, 28015
Hospital Universitario 12 de Octubre ( Site 6355)
Madrid, 28041
Hospital Universitario La Paz ( Site 6354)
Madrid, 28046
Hospital Universitario Virgen de la Victoria ( Site 6359)
Málaga, 29010
France7 sites
Hôpital Avicenne ( Site 6160)
Bobigny, Île-de-France Region, 93000
Centre Hospitalier Universitaire de Nice - Hôpital l'Archet ( Site 6153)
Nice, Alpes-Maritimes, 06202
Hôpital Bichat - Claude-Bernard ( Site 6162)
Paris, 75018
Hôpital Saint Antoine ( Site 6158)
Paris, 75571
Hôpital Saint-Louis ( Site 6159)
Paris, Île-de-France Region, 75010
Pitie Salpetriere University Hospital ( Site 6156)
Paris, Île-de-France Region, 75013
Tourcoing Hospital ( Site 6150)
Tourcoing, Nord, 59200
Malaysia7 sites
Hospital Sultanah Bahiyah ( Site 7776)
Alor Star, Kedah, 05460
Hospital Selayang ( Site 7770)
Batu Caves, Selangor, 68100
Hospital Pulau Pinang ( Site 7779)
George Town, Pulau Pinang, 10450
Hospital Kuala Lumpur ( Site 7773)
Kuala Lumpur, 50586
Sarawak General Hospital ( Site 7772)
Kuching, Sarawak, 93586
University Malaya Medical Centre-Clinical Investigation Centre (CIC) ( Site 7777)
Lembah Pantai, Kuala Lumpur, 59100
Hospital Sungai Buloh ( Site 7778)
Sungai Buloh, Selangor, 47000
Chile6 sites
Biomedica Research Group-Infectology ( Site 5951)
Santiago, Region M. de Santiago, 7500710
Espacio Eme ( Site 5952)
Santiago, Region M. de Santiago, 7770086
Centro de Investigacion Clinicadela Universidad Catolica ( Site 5953)
Santiago, Region M. de Santiago, 8330034
Universidad de Chile - Hospital Clínico Universidad de Chile-Inmunologia Alergia y VIH ( Site 5950)
Santiago, Region M. de Santiago, 8380420
Clinica Universidad Catolica del Maule ( Site 5954)
Talca, Maule Region, 3465584
Hospital hernan henriquez aravena de temuco-Unidad de Investigación Clínica ( Site 5955)
Temuco, Araucania, 4781151
Argentina5 sites
Fundación IDEAA ( Site 5851)
Buenos Aires, C1405CKC
Fundación Huésped ( Site 5850)
CABA, Buenos Aires, C1427CEA
Instituto Oulton ( Site 5853)
Córdoba, X5000JJS
Instituto de Investigaciones Clínicas Mar del Plata ( Site 5854)
Mar del Plata, Buenos Aires, B7600FZO
Instituto CAICI SRL ( Site 5852)
Rosario, Santa Fe Province, S2000PBJ
Canada5 sites
Hamilton Health Sciences-Urgent Care Centre ( Site 5750)
Hamilton, Ontario, L8S 1A4
Clinique Medicale lActuel ( Site 5752)
Montreal, Quebec, H2L 4P9
McGill University Health Centre ( Site 5751)
Montreal, Quebec, H4A 3J1
Regina General Hospital ( Site 5754)
Regina, Saskatchewan, S4P 0W5
Toronto General Hospital ( Site 5753)
Toronto, Ontario, M5G 2C4
Colombia5 sites
Ciensalud Ips S A S ( Site 6050)
Barranquilla, Atlántico, 08001
Clinica de la Costa S.A.S. ( Site 6055)
Barranquilla, Atlántico, 080020
Hospital Universitario San Ignacio-Infectious ( Site 6053)
Bogotá, Bogota D.C., 110231
Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 6051)
Bogotá, Bogota D.C., 111321
Fundación Valle del Lili ( Site 6052)
Cali, Valle del Cauca Department, 760032
Germany5 sites
Universitätsklinikum Bonn-Immunologie ( Site 6250)
Bonn, North Rhine-Westphalia, 53127
Universitaetsklinikum Freiburg ( Site 6256)
Freiburg, Brandenburg, 79106
ICH Study Center GmbH & Co. KG ( Site 6259)
Hamburg, 20146
Universitaetsklinikum Hamburg-Eppendorf-Infektiologie ( Site 6260)
Hamburg, 20246
Klinikum der Ludwig-Maximilians-Universitaet Muenchen-Medizinische Klinik und Poliklinik IV, Sektio
München, Bavaria, 80336
United Kingdom5 sites
Southmead Hospital ( Site 7952)
Bristol, Bristol, City of, BS10 5NB
Royal London Hospital ( Site 7951)
London, England, E1 1BB
King's College Hospital ( Site 7950)
London, London, City of, SE5 9RL
The Mortimer Market Centre for Sexual Health and HIV Research ( Site 7954)
London, London, City of, WC1E 6JB
The Hathersage Centre ( Site 7953)
Manchester, England, M13 0FH
Israel4 sites
Rambam Health Care Campus-Institute of Allergy, Clinical Immunology, ( Site 6751)
Haifa, 3109601
Hadassah Medical Center-Infecious Disease ( Site 6752)
Jerusalem, 9120
Sheba Medical Center-HIV unit ( Site 6753)
Ramat Gan, 5262100
Sourasky Medical Center ( Site 6754)
Tel Aviv, 6423906
Japan4 sites
National Hospital Organization Nagoya Medical Center ( Site 6953)
Nagoya, Aichi-ken, 460-0001
National Hospital Organization Osaka National Hospital ( Site 6952)
Osaka, 540-0006
Tokyo Medical University Hospital ( Site 6954)
Shinjuku-ku, Tokyo, 160-0023
Center Hospital of the National Center for Global Health and Medicine ( Site 6951)
Shinjyuku-ku, Tokyo, 162-8655
Guatemala3 sites
CLINIPHARM ( Site 8352)
Guatemala City, 01001
Clínica Médica Especializada en Pediatría e Infectología Pediátrica - Dr. Mario Melgar ( Site 8350)
Guatemala City, 01009
CELAN,S.A ( Site 8351)
Guatemala City, 01010
Kenya3 sites
KEMRI-CMR-RCTP ( Site 8650)
Kisumu, 40100
CCR KEMRI (Center for Clinical Research) ( Site 8652)
Nairobi, Nairobi City, 00200
PHRD KEMRI (Partners in Health Research & Development) ( Site 8651)
Nairobi, Nairobi City, 00202
Puerto Rico3 sites
Ponce Medical School Foundation Inc. ( Site 7452)
Ponce, 00716
Clinical Research Puerto Rico ( Site 7450)
San Juan, 00909
HOPE Clinical Research ( Site 7451)
San Juan, 00909
Thailand3 sites
HIV Netherlands Australia Thailand Research Collaboration ( Site 7851)
Bangkok, Bangkok, 10330
Faculty of Medicine Siriraj Hospital-Preventive and social ( Site 7850)
Bangkok, Bangkok, 10700
Research Institute for Health Sciences-Research Institute for Health Sciences Building 1 ( Site 7852
Chiang Mai, 50200
Switzerland2 sites
University Hospital Basel-Infectiology ( Site 8151)
Basel, Canton of Basel-City, 4031
Hôpitaux Universitaires de Genève (HUG)-Infectious Disease Department ( Site 8150)
Geneva, Canton of Geneva, 1205
Turkey (Türkiye)2 sites
Hacettepe Universite Hastaneleri ( Site 7650)
Altindağ, Ankara, 06230
Ankara Bilkent Şehir Hastanesi-Infectious Disease and Clinical Microbiology ( Site 7659)
Ankara, 06800
Dominican Republic1 site
Instituto Dermatológico y Cirugía de Piel "Dr. Huberto Bogaert Díaz" ( Site 8250)
Santo Domingo de Guzman, Santo Domingo Province, 10305
Mexico1 site
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 7251)
Mexico City, Mexico City, 14080
About this study
Official title: A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in HIV-1 Infected Treatment-Naïve Participants
This is a randomized, active-controlled, double-blind clinical study designed to evaluate the antiretroviral activity, safety, and tolerability of doravirine/islatravir (DOR/ISL [MK-8591A]) in treatment-naïve participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that DOR/ISL is non-inferior to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48.
- Conditions
- HIV-1 Infection
- Being tested
- DOR/ISL, BIC/FTC/TAF, Placebo to DOR/ISL, Placebo to BIC/FTC/TAF
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DOR/ISLDrug
Also called MK-8591A
Fixed dose combination tablet containing DOR/ISL 100 mg/0.25 mg taken by mouth.
BIC/FTC/TAFDrug
Fixed dose combination tablet containing BIC/FTC/TAF 50 mg/200 mg/25 mg taken by mouth.
Placebo to DOR/ISLDrug
Placebo tablet matched to DOR/ISL tablet taken by mouth.
Placebo to BIC/FTC/TAFDrug
Placebo tablet matched to BIC/FTC/TAF tablet taken by mouth.
| Study group | Role | What they receive |
|---|---|---|
| DOR/ISL | Experimental | Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 144 weeks. Receives: Drug: DOR/ISL; Drug: Placebo to BIC/FTC/TAF |
| BIC/FTC/TAF | Active comparator | Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 144 weeks. Receives: Drug: BIC/FTC/TAF; Drug: Placebo to DOR/ISL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL at Week 48
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay with a lower limit of detection of <50 copies/mL.
Measured: Week 48
Percentage of participants experiencing ≥1 adverse event (AE) through Week 48
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measured: Up to 48 weeks
Percentage of participants discontinuing from study treatment due to an AE through Week 48
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measured: Up to 48 weeks
Secondary outcomes (14)
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of <50 copies/mL.
Measured: Week 96
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of <50 copies/mL.
Measured: Week 144
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of <50 copies/mL.
Measured: Week 48
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of <50 copies/mL.
Measured: Week 96
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144
Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of <50 copies/mL.
Measured: Week 144
Change from baseline in cluster of differentiation 4+ (CD4+) T-cells at Week 48
CD4+ T-cells are quantified with a T and B lymphocyte and natural killer cell (TBNK) panel.
Measured: Baseline (Day 1) and Week 48
Change from baseline in CD4+ T-cells at Week 96
CD4+ T-cells are quantified with a TBNK panel.
Measured: Baseline (Day 1) and Week 96
Change from baseline in CD4+ T-cells at Week 144
CD4+ T-cells are quantified with a TBNK panel.
Measured: Baseline (Day 1) and Week 144
Incidence of viral drug resistance
Plasma samples will be collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and viral susceptibility as applicable during the study.
Measured: Up to 96 weeks
Change from baseline in body weight at Week 48
Body weight will be collected throughout the study.
Measured: Baseline (Day 1) and Week 48
Change from baseline in body weight at Week 96
Body weight will be collected throughout the study.
Measured: Baseline (Day 1) and Week 96
Change from baseline in body weight at Week 144
Body weight will be collected throughout the study.
Measured: Baseline (Day 1) and Week 144
Percentage of participants experiencing ≥1 AE through Week 144
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measured: Up to 144 weeks
Percentage of participants discontinuing from study treatment due to an AE through Week 144
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Measured: Up to 144 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start8 Mar 2023
- Primary completion13 Oct 2025
- Study completion5 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 537 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05705349
- Sponsor's protocol ID
- 8591A-053
- Other IDs
- 2022-502099-22-00, jRCT2031220720, U1111-1283-2516
- Status last verified
- Sep 2026
- First submitted
- 20 Jan 2023
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Rockstroh JK, Kassim S, Paredes R, Bettacchi C, Sinclair G, Avihingsanon A, Mugo N, Molina JM, Crabtree Ramirez B, Gatanaga H, Xu Y, Klopfer SO, Diamond TL, Vesnesky M, Stamm LM, Fox MC, Pisculli ML. Fixed-dose daily doravirine (100 mg) with islatravir (0.25 mg) versus bictegravir, emtricitabine, and tenofovir alafenamide for initial HIV-1 therapy: 48-week results of a phase 3, randomised, controlled, double-blind, non-inferiority trial. Lancet HIV. 2026 Jul;13(7):e440-e451. doi: 10.1016/S2352-3018(26)00033-0. Epub 2026 Feb 25.
PubMed 41763226