Doravirine/Islatravir (DOR/ISL) in Heavily Treatment-Experienced (HTE) Participants for Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-019)
HIV-1 Infection
About this trial
This is an interventional treatment trial for HIV-1 Infection
Eligibility Criteria
Inclusion Criteria:
- Is HIV-1 positive.
- Has been receiving the same baseline ART for ≥3 months prior to signing the Informed Consent Form/Assent Form.
- Weighs ≥35 kg.
- Has at least triple-class resistance (must include nucleoside reverse transcriptase inhibitor [NRTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], and resistance to either protease inhibitor (PI) or integrase strand transfer inhibitor (InSTI), based on central laboratory-based resistance or proviral DNA resistance testing at the Screening Visit, or historical resistance testing within 12 months of screening.
- Has ≤2 fully active antiretroviral drugs remaining among all antiretroviral classes that can be effectively combined to form a viable regimen based on resistance, tolerability, safety, drug access, or acceptability to participant.
- If female, is not pregnant or breastfeeding, and is: 1) not a woman of childbearing potential (WOCBP); 2) a WOCBP and uses an acceptable method of contraception/is abstinent; or 3) a WOCBP and has a negative pregnancy test within 24 hours of the first dose of study medication.
Exclusion Criteria:
- Has HIV type 2 (HIV-2) infection.
- Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator.
- Has hepatitis B virus (HBV) co-infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive) and is not currently being treated for HBV.
- Has a history or current evidence of any condition, therapy (including active TB co-infection), laboratory abnormality or other circumstance (including drug or alcohol abuse or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with study participation for the full study duration.
- Is taking or is anticipated to require any of the prohibited therapies from the Screening Visit and throughout the study treatment period.
- Is taking DOR as part of his/her current failing antiretroviral regimen.
- Is taking efavirenz (EFV), etravirine, or nevirapine.
- Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from the Screening Visit through the study treatment period.
- Is female and is expecting to conceive or donate eggs at any time during the study.
Sites / Locations
- University of Alabama at Birmingham 1917 Research Clinic ( Site 4031)
- Men's Health Foundation ( Site 4018)
- Palmtree Clinical Research, Inc. ( Site 4016)
- Yale School of Medicine ( Site 4007)
- Georgetown University Hospital ( Site 4015)
- The Kinder Medical Group ( Site 4014)
- Orlando Immunology Center ( Site 4012)
- Triple O Research Institute, P.A. ( Site 4020)
- Chatham County Health Department ( Site 4029)
- Howard Brown Health Center ( Site 4006)
- Northstar Healthcare ( Site 4004)
- University of Maryland ( Site 4023)
- The University of Mississippi Medical Center ( Site 4036)
- Saint Michael's Medical Center-Research - Infectious Disease ( Site 4035)
- Icahn School of Medicine at Mount Sinai ( Site 4000)
- University of North Carolina at Chapel Hill ( Site 4026)
- Saint Hope Foundation, Inc. ( Site 4034)
- North Texas Infectious Diseases Consultants, PA ( Site 4005)
- Dr. Peter Shalit, MD ( Site 4002)
- Holdsworth House Medical Practice ( Site 5300)
- St Vincent's Hospital ( Site 5309)
- Holdsworth House Medical Practice - Brisbane ( Site 5312)
- Monash Health-Monash Medical Centre ( Site 5313)
- The Alfred Hospital ( Site 5304)
- Vancouver ID Research and Care Centre Society ( Site 4100)
- Hamilton Health Sciences ( Site 4115)
- Ottawa Hospital Research Institute ( Site 4111)
- Toronto General Hospital - University Health Network ( Site 4105)
- McGill University Health Center - Research Institute-CVIS Clinical Research Unit ( Site 4102)
- Hospital Dr. Hernan Henriquez Aravena ( Site 4405)
- Fundacion Arriaran ( Site 4401)
- Centro Cardiovascular Cardiosur ( Site 4407)
- Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 4306)
- Fundacion Valle del Lili ( Site 4301)
- Hopital Edouard Herriot ( Site 4726)
- A.P.H. Paris. Hopital Bichat Claude Bernard ( Site 4724)
- CHU de Nice Hopital Archet 1 ( Site 4703)
- Hopital Europeen Marseille ( Site 4717)
- CHU de Bordeaux- Hopital Saint Andre ( Site 4715)
- CHU de Rouen ( Site 4705)
- CHU de Montpellier - Hopital Saint-Eloi ( Site 4721)
- Centre Hospitalier de Tourcoing ( Site 4700)
- Hopital Avicenne ( Site 4702)
- Hopital Hotel Dieu [Paris, France] ( Site 4723)
- A.P.H. Paris, Hopital Saint Louis ( Site 4714)
- Medizinische Hochschule Hannover ( Site 4612)
- Universitaetsklinikum Bonn ( Site 4600)
- Universitaetsklinikum Essen ( Site 4607)
- ZIBP-Zentrum fur Infektiologie Berlin Prenzlauer Berg GmbH ( Site 4603)
- EPIMED GmbH ( Site 4608)
- ICH Study Center GmbH & Co.KG ( Site 4609)
- Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 5004)
- Ospedale San Gerardo ASST Monza ( Site 5012)
- Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico ( Site 5001)
- Universita' Vita Salute. Ospedale San Raffaele ( Site 5002)
- Azienda Ospedaliera San Paolo ( Site 5003)
- ASST Fatebenefratelli-Ospedale Sacco ( Site 5000)
- IRCCS Policlinico San Matteo ( Site 5010)
- Istituto Nazionale per Le Malattie Infettive Lazzaro Spallanzani ( Site 5005)
- Policlinico Gemelli Instituto di Clinica Chirurgica ( Site 5006)
- Center Hospital of the National Center for Global Health and Medicine ( Site 5401)
- Pusan National University Hospital ( Site 5503)
- Severance Hospital Yonsei University Health System ( Site 5500)
- The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 5502)
- INMENSA ( Site 4506)
- Via Libre ( Site 4500)
- Policlinico Universidad Nacional Mayor de San Marcos ( Site 4501)
- Hospital de Nossa Senhora da Oliveira- EPE ( Site 4905)
- Hospital Dr. Fernando Fonseca, EPE - Amadora/Sintra ( Site 4902)
- Centro Hospitalar de Lisboa Norte Hospital de Santa Maria ( Site 4913)
- Hospital Geral de Santo Antonio ( Site 4908)
- Centro Hospitalar de Sao Joao. EPE - Hospital de Sao Joao ( Site 4907)
- HOPE Clinical Research ( Site 5700)
- Saint Petersburg Center for Prophylactic of AIDS and Inf. Diseases ( Site 5101)
- Infectious Clinical Hospital #2 ( Site 5114)
- Gbuz Samarskiy Oblastnoy Klinicheskiy Tsentr Profilaktiki I Bor'by So Spid ( Site 5113)
- FGU Republican Clinical Infectious Hospital of Roszdrav ( Site 5100)
- Smolensk Center On Aids And Infectious Diseases Prophylaxis ( Site 5115)
- Regional Center for Prevent. and Control of AIDS and Inf. Diseases ( Site 5106)
- Republican Clinical Hospital of Infectious Diseases n. a. A.F.Agafonov ( Site 5104)
- FARMOVS ( Site 4805)
- Wits Clinical HIV Research Unit ( Site 4804)
- Ezintsha ( Site 4806)
- King Edward Hospital ( Site 4802)
- Hospital Universitari Germans Trias i Pujol ( Site 5600)
- Hospital Clinic i Provincial ( Site 5601)
- Hospital Santa Lucia ( Site 5603)
- Hospital Universitario La Paz ( Site 5604)
- Dnipropetrovsk Regional Center of Socially Significant Diseases ( Site 5619)
- Regional Clinical Infectious Hospital ( Site 5614)
- Kherson City Clinical Hospital n.a. Y.Y. Karabelesh ( Site 5620)
- Institute of Epidemiology and Infect Diseases of the NAMS of Ukraine ( Site 5615)
- Mykolaiv center of paliative assistance and integrated services ( Site 5621)
- MNE Odesa Regional Center of Socially Significant Diseases ( Site 5611)
- MI Vinnytsia Regional Center of AIDS Prevention and Care ( Site 5618)
- Kyiv City Clinical Hospital 5 ( Site 5616)
- Royal Free Hospital ( Site 5202)
- Western General Hospital ( Site 5201)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Placebo Comparator
ISL + ART
DOR + ART
DOR/ISL + ART
Placebo + ART
HTE participants with HIV-1 infection take ISL 0.75 mg once daily (QD) in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL fixed dose combination (FDC) QD + OBT from Day 8 to Week 97.
HTE participants with HIV-1 infection take DOR 100 mg QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.
HTE participants with HIV-1 infection take 100 mg DOR/0.75 mg ISL FDC QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.
HTE participants with HIV-1 infection take placebo QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.