The goal of this study is to learn what happens to doravirine (DOR) and islatravir (ISL) in a healthy lactating female's body over time. Researchers want to learn if DOR and ISL are in breast milk.

Start Date26 Sep 2025

Sponsor / Collaborator

Merck Sharp & Dohme LLC

NCT06719570

/ CompletedPhase 1

An Open-Label Study to Evaluate the Effect of a High-Fat Meal on the Pharmacokinetics of Doravirine/Islatravir (100 mg/0.25 mg) Fixed-dose Combination Tablet and to Compare the Pharmacokinetics of Doravirine/Islatravir to Doravirine and Islatravir Single Entities in Healthy Adult Participants

The purpose of this study is to learn what happens to MK-8591A in a person's body over time. Researchers will compare what happens to MK-8591A in the body when it is given with and without food.

Start Date23 Jan 2024

Sponsor / Collaborator

Merck Sharp & Dohme LLC

NCT05766501

/ Active, not recruitingPhase 3

A Phase 3 Open-label Clinical Study of Doravirine/Islatravir (DOR/ISL [100 mg/0.25 mg]) Once Daily for the Treatment of HIV-1 Infection in Participants Who Previously Received DOR/ISL (100 mg/0.75 mg) QD in a Phase 3 Clinical Study

The purpose of this study is to evaluate the safety and tolerability of DOR/ISL in adult participants with HIV-1 who had been previously treated with DOR/ISL in earlier clinical studies. There are no formal hypotheses to be tested in this study.

Start Date17 Mar 2023

Sponsor / Collaborator

Merck Sharp & Dohme LLC

100 Clinical Results associated with Doravirine/Islatravir

100 Translational Medicine associated with Doravirine/Islatravir

100 Patents (Medical) associated with Doravirine/Islatravir

Literatures (Medical) associated with Doravirine/Islatravir

01 Jul 2026·Lancet HIV

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

Article

Author: Diamond, Tracy L ; Fox, Michelle C ; Vesnesky, Mary ; Avihingsanon, Anchalee ; Paredes, Roger ; Sinclair, Gary ; Klopfer, Stephanie O ; Gatanaga, Hiroyuki ; Pisculli, Mary L ; Rockstroh, Jürgen K ; Bettacchi, Christopher ; Kassim, Sheetal ; Crabtree Ramírez, Brenda ; Molina, Jean-Michel ; Stamm, Luisa M ; Mugo, Nelly ; Xu, Yayun

BACKGROUND:

Doravirine and islatravir is a two-drug regimen being investigated for the treatment of HIV-1. This study evaluated efficacy and safety of once daily doravirine and islatravir versus bictegravir, emtricitabine, and tenofovir alafenamide in adults with HIV-1 who were treatment-naive.

METHODS:

MK-8591A-053 is a phase 3, randomised, double-blind, active-controlled, non-inferiority study being done at 116 research, community, and hospital-based clinics across 20 countries. Adults aged at least 18 years with HIV-1 RNA of 500 copies per mL or more never previously treated for HIV-1 were randomly assigned (1:1), stratified by screening HIV-1 RNA viral load and CD4-cell count, to received either doravirine (100 mg) and islatravir (0·25 mg) or bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) orally once daily. The primary endpoint was percentage of participants with HIV-1 RNA less than 50 copies per mL at week 48 (FDA snapshot; prespecified non-inferiority margin -10%). Participants who received at least one dose of study intervention were analysed for safety. This trial is ongoing and is registered with ClinicalTrials.govNCT05705349.

FINDINGS:

We screened 756 participants for eligibility between March 8, 2023, and Oct 11, 2024. 269 participants were treated with doravirine-islatravir and 267 with bictegravir-emtricitabine-tenofovir. The last study visit for this analysis occurred on Oct 13, 2025. Median age was 32 years (IQR 26-40), 134 (25%) participants were assigned female at birth, 225 (42%) were White, 92 (17%) had CD4 counts less than 200 cells per μL, 197 (37%) had an HIV-1 RNA greater than 100 000 copies per mL, and 314 (59%) had pre-existing resistance-associated mutations. At week 48, doravirine-islatravir was non-inferior to bictegravir-emtricitabine-tenofovir: 247 (91·8%) of 269 versus 242 (90·6%) of 267 had HIV-1 RNA less than 50 copies per mL (estimated difference 1·2%, 95% CI -3·7 to 6·2). Mean increase in CD4 count was 218 cells per μL in the doravirine-islatravir group and 226 cells per μL in the bictegravir-emtricitabine-tenofovir group (estimated difference -6·8, 95% CI -35·8 to 22·2). Two participants in the doravirine-islatravir group and one in the bictegravir-emtricitabine-tenofovir group with pretreatment HIV-1 RNA greater than 1 million copies per mL and CD4 counts less than 200 cells per μL acquired treatment-emergent mutations. Phenotypic analysis revealed resistance to doravirine in two participants treated with doravirine-islatravir. 38 (14%) of 269 participants in the doravirine-islatravir group and 48 (18%) of 267 in the bictegravir-emtricitabine-tenofovir group had treatment-related adverse events: the most common were increased weight (7, 3%), headache (6, 2%), and dizziness (5, 2%) in the doravirine-islatravir group and increased weight (9, 3%), headache (9, 3%), and decreased estimated glomerular filtration rate (8, 3%) in the bictegravir-emtricitabine-tenofovir group.

INTERPRETATION:

Doravirine (100 mg) and islatravir (0·25 mg) is a two-drug, once daily regimen with efficacy and safety similar to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) for initial treatment of HIV-1, which could provide an option for treatment without an integrase strand transfer inhibitor.

FUNDING:

Merck Sharp & Dohme, a subsidiary of Merck & Co.

01 Feb 2026·LANCET

Switch to fixed-dose doravirine (100 mg) and islatravir (0·25 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, multicentre, randomised, controlled, double-blind, non-inferiority trial

Article

Author: Su, Feng-Hsiu ; Colson, Amy E ; Mills, Anthony M ; Ramgopal, Moti N ; Johnson, Margaret ; Katner, Harold P ; Crofoot, Gordon ; Lahoulou, Rima ; Diamond, Tracy L ; Barninger, Erika ; Fox, Michelle C ; Bettacchi, Christopher ; Osiyemi, Olayemi O ; Eves, Karen ; Klopfer, Stephanie O ; Stamm, Luisa M ; Xu, Yayun ; Gatanaga, Hiroyuki ; Hinestrosa, Federico

BACKGROUND:

The combination of doravirine and islatravir is under investigation as a fixed-dose, single-tablet regimen for the treatment of HIV-1. We aimed to assess the efficacy and safety of switching to doravirine (100 mg) and islatravir (0·25 mg) from bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV-1.

METHODS:

This phase 3, randomised, controlled, double-blind, non-inferiority trial was conducted at 49 research, community, and hospital-based clinics in six countries: Australia, Chile, Israel, Japan, the UK, and the USA. Adults aged 18 years or older with HIV-1, who were virologically suppressed (with a viral load of HIV-1 RNA <50 copies per mL) for at least 3 consecutive months on bictegravir, emtricitabine, and tenofovir alafenamide and had no history of treatment failure or known resistance to doravirine, were eligible for the study. Participants were randomly assigned, in a 2:1 ratio according to a computer-generated randomisation schedule with a block size of three, to switch to oral doravirine (100 mg) and islatravir (0·25 mg) or to continue bictegravir, emtricitabine, and tenofovir alafenamide, once daily. Participants, investigators, study staff, and sponsor personnel were masked to study treatment; sponsor personnel directly involved in this analysis were unmasked at week 48. The primary endpoint, which was assessed in all randomly assigned participants who received at least one dose of study treatment, was the percentage of participants with a viral load of 50 copies per mL or higher at week 48 according to the US Food and Drug Administration snapshot approach; non-inferiority would be concluded if the upper bound of the multiplicity-adjusted 95% CI for the treatment difference was less than 4%. The trial is registered at ClinicalTrials.gov, NCT05630755, and is ongoing but closed to enrolment.

FINDINGS:

Between Feb 17 and Nov 17, 2023, 585 individuals were screened, of whom 514 were randomly assigned and 513 treated: 342 participants were switched to doravirine (100 mg) and islatravir (0·25 mg) and 171 continued bictegravir, emtricitabine, and tenofovir alafenamide. The median age of the 513 participants was 47 years (IQR 37-58), 403 (79%) were assigned male and 110 (21%) were assigned female at birth, 158 (31%) were Black or African American, and 117 (23%) were Hispanic, Latino, or Latina. At week 48, doravirine and islatravir showed non-inferiority to bictegravir, emtricitabine, and tenofovir alafenamide (viral load ≥50 copies per mL in five [1·5%] of 342 vs one [0·6%] of 171 participants) with a treatment difference of 0·9% (multiplicity-adjusted 95% CI -1·9 to 2·9). The rates of adverse events (74·6% [255 of 342 participants] vs 71·3% [122 of 171 participants]; difference 3·2 [95% CI -4·7 to 11·6]), treatment-related adverse events (10·2% [35] vs 9·4% [16]; 0·9 [-5·1 to 6·0]), serious adverse events (4·4% [15] vs 6·4% [11]; -2·0 [-7·1 to 1·9]), and discontinuations due to adverse events (2·9% [ten] vs 1·8% [three]; 1·2 [-2·3 to 3·9]) were similar in the doravirine and islatravir group and the bictegravir, emtricitabine, and tenofovir alafenamide group, and no deaths were reported.

INTERPRETATION:

The combination of doravirine (100 mg) and islatravir (0·25 mg) has similar efficacy and safety profiles to bictegravir, emtricitabine, and tenofovir alafenamide, and could provide a two-drug, once daily, oral single-tablet option without an integrase strand-transfer inhibitor for adults who are virologically suppressed and want to switch to a different ART regimen.

FUNDING:

Merck Sharp & Dohme, a subsidiary of Merck & Co.

01 Feb 2026·LANCET

Switch to fixed-dose doravirine (100 mg) and islatravir (0·25 mg) once daily in virologically suppressed adults with HIV-1 on oral antiretroviral therapy: 48-week results of a phase 3, multicentre, randomised, open-label, non-inferiority trial

Article

Author: Grandhi, Anjana ; Jackson, Beth ; Mngqibisa, Rosie ; Kim, Jason ; Bloch, Mark ; Diamond, Tracy L ; Tebas, Pablo ; Braun, Dominique L ; Fuszard, Monica ; Orkin, Chloe ; Fox, Michelle C ; Kumar, Princy ; Klopfer, Stephanie O ; Walmsley, Sharon ; Eves, Karen ; Carr, Andrew ; Stamm, Luisa M ; Velez, Juan Diego ; Yokomaku, Yoshiyuki

BACKGROUND:

Doravirine and islatravir is an investigational, once-daily, single-tablet regimen containing two potent antiretrovirals with complementary mechanisms of action and resistance profiles. We aimed to evaluate the efficacy and safety of switching from stable, oral antiretroviral therapy (ART) to the fixed combination of doravirine (100 mg) and islatravir (0·25 mg) in virologically suppressed adults living with HIV-1.

METHODS:

This phase 3, randomised, active-controlled, open-label, non-inferiority trial was conducted at 53 research, community, and hospital-based clinics in eight countries: Australia, Canada, Colombia, Japan, South Africa, Switzerland, the UK, and the USA. Adults (aged ≥18 years) with a viral load of fewer than 50 copies of HIV-1 RNA per mL on any oral, two-drug or three-drug ART regimen for at least 3 months, with no history of treatment failure, known resistance to doravirine, or active hepatitis B infection, were randomly assigned (2:1) according to a computer-generated randomisation schedule (block size three) to receive oral doravirine (100 mg) and islatravir (0·25 mg) once daily or to continue baseline ART for 48 weeks. Randomisation was stratified by the anchor antiretroviral drug class (integrase strand-transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor, or protease inhibitor) in the baseline regimen. The primary endpoint (assessed in all treated participants) was the percentage of participants with a viral load of 50 copies per mL or higher at week 48 (analysed according to the US Food and Drug Administration snapshot approach); non-inferiority would be concluded if the upper bound of the multiplicity-adjusted 95% CI for the treatment difference was less than 4%. The safety analysis population included all randomly assigned participants who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, NCT05631093, and is ongoing but closed to enrolment.

FINDINGS:

Between Feb 20 and Oct 24, 2023, 614 individuals were screened for eligibility, of whom 553 were randomly assigned to receive doravirine and islatravir (n=368) or baseline ART (n=185). 551 participants received at least one dose of allocated medication: 366 in the doravirine and islatravir group and 185 in the baseline ART group. Of these 551 participants, 332 (60%) were assigned male and 219 (40%) were assigned female at birth, and the median age was 51 years (IQR 41-59); 250 (45%) identified as Black or African American and 80 (15%) identified as Hispanic, Latino, or Latina. Doravirine and islatravir showed non-inferiority at week 48, with viral loads of 50 copies per mL or higher in five (1·4%) of 366 participants versus nine (4·9%) of 185 participants on baseline ART (difference -3·6% [multiplicity-adjusted 95% CI -7·8 to -0·8]). Treatment-related adverse events were more common with doravirine and islatravir (44 [12·0%] of 366 participants) than with baseline ART (nine [4·9%] of 185 participants; difference 7·2 [95% CI 2·2 to 11·6]). Rates were similar in the doravirine and islatravir group and the baseline ART group for any adverse event (79·5% [291 of 366 participants] vs 83·8% [155 of 185 participants]; difference -4·3 [-10·7 to 2·8]), serious adverse events (6·3% [23] vs 4·9% [nine]; 1·4 [-3·2 to 5·2]), and discontinuation due to adverse events (0·5% [two] vs 2·2% [four]; -1·6 [-4·9 to 0·2]). One death occurred (in the baseline ART group) and was not considered treatment-related. No participants discontinued treatment as a result of protocol-specified declines in CD4 cell or total lymphocyte counts.

INTERPRETATION:

Doravirine and islatravir is efficacious and well tolerated and would represent the first non-INSTI-based, two-drug regimen for HIV-1 treatment. With increasing concern over the potential development of widespread INSTI resistance, this once-daily, oral, single-tablet regimen could be a potential option for people living with HIV-1 requiring a change to their antiretroviral regimen. The safety and efficacy findings support the ongoing development of islatravir, a drug with long-acting potential.

FUNDING:

Merck Sharp & Dohme, a subsidiary of Merck & Co.

News (Medical) associated with Doravirine/Islatravir

22 Jul 2026

·www.biospace.com

Investigational Once-Weekly Oral HIV Treatment Regimen of Islatravir and Lenacapavir Maintained Virological Suppression in Adults With HIV Who Switched Antiretroviral Therapy

– High Rates of Virologic Suppression Sustained at Week 48 Across ISL/LEN Treatment Groups in Both Phase 3 ISLEND Trials – – ISL/LEN has the Potential to be the First Once-Weekly Oral HIV Treatment – FOSTER CITY, Calif. & RAHWAY, N.J.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the detailed outcomes from the Phase 3 ISLEND-1 and ISLEND-2 trials will be presented for the first time at the 26 th International AIDS Conference ( AIDS 2026 ). The primary endpoint results at Week 48 showed that the investigational once-weekly oral single-tablet HIV treatment regimen of islatravir 2 mg/lenacapavir 300 mg (ISL/LEN) was effective in adults living with HIV who were virologically suppressed and switched from global guideline-recommended BIKTARVY ® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) (ISLEND-1) or other standard of care oral daily antiretroviral regimens (ISLEND-2). The safety pro ISL/LEN was generally similar to the comparator regimens studied in the ISLEND trials, and no new safety concerns were identified. Results of both trials will be presented during late-breaking sessions at AIDS 2026 on Wednesday, July 29 and featured in the AIDS 2026 press program on Tuesday, July 21. These data will form the basis of regulatory submissions. The ISLEND-1 ( NCT06630286 ) and ISLEND-2 ( NCT06630299 ) trials evaluated the safety and efficacy of the once-weekly single tablet regimen of ISL/LEN. The data provide strong evidence for the potential of ISL/LEN to be the first and only once-weekly oral HIV treatment option for adults with virologic suppression on a stable antiretroviral regimen. The investigational combination pairs Merck’s islatravir, a next-generation nucleoside analog with multiple mechanisms of action including HIV-1 reverse transcriptase translocation inhibition, with Gilead’s lenacapavir, a first-in-class capsid inhibitor that disrupts HIV-1 at multiple stages of its lifecycle. The potency and pharmacokinetic profiles of islatravir and lenacapavir enable dosing as a complete once-weekly tablet for HIV treatment. ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); Results from ISLEND-1 Week 48 results showed that the once-weekly single tablet regimen of ISL/LEN was noninferior to BIKTARVY in maintaining virologic suppression; no (0%) participants who switched to ISL/LEN had HIV-1 RNA ≥ 50 copies/mL at Week 48 compared to 1 (0.3%) participant who remained on BIKTARVY (as determined by the US FDA-defined snapshot algorithm). “Once-daily, combination, single-tablet antiretroviral therapy is the cornerstone of HIV treatment today. However, the treatment landscape is evolving,” said Jürgen Rockstroh, Department of Medicine University Hospital Bonn, Germany. “Long-acting therapies provide an alternative to daily pills. The ISLEND-1 study results show the potential of ISL/LEN as the first once-weekly oral single-tablet treatment option.” In this blinded trial, treatment-related adverse events were reported in 13.5% of participants who switched to ISL/LEN and 13.2% of participants who remained on BIKTARVY and were generally comparable between groups. In both treatment groups, the most common treatment-related adverse events reported were nausea (3%) and headache (3%). A similar incidence of serious adverse events was reported in both treatment groups (5.3% ISL/LEN; 4.6% BIKTARVY). Discontinuations of ISL/LEN or BIKTARVY due to adverse events were low (2% and 1.7%, respectively). CD4+ T-cell and lymphocyte counts were stable in both treatment groups through Week 48 and no participant discontinued due to a decrease in CD4+ T-cell or lymphocyte count. There was no clinically meaningful difference in changes in body weight between the treatment groups at Week 48. Results from ISLEND-2 At Week 48, ISL/LEN was found to be non-inferior to daily oral standard of care HIV treatments; 0.3% of participants receiving ISL/LEN had HIV-1 RNA ≥ 50 copies/mL compared to 1.3% who remained on standard of care antiretroviral regimens (as determined by the US FDA-defined snapshot algorithm). “Single tablet regimens have transformed the outlook for millions of people living with HIV,” said Amy Colson, Research Director at Community Resource Initiative and Medical Director of the Zinberg Clinic at Cambridge Health Alliance. “Having a treatment option with once weekly dosing can expand choice to help address individual needs and preferences. The 48-week findings provide the evidence for ISL/LEN as the potential first once-weekly oral treatment option to help support long-term treatment needs and be responsive to the preferences of people living with HIV.” In this open-label trial, treatment-related adverse events were reported in 18% of participants treated with ISL/LEN and <1% receiving standard of care antiretroviral regimens. In the ISL/LEN group, the most common treatment-related adverse events reported (≥2%) were headache (5%), nausea (3%) and diarrhea (3%). Discontinuations of study drug due to adverse events were low (1% and <1%, respectively). CD4+ T-cell counts and lymphocyte counts were stable in both treatment groups through Week 48 and no participant discontinued due to a decrease in CD4+ T-cell or lymphocyte counts. Through Week 48, body weight remained stable in both treatment groups. Additionally, participants who switched to once-weekly oral ISL/LEN reported higher treatment satisfaction and lower treatment burden compared with taking standard of care daily HIV treatments based on HIV Patient Perspective of Regimen Change outcomes reporting. Islatravir and lenacapavir in combination are investigational and not approved for use. There is currently no cure for HIV or AIDS. About ISLEND-1 ISLEND-1 ( NCT06630286 ) is a Gilead-sponsored, multicenter Phase 3 randomized, double-blind, active-controlled trial designed to evaluate the safety and efficacy of switching to a once-weekly tablet of ISL/LEN versus continuing treatment with BIKTARVY (bictegravir/emtricitabine/tenofovir alafenamide) in people with virologically-suppressed HIV (HIV-1 RNA levels < 50 copies/mL) on BIKTARVY for ≥ 6 months prior to screening. Participants were randomized 1:1 to receive initial doses of ISL/LEN on Day 1 and Day 2 followed by once-weekly ISL/LEN from Day 8 to Week 96 plus placebo-to-match BIKTARVY daily, or BIKTARVY daily plus placebo-to-match initial doses of ISL/LEN on Day 1 and Day 2 and placebo-to-match once-weekly ISL/LEN from Day 8 to Week 96. The study will remain blinded until all participants complete their Week 96 visit. The primary endpoint was the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48, as determined by the US FDA-defined snapshot algorithm. Key secondary endpoints included the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96, as determined by the US FDA-defined snapshot algorithm; the proportion of participants with virologic suppression (HIV viral load < 50 copies/mL per US FDA Snapshot) at Week 48 and Week 96; change from baseline in CD4 cell count at Week 48 and Week 96; and the proportion of participants treated with ISL/LEN who discontinued treatment due to treatment-emergent adverse events. About ISLEND-2 ISLEND-2 ( NCT06630299 ) is a Gilead-sponsored, multicenter Phase 3 randomized, open-label, active-controlled trial evaluating the safety and efficacy of switching to a once-weekly tablet of ISL/LEN versus continuation of standard of care treatment in people with virologically-suppressed HIV (HIV-1 RNA levels < 50 copies/mL) on a stable standard of care antiretroviral regimen for ≥ 6 months prior to screening. A standard of care regimen included two or three antiretroviral medicines, including integrase strand transfer inhibitors (INSTI), nucleoside reverse transcriptase inhibitors (NRTIs), boosted protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI). Participants were randomized 1:1 to receive initial doses of ISL/LEN on Day 1 and Day 2 followed by once-weekly ISL/LEN from Day 8 to Week 96 or to continue their daily oral standard of care treatment with two or three antiretroviral medicines up to Week 96. The primary endpoint is the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 by FDA-defined Snapshot Algorithm. Key secondary endpoints included the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 96, as determined by the US FDA-defined snapshot algorithm; the proportion of participants with virologic suppression (HIV viral load < 50 copies/mL per US FDA Snapshot) at Week 48 and Week 96; change from baseline in CD4 cell count at Week 48 and Week 96; and the proportion of participants treated with ISL/LEN who discontinued treatment due to treatment-emergent adverse events. Patient-reported outcomes are an exploratory outcome of this open-label trial. About Lenacapavir The multi-stage mechanism of action of lenacapavir is distinguishable from other approved classes of antiretroviral agents. While most antiretrovirals act on one stage of viral replication, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle and has no known exhibited cross-resistance in vitro to other existing drug classes. Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV treatment and prevention research program. Lenacapavir is being developed as a foundation for potential future HIV therapies to offer both long-acting oral and injectable options with several dosing frequencies, in combination or as a mono-agent, that help address the individual needs and preferences of people and communities affected by HIV. For an overview of Gilead’s HIV treatment and prevention clinical development program, please click here . About Islatravir (MK-8591) Islatravir (MK-8591) is Merck’s potent, next-generation nucleoside analog that blocks HIV-1 replication by multiple mechanisms including inhibition of reverse transcriptase translocation, resulting in immediate chain termination, and induction of structural changes in the viral DNA (delayed chain termination). Islatravir is anchoring multiple ongoing early and late-stage clinical trials of two-drug regimens in combination with other Merck antiretrovirals for potential treatments for HIV-1. Islatravir is being studied in Phase 3 in combination with Merck’s doravirine (DOR/ISL) as a once-daily pill for treatment of HIV-1 infection in adults with no prior antiviral treatment history and in Phase 2b in combination with Merck’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) as an oral once-weekly treatment for HIV-1. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here . About Gilead HIV For almost 40 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 13 HIV medications , including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to help reduce new HIV infections, and the first long-acting injectable HIV prevention medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a treatable, preventable, chronic condition for millions of people. Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships , collaborations and charitable giving, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic worldwide. Gilead has been repeatedly recognized as the top two leading philanthropic funders of HIV-related programs in a report released by Funders Concerned About AIDS. Discover more about Gilead’s unique collaborations worldwide and the work to help end the HIV epidemic. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer and inflammation. In 2025, Gilead announced a planned $32 billion investment to further strengthen its U.S. footprint to power the next era of discovery, job creation and public health preparedness – while continuing to invest globally to ensure patients everywhere benefit from its scientific innovation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. Merck’s Commitment to HIV For more than 40 years, Merck has been committed to research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has helped pioneer the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options for both HIV treatment and prevention. We’re inspired by the lived experiences of the HIV community as we advance research with real life in mind. Our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives to help end the HIV epidemic. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . Gilead Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials or studies, including those involving lenacapavir (such as ISLEND-1 and ISLEND-2); uncertainties relating to regulatory applications and related filing and approval timelines, including potential applications for programs and/or indications currently under evaluation, such as oral once-weekly single-tablet HIV treatment regimen of islatravir/lenacapavir, and the risk that any regulatory approvals, if granted, may be subject to significant limitations on use or subject to withdrawal or other adverse actions by the applicable regulatory authority; the possibility that Gilead may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2025 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( ). BIKTARVY, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies. All other marks are the property of their respective owners. For more information about Gilead, please visit the company’s website at , follow Gilead on X ( @Gilead Sciences ) and LinkedIn , or contact Gilead Public Affairs. Contacts GILEAD CONTACTS: Priscilla White, Media public_affairs@gilead.com Jacquie Ross, Investors investor_relations@gilead.com MERCK CONTACTS: Melissa Moody, Media mediarelations@merck.com Peter Dannenbaum, Investors investor_relations@merck.com

Phase 3Clinical ResultPhase 2

21 Jul 2026

·www.fiercepharma.com

Gilead, Merck’s phase 3 data back first weekly HIV pill

Detailed phase 3 results suggest the two-drug combination of Gilead Sciences’ lenacapavir and Merck & Co.’s islatravir has what it takes to become the first complete weekly pill for the treatment of HIV. Two Islend clinical trials confirmed that a once-weekly, single-tablet combination of islatravir and lenacapavir (ISL/LEN) matches daily treatments like Gilead’s Biktarvy at maintaining HIV viral suppression, according to data slated for presentation at the 26th International AIDS Conference in Rio de Janeiro, Brazil. Positioned to become the first complete weekly oral HIV treatment, ISL/LEN combines a major scientific leap with the promise of meeting diverse patient needs, Jared Baeten, M.D., Ph.D., Gilead’s clinical development lead in virology, said in an interview with Fierce Pharma. “Many people living with HIV struggle with adherence,” Baeten said. “Once-a-week pills take […] the psychological challenges of HIV adherence from seven days a week to one.” The weekly ISL/LEN pill was efficacious and well tolerated at least up to Week 48 in the two Islend trials. In the Islend-1 study among 607 participants who already had their HIV well under control with Biktarvy, no individuals who switched to ISL/LEN had detectable HIV of at least 50 copies/mL at Week 48, compared with one (0.3%) case in those who remained on Biktarvy. Patients who got ISL/LEN saw their CD4+ T-cell count changed by an average minus 10 cells/μL, compared with minus 18 cells/μL in the control arm. The patients started the trial with CD4 counts at around 740 cells/μL, well above the 500 cells/μL threshold considered normal. As for Islend-2, that study enrolled 626 individuals who were virologically suppressed by various daily regimens. At Week 48, one (0.3%) ISL/LEN recipient and four (1.3%) patients who continued their standard treatments had HIV RNA levels reach 50 copies/mL or above. Average change in CD4 counts was minus 45 cells/μL with ISL/LEN and minus 8 cells/μL with daily orals. As the researchers noted in an abstract, the ISL/LEN group had higher baseline CD4 counts, while the two groups’ numbers converged at Week 48. The FDA once temporarily placed several Merck studies of islatravir on clinical hold in 2021 after some patients had experienced notable declines in total lymphocyte and CD4 T-cell counts. As Baeten pointed out, the safety signal was triggered by high dose levels of islatravir that was significantly higher than used in the Islend trials. In both Islend trials, investigators reported “no between-group differences” in lymphocyte counts at Week 48, according to their abstracts. In both trials, ISL/LEN demonstrated a safety profile that’s comparable to daily orals. All study arms had treatment-emergent adverse events of any grade in the high-70s percentage range. The rate of any-grade adverse events deemed treatment-related was 13.5% and 13.2% for ISL/LEN and Biktarvy, respectively, in Islend-1; and 18.5% and 0.3% for the weekly pill and control arm, respectively, in Islend-2. Treatment-related serious adverse reactions or treatment-related problems leading to discontinuation were generally low across both trials, in the low single digits or below. Before ISL/LEN’s clinical success, GSK already introduced the world’s first complete long-acting HIV treatment, Cabenuva, which replaces daily pills with injections given once a month or every two months. Still, many patients prefer taking pills over injecting themselves, Baeten noted. On the flip side, many patients who’re comfortable taking pills every day may stick with their daily routine. What ISL/LEN offers is another option, he said. “We are laser-focused on getting enough options to patients so that every one of them can find the thing that’s going to work for them for the long term because HIV treatment is a decades-long exercise,” Baeten said. While ISL/LEN could offer a once-weekly treatment option, the California pharma is developing new antivirals in the hopes of matching lenacapavir’s six-month dosing capability. In one approach, Gilead is launching two phase 3 studies in the Daybreak program combining lenacapavir with two broadly neutralizing antibodies, teropavimab and zinlirvimab. The positive HIV treatment readout comes as Gilead is making commercial inroads for lenacapavir, an HIV capsid inhibitor, as a twice-yearly PrEP injection for HIV prevention. Approved by the FDA a year ago under the brand name Yeztugo , the long-acting injectable booked $166 million in sales in the first quarter. At AIDS 2026, Gilead provided updated results from the landmark Purpose trials for Yeztugo through a year of open-label extension that Baeten said reinforce the drug’s profile. Of 4,417 cisgender women enrolled in the Purpose 1 trial who were eligible to join the open-label stage following the original randomized blinded phase, 95% chose to start or continue Yeztugo. There were zero HIV infections among all those individuals during the 52 weeks of follow-up. By comparison, one infection was reported in a woman who switched from blinded Yeztugo to Gilead’s daily PrEP Truvada during the open-label phase. In Purpose 2, which enrolled cisgender men and gender-diverse individuals, a similar 95% of participants opted to take Yeztugo during the open-label phase. One case of HIV occurred in a person who received all Yeztugo injections on time. Despite that additional case, Yeztugo still boasts the lowest chance of breakthrough infection as seen in a PrEP clinical trial, Baeten said. All told, in Purpose-2, there were four HIV infections for Yeztugo over 5,295 person-years of follow-up so far. Typically, in this population, the expected HIV incidence rate is around 3% to 5% per year, the Gilead exec noted. The fact that 95% of participants chose to take Yeztugo is in itself “a striking number,” Baeten noted. Besides, adherence to timely injections was high, at 96% and 92%, respectively, at week 52 between the two trials. “Adherence is the Achilles’ heel of PrEP, and lenacapavir, by being an injection of just twice a year, takes much of that adherence out of people’s hands,” Baeten said. Both Gilead and researchers are evaluating in various studies how best to keep adherence to Yeztugo high, Baeten noted. For its part, Merck recently got FDA approval for islatravir, a nucleoside reverse transcriptase translocation inhibitor (NRTTI), as part of a daily combination with doravirine under the brand name Idvynso . After failing to turn islatravir into a PrEP option because of the dosing strength problem, Merck is developing a follow-on NRTTI, alimatravir (MK-8527), as a potential once-monthly oral pill for PrEP. Trying to build its own once-weekly oral treatment without Gilead’s lenacapavir, the New Jersey pharma is investigating pairing islatravir with an NNRTI called ulonivirine in phase 2.

Clinical ResultPhase 3Phase 2Drug Approval

15 Jul 2026

·www.biospace.com

Merck to Present New Data on Daily, Weekly, and Monthly Options Across its HIV Treatment and Prevention Pipeline at AIDS 2026

Late-breaker presentations will highlight investigational, once-weekly oral combinations of islatravir with lenacapavir (Phase 3 ISL/LEN) and with ulonivirine (Phase 2b ISL+ULO) in adults with virologically-suppressed HIV-1 RAHWAY, N.J.--(BUSINESS WIRE)-- $MRK #MRK --Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that new data from its research pipeline for HIV treatment and prevention will be presented at the 26th International AIDS Conference (AIDS 2026), taking place July 26-31, 2026, in Rio de Janeiro, Brazil. “Building on the momentum of the recent FDA approval of IDVYNSO, AIDS 2026 is an exciting moment to showcase the next chapter of Merck’s HIV pipeline – particularly our focus on the potential of once-weekly oral treatments in combination with islatravir,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “The breadth of new data spanning our daily, weekly and monthly investigational regimens developed for HIV treatment and prevention demonstrates how Merck’s research is continuing to evolve with the needs of the HIV community.” Oral late-breaker presentations at AIDS 2026 by program: ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); Islatravir/Lenacapavir Primary results of Week 48 efficacy and safety data from the pivotal, Phase 3 ISLEND-1 trial evaluating switch to investigational once-weekly oral islatravir and lenacapavir (ISL/LEN) compared to continuing daily regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in adults with virologically-suppressed HIV-1 (Abstract #OAB1406LB). Primary results of Week 48 efficacy and safety data from pivotal Phase 3 ISLEND-2 trial evaluating switch to investigational once-weekly oral islatravir and lenacapavir (ISL/LEN) compared to continuing daily standard of care in adults with virologically-suppressed HIV-1 (Abstract #OAX1106LB). Islatravir + Ulonivirine Primary results of Week 24 efficacy and safety data from the Phase 2b MK-8591B-060 trial evaluating switch to investigational once-weekly oral islatravir and ulonivirine (ISL + ULO) compared to continuing daily BIC/FTC/TAF in adults with virologically-suppressed HIV-1 (Abstract #OAB1405LB). Doravirine/Islatravir Switching to doravirine/islatravir (100/0.25 mg) once-daily maintained viral suppression at Week 96 in the presence of baseline NNRTI resistance-associated mutations and/or M184I/V in proviral DNA (Abstract #OAB0105LB). Merck symposia during AIDS 2026 Merck will host a policy symposium entitled “ Access where it counts: Expanding PrEP beyond clinics ” on Wednesday, July 29, from 18:00 – 19:30 (BRT/UTC-3). Merck will also host a medical symposium entitled “Evolving standards in HIV care: Resistance, cardiometabolic health, and care for older adults ” on Wednesday, July 29, from 12:00 – 13:00 (BRT/UTC-3). Both events will be open to registered attendees, virtually and in-person. Merck Investor Event Merck will hold a virtual HIV Investor Event on Monday, August 3, 2026, at 8:00 a.m. ET, during which senior management will provide an update on the company’s HIV program and strategy. Investors, analysts, members of the media, and the general public are invited to listen to a webcast of the presentation via this weblink . All participants may join the call by dialing (888) 790-1829 (U.S. and Canada Toll-Free) or (210) 839-8800 and using the access code 6773537. Details on abstracts listed above and select additional abstracts: Abstract Title and Presenting Author Date HIV Treatment Once-weekly oral islatravir/lenacapavir (ISL/LEN) versus daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in virologically-suppressed adults with HIV-1: Week 48 results of the ISLEND-1 phase 3 trial. J. Rockstroh.* Abstract #OAB1406LB Oral Presentation ARTistic Strategies 2: The Long Game Wednesday, July 29, 2026 15:00-16:00 PM BRT Once-weekly oral islatravir/lenacapavir (ISL/LEN) versus daily standard-of-care therapy in virologically-suppressed adults with HIV-1: week 48 results of the ISLEND-2 phase 3 trial. A. Colson.* Abstract #OAX1106LB Oral Presentation AIDS 2026: Co-Chair’s Choice Wednesday, July 29, 2026 10:30-11:30 AM BRT Randomized, active-controlled, phase 2b study evaluating efficacy and safety of switch to islatravir (ISL) 2 mg with ulonivirine (ULO) 200 mg once-weekly in virologically suppressed adults living with HIV-1. A. Luetkemeyer. Abstract #OAB1405LB Oral Presentation ARTistic Strategies 2: The Long Game Wednesday, July 29, 2026 15:00-16:00 PM BRT Switching to doravirine/islatravir (100/0.25mg) once-daily maintained viral suppression at week 96 in the presence of baseline NNRTI resistance-associated mutations and/or M184I/V in proviral DNA. T. Diamond. Abstract #OAB0105LB Oral Presentation ARTistic Strategies 1: From Testing to Treatment Tuesday, July 28, 2026 10:30-11:30 AM BRT Simplification to single-tablet doravirine/islatravir from complex antiretroviral regimens: subgroup analysis from a randomized, open-label, phase 3 clinical study. M. Fox. Abstract #LB23 Poster exhibition Tuesday, July 28, 2026 Wednesday, July 29, 2026 Thursday, July 30, 2026 12:00-1:00 PM BRT Efficacy and safety by subgroup of doravirine/islatravir (100 mg/0.25 mg) once daily as initial HIV-1 therapy: week 48 results from a randomized, active-controlled Phase 3 study. B. Crabtree-Ramírez. Abstract #WEPEB089 Poster exhibition Wednesday, July 29, 2026 12:00-1:00 PM BRT Open-label Phase 1 study to evaluate relative bioavailability and food effect on the pharmacokinetics of the fixed-dose combination of doravirine/islatravir (100 mg/0.25 mg) in adults without HIV. S. Stanley. Abstract #EP054 E-poster Monday, July 27, 2026 14:00 PM BRT Comorbidity and comedication burden in people living with HIV stratified by age and sex. S. Fleming. Abstract #TUPEB079 Poster exhibition Tuesday, July 28, 2026 12:00-1:00 PM BRT Opti-DOR: 48-week data on DOR/3TC/TDF as an alternative first-line antiretroviral therapy (ART) regimen to integrase inhibitors for people with HIV and BMI>25 kg/m 2 in a randomized Phase 3b non-inferiority study. J. Woods.** Abstract #OAB3406LB Oral Presentation Metabolic complications: The eye of the storm Friday, July 31, 2026 10:30-11:30 AM BRT HIV Prevention MK-8527 de novo resistance selection in HIV-1 subtypes A, B, and C and prevalence of M184I/V mutations in persons diagnosed with HIV without a known history of HIV treatment. T. Diamond. Abstract #LB27 Poster exhibition Tuesday, July 28, 2026 Wednesday, July 29, 2026 Thursday, July 30, 2026 12:00-13:00 PM BRT Open-label Phase 1 study to characterize the effects of a strong CYP3A4 inducer on the pharmacokinetics of MK-8527, a nucleoside reverse transcriptase translocation inhibitor, in adults without HIV. R. Carstens. Abstract #TUPEB125 Poster exhibition Tuesday, July 28, 2026 12:00-1:00 PM BRT Open-label Phase 1 study of the effects of emtricitabine and tenofovir disoproxil fumarate on the pharmacokinetics of MK-8527, a nucleoside reverse transcriptase translocation inhibitor, in adults without HIV. R. Carstens. Abstract #WEPEC183 Poster exhibition Wednesday, July 29, 2026 12:00-1:00 PM BRT Features of HIV-1 acquisition in adults receiving pre-exposure prophylaxis as part of the IMPOWER-22 and IMPOWER-24 open-label phase. R. Landovitz. Abstract #WEPEC175 Poster exhibition Wednesday, July 29, 2026 12:00-1:00 PM BRT PrEP modality preferences by psychosocial phenotypes of gay, bisexual, and other men who have sex with men using latent class analysis. R. Gravett. Abstract #TUPEC172 Poster exhibition Tuesday, July 28, 2026 12:00-1:00 PM BRT *In collaboration with Gilead **Merck-supported, investigator-initiated study About islatravir (MK-8591) and Merck’s HIV research Islatravir (MK-8591) is Merck’s potent, next-generation nucleoside analog reverse transcriptase inhibitor that blocks HIV-1 replication by multiple mechanisms, including inhibition of reverse transcriptase translocation, resulting in immediate chain termination, and induction of structural changes in the viral DNA (delayed chain termination). Islatravir is under evaluation in multiple ongoing early and late-stage clinical trials in combination with other antiretrovirals for potential treatments for HIV-1. Islatravir is available in combination with Merck’s s non-nucleoside reverse transcriptase inhibitor (NNRTI), doravirine, in the United States and Japan as IDVYNSO™, a new, once-daily, single-tablet regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine. Islatravir continues to be studied in Phase 3 in combination with Merck’s doravirine (DOR/ISL) as a once-daily pill for treatment of HIV-1 infection in adults with no prior antiviral treatment history; in combination with Gilead’s lenacapavir in Phase 3 development as a novel once-weekly oral treatment for HIV-1 (ISLEND-1 [ NCT06630286 ] and ISLEND-2 [ NCT06630299 ]); and in combination with Merck’s investigational NNRTI ulonivirine (MK-8507) in Phase 2b development (MK-8591B-060 [ NCT06891066 ] and MK-8591B-062 [ NCT07266831 ]) as an once-weekly oral treatment. MK-8527 (alimatravir) is the company’s investigational, novel, once-monthly oral candidate for pre-exposure prophylaxis (PrEP) for HIV-1. In collaboration with the Gates Foundation, the Phase 3 EXPrESSIVE-10 trial (MK-8527-010, NCT07071623 ) is evaluating the safety and efficacy of MK-8527 as PrEP to reduce the risk of sexually acquired HIV-1 infection among women and adolescent girls in sub-Saharan Africa. The Phase 3 EXPrESSIVE-11 trial (MK-8527-011, NCT07044297 ) is evaluating the safety and efficacy of MK-8527 as PrEP to reduce the risk of sexually acquired HIV-1 infection among people likely to be exposed to HIV-1 in 16 countries. Both trials are now enrolling. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here . Merck’s Commitment to HIV For more than 40 years, Merck has been committed to research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has helped pioneer the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options for both HIV treatment and prevention. We’re inspired by the lived experiences of the HIV community as we advance research with real life in mind. Our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives to help end the HIV epidemic. Selected Safety Information for IDVYNSO Contraindications IDVYNSO is contraindicated when co-administered with: drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of IDVYNSO. lamivudine (3TC) or emtricitabine (FTC) as significant decreases in islatravir-triphosphate (ISL-TP) concentrations may occur, which may decrease the effectiveness of IDVYNSO. (See Drug Interactions) Warnings and Precautions Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during postmarketing experience with doravirine-containing regimens. In addition, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) was reported with IDVYNSO in a clinical trial. Discontinue IDVYNSO, and other medications associated with these reactions, immediately if a painful rash with mucosal involvement, a progressive severe rash, or a rash with constitutional symptoms, eosinophilia, lymphadenopathy, or other organ involvement develops. Close clinical monitoring, and appropriate therapy should be initiated. The concomitant use of IDVYNSO and certain other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effect of IDVYNSO and possible development of resistance and possible clinically significant adverse reactions from greater exposures of a component of IDVYNSO. Consider the potential for drug interactions prior to and during IDVYNSO therapy, review concomitant medications during IDVYNSO therapy, and monitor for adverse reactions. (See Drug Interactions) Adverse Reactions The most common adverse reactions (incidence ≥ 2%, all grades in any treatment group) reported in virologically suppressed participants in the IDVYNSO treatment groups from 2 clinical trials, respectively, were: diarrhea (3% and 1%), dizziness (2% and 1%), fatigue (2% and 1%), abdominal distension (2% and 1%), headache (2% and 1%) and increased weight (2% and <1%). A single case of severe immune thrombocytopenia (platelet count nadir of 2 x10⁹/L) characterized by abrupt onset of subcutaneous hematoma, petechiae, and hematuria was reported in a participant 32 days after initiating IDVYNSO. The case resolved with discontinuation of IDVYNSO, in conjunction with treatments including corticosteroids and IVIG. Among all participants in Trials 052 and 051, there were no patterns of platelet decreases over time with IDVYNSO and no differences between treatment arms in mean change from baseline in platelet count. Drug Interactions IDVYNSO is a complete regimen; co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. Co-administration of IDVYNSO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce the efficacy of IDVYNSO. If IDVYNSO is co-administered with rifabutin, one tablet of doravirine should be taken approximately 12 hours after the dose of IDVYNSO. Co-administration of IDVYNSO with other moderate CYP3A inducers is not recommended. Co-administration of IDVYNSO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. Co-administration of IDVYNSO is not recommended with deoxycytidine kinase (dCK) substrates (e.g., nucleoside antimetabolites) as they may reduce the exposure of islatravir-triphosphate or with adenosine deaminase (ADA) inhibitors (e.g., pentostatin) as they may increase the exposure of islatravir. (see Contraindications) Use in Specific Populations There are insufficient human data on the use of IDVYNSO during pregnancy to inform a drug-associated risk of birth defects and miscarriage. Healthcare providers are encouraged to call the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263 to report pregnancy outcomes in individuals exposed to IDVYNSO. It is unknown whether IDVYNSO or any of its components are present in human milk, affects human milk production, or has effects on the breastfed infant. Inform patients that the potential risks of breastfeeding include: (1) HIV-1 transmission (in infants without HIV-1), (2) developing viral resistance (in infants with HIV-1), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults. Clinical trials in virologically suppressed participants who received IDVYNSO included 81 (11%) participants aged 65 years and older, including 10 (1%) aged 75 years and older. Overall differences in response have not been identified between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No dosage adjustment of IDVYNSO is required in patients with eGFR ≥30 mL/min/1.73 m2. IDVYNSO is not recommended in patients with eGFR <30 mL/min/1.73 m2 and has not been studied in participants undergoing dialysis. No dosage adjustment of IDVYNSO is recommended in patients with mild or moderate hepatic impairment (Child- Pugh Class A or B). IDVYNSO has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and therefore is not recommended in these patients. IDVYNSO does not have activity against hepatitis B virus (HBV). Patients with HBV coinfection who switch to IDVYNSO from an antiretroviral regimen with activity against HBV, and patients on IDVYNSO who are newly diagnosed with HBV coinfection, should be closely monitored and specific anti-HBV therapy should be considered, as clinically appropriate. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2025 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( ). Please see Prescribing Information for IDVYNSO™ (doravirine and islatravir) at and Patient Information for IDVYNSO at . Contacts Media Contacts: Melissa Moody (215) 407-3536 Deb Wambold (215) 779-2234 Investor Contacts: Peter Dannenbaum (732) 594-1579 Ayn Wisler (917) 691-6218

Phase 3Phase 2Clinical ResultPhase 1

100 Deals associated with Doravirine/Islatravir

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
HIV Infections	Japan	MSD KK (Tokyo)	06 Mar 2026

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05630755 \| NCT05631093 \| NCT05766501 (Pubmed \| J Infect Dis)	Phase 3	HIV Infections	1,227	Doravirine/Islatravir (100/0.25 mg)	mljnpsract(axllhqbdeq) = pikqhqwzbo wknmdpdlkp (pyobwghocq )	Positive	29 May 2026
NCT05705349 (MK-8591A-053, Pubmed \| Lancet HIV) Manual	Phase 3	HIV Infections First line	536	doravirine-islatravir	ouvtoxxgvt(typojludvk) = lomwfeubgh wxrtelvetw (dczmpaxqke ) View more	Non-inferior	25 Feb 2026
				bictegravir-emtricitabine-tenofovir	ouvtoxxgvt(typojludvk) = ayhkunppsf wxrtelvetw (dczmpaxqke ) View more
NCT05631093 (MK-8591A-051, Pubmed \| Lancet \| BusinessWire) Manual	Phase 3	HIV Infections	551	doravirine-islatravir	vwwmqxmprp(rnxkdhjbur) = eqvsdcpyux ghuhtzxooi (xryopkjdhf ) Met View more	Non-inferior	07 Feb 2026
				ART	vwwmqxmprp(rnxkdhjbur) = hsrbiclssn ghuhtzxooi (xryopkjdhf ) Met View more
NCT05630755 (MK-8591A-052, Pubmed \| Lancet \| BusinessWire) Manual	Phase 3	HIV Infections	513	doravirine-islatravir	newsuvpmyw(fnzkevxtra) = onydaehgpw jgzovbtmys (nvghdgsljb ) Met View more	Non-inferior	01 Feb 2026
				Bictegravir/Emtricitabine/Tenofovir Alafenamide	newsuvpmyw(fnzkevxtra) = zoxmjopqeh jgzovbtmys (nvghdgsljb ) Met View more
NCT05631093 (MK-8591A-051, CTgov)	Phase 3	HIV Infections	553	DOR+Islatravir (Doravirine/Islatravir (DOR/ISL))	pufmtdprna = gooncnnrge qtdondpmwi (xxvmlvogxm, eggstcnavn - ktileyoost) View more	-	21 Nov 2025
				DOR (Baseline ART + DOR/ISL)	pufmtdprna = kquiezfsfa qtdondpmwi (xxvmlvogxm, pskitkjtwr - gapuijuwla) View more
NCT05630755 (MK-8591A-052, CTgov)	Phase 3	HIV Infections	514	Placebo to BIC/FTC/TAF+DOR/ISL (DOR/ISL and Placebo to BIC/FTC/TAF)	jkszazejye = wptxzudzjk kibydtywkl (watkjamepy, lnacjorytt - zwyhiivrlg) View more	-	18 Nov 2025
				Placebo to DOR/ISL+BIC/FTC/TAF (BIC/FTC/TAF and Placebo to DOR/ISL)	jkszazejye = itwiwfsouc kibydtywkl (watkjamepy, ioplozagxa - pmvvqqnsjp) View more
NCT05630755 (MK-8591A-052, Company_Website)	Phase 3	HIV Infections	513	placebo+Doravirine+Islatravir-MK8591A	gtaietjpqo(ojfdiabhzx) = uxcvjqbqtt gtfhwuscig (niefaznrai ) View more	Positive	15 Oct 2025
				placebo+Bictegravir+Tenofovir alafenamide+Emtricitabine	gtaietjpqo(ojfdiabhzx) = eigabdkfji gtfhwuscig (niefaznrai ) View more
NCT04233879 (Pubmed \| Clin Infect Dis)	Phase 3	HIV Infections	597	Doravirine/islatravir (100/0.75 mg)	xamjdmbein(fdunqtrrtp) = AEs leading to discontinuations were higher with doravirine/islatravir (8.7%, 3.7%) due to protocol-specified criteria requiring discontinuation for decreased CD4 and lymphocyte counts bkengxjxzy (twnakyrpjd ) View more	-	16 Sep 2025
				Bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg)
NCT04223778 (8591A-017 \| MK-8591A-017, CTgov)	Phase 3	HIV Infections	672	DOR/ISL (Group 1: Doravirine/Islatravir (DOR/ISL))	gsfxromfic = ncxspmzeeo keopvajgcx (eywsobyxaa, shnwnonijc - ezunqrtkjd) View more	-	19 Sep 2022
				ART+DOR/ISL (Group 2: Baseline Antiretroviral Therapy (ART))	gsfxromfic = nhhhrgvrnz keopvajgcx (eywsobyxaa, wjjnejqanm - durvkkswnp) View more

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