doravirine/islatravir (MK-8591A) / Merck (MSD) - LARVOL DELTA

Switching to Doravirine/Islatravir (100 mg/0.25 mg) Once Daily Maintained Viral Suppression in the Presence of Archived M184I/V Resistance-Associated Mutations in Proviral DNA (IAS-HIV 2025) - "The embargo on all abstracts, including oral abstract, poster exhibition, e-poster and late breakers, will lift on Monday, 14 July 2025, at 15:30 Central African Time (CAT). If an abstract is part of an official IAS 2025 press conference that occurs before that time, the embargo on that abstract lifts at the start of the official press conference."

Combined doravirine and islatravir cooperate to inhibit NRTI and NNRTI resistant HIV-1 in vitro. (PubMed, Antiviral Res) - "MuSyC scores showed a negative correlation with doravirine FC values, number of NRTI mutations and presence of M184V/I, but not with islatravir FC values. Doravirine and islatravir may cooperatively inhibit NRTI and NNRTI resistant viruses despite complex mutational profiles, however the accumulation of resistance mutations may reduce the combinatorial activity."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018) (clinicaltrials.gov) - P3 | N=643 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

Switch to DOR/ISL (100/0.25 mg) QD From Oral ART: An Open-Label Phase III Study in Adults With HIV-1 (CROI 2025) - P3 | "MK-8591A-051 is a phase 3 study evaluating the efficacy and safety of switching from oral ART to DOR/ISL (100/0.25 mg), a once-daily single-tablet regimen...Conclusions Switching to DOR/ISL (100/0.25 mg) maintained viral suppression and was non-inferior to continuing bART at week 48. DOR/ISL was well tolerated with a similar safety profile to bART and did not adversely affect lymphocytes."

Clinical • Late-breaking abstract • P3 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Switch to DOR/ISL (100/0.25 mg) QD From BIC/FTC/TAF: A Blinded Phase III Study in Adults With HIV-1 (CROI 2025) - P3 | "MK-8591A-052 is an ongoing phase 3 study evaluating the efficacy and safety of switching from bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) to DOR/ISL (100/0.25 mg), a once-daily single-tablet regimen. Conclusions DOR/ISL (100/0.25 mg) maintained viral suppression and was non-inferior to BIC/FTC/TAF at week 48. DOR/ISL was well tolerated with a similar safety profile to BIC/FTC/TAF and did not adversely affect lymphocytes."

Clinical • Late-breaking abstract • P3 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Doravirine/islatravir (100/0.75 mg) once-daily compared to bictegravir/emtricitabine/tenofovir alafenamide as initial HIV-1 treatment: 48-week results from a phase 3, randomized, controlled, double-blind, non-inferiority trial. (PubMed, Clin Infect Dis) - P3 | "Doravirine/islatravir (100/0.75 mg) once-daily was non-inferior to bictegravir/emtricitabine/tenofovir alafenamide through week 48 for initial HIV-1 treatment. Due to decreases in CD4 and lymphocyte counts, development of this dose of doravirine/islatravir was stopped."

Head-to-Head • Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • CD4

Study of Doravirine/Islatravir (DOR/ISL 100 mg/0.75 mg) to Evaluate the Antiretroviral Activity, Safety, and Tolerability in Treatment-Naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020) (clinicaltrials.gov) - P3 | N=599 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

Doravirine/Islatravir for the treatment of HIV. (PubMed, Expert Opin Pharmacother) - "ISL doses as low as 0.25 mg proved non-inferior to current treatments. Therefore, evaluation of the long-term efficacy and safety of DOR/ISL should focus on reduced doses of ISL and minimizing CD4 reduction."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • CD4

A Study of Doravirine and Islatravir as a Single Entity or Combination Therapy and the Effect of Food in Healthy Adult Participants (MK-8591A-055) (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Merck Sharp & Dohme LLC

Combination therapy • New P1 trial

DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053) (clinicaltrials.gov) - P3 | N=500 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017) (clinicaltrials.gov) - P3 | N=672 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

The Effect of Pantoprazole on Doravirine/Islatravir Pharmacokinetics (IDWeek 2024) - No abstract available

PK/PD data • Infectious Disease

DOR/ISL in HIV-1 Antiretroviral Treatment-naïve Participants (MK-8591A-053) (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Nov 2026 ➔ Aug 2029

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

A Study of Doravirine/Islatravir (DOR/ISL, MK-8591A) for the Treatment of Human Immunodeficiency Virus 1 (HIV-1) Infection in Participants Who Previously Received DOR/ISL (MK-8591A-054) (clinicaltrials.gov) - P3 | N=650 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jan 2026 ➔ Sep 2028

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-052) (clinicaltrials.gov) - P3 | N=514 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2025 ➔ Aug 2028

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051) (clinicaltrials.gov) - P3 | N=501 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2025 ➔ Jul 2028

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

Challenges for novel antiretroviral development in an era of widespread TLD availability. (PubMed, Clin Infect Dis) - "We illustrate when generic TLD will become available worldwide and compare this with trial programmes and approval timelines for two case-study novel ART combinations: islatravir/doravirine and cabotegravir/rilpivirine. We demonstrate that currently these regimens and trial programmes will not meet key benchmarks required to compete with TLD."

Journal • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation

Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on antiretroviral therapy: 48-week results of a phase 3, randomised, open-label, non-inferiority trial. (PubMed, Lancet HIV) - P3 | "Switching to single-tablet doravirine (100 mg) and islatravir (0·75 mg) maintained viral suppression up to week 48 and was non-inferior to antiretroviral combinations used in clinical practice for adults with HIV-1; however, decreases in CD4 cell and total lymphocyte counts do not support further development of once-daily doravirine (100 mg) and islatravir (0·75 mg)."

Head-to-Head • Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease • Pain • CD4

Switch to fixed-dose doravirine (100 mg) with islatravir (0·75 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide: 48-week results of a phase 3, randomised, controlled, double-blind, non-inferiority trial. (PubMed, Lancet HIV) - P3 | "Switching to daily doravirine (100 mg) and islatravir (0·75 mg) was non-inferior to bictegravir, emtricitabine, and tenofovir alafenamide at week 48. However, decreases in CD4 cell and total lymphocyte counts do not support the further development of once-daily doravirine (100 mg) and islatravir (0·75 mg)."

Head-to-Head • Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease • Pain • CD4

Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017) (clinicaltrials.gov) - P3 | N=672 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Mar 2024 ➔ Nov 2024

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

Switching to Doravirine/Islatravir Maintains Viral Suppression Regardless of Archived Mutations (CROI 2024) - P3 | "Background: In 2 phase 3 clinical trials, switching to the 2-drug combination doravirine/islatravir (DOR/ISL) 100/0.75mg was non-inferior to continuing the prior antiretroviral (ART) regimen. Switching to DOR/ISL 100/0.75mg maintains viral suppression for up to 96 weeks regardless of archived M184I/V or NNRTI RAMs in proviral DNA."

Human Immunodeficiency Virus • Infectious Disease

Open-label, Follow-up of Doravirine/Islatravir (DOR/ISL 100 mg/0.75mg) for Participants With Human Immunodeficiency Virus-1 (HIV-1) Infection (MK-8591A-033) (clinicaltrials.gov) - P3 | N=2000 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2025 ➔ Oct 2027 | Trial primary completion date: Oct 2025 ➔ Oct 2027

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018) (clinicaltrials.gov) - P3 | N=643 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: May 2024 ➔ Feb 2025

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

A Study of Doravirine/Islatravir (DOR/ISL, MK-8591A) for the Treatment of Human Immunodeficiency Virus 1 (HIV-1) Infection in Participants Who Previously Received DOR/ISL (MK-8591A-054) (clinicaltrials.gov) - P3 | N=650 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Doravirine/Islatravir (DOR/ISL) in Heavily Treatment-Experienced (HTE) Participants for Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-019) (clinicaltrials.gov) - P3 | N=35 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease