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

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: May 2028 ➔ May 2029 | Trial primary completion date: May 2028 ➔ May 2029

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

Comparative Safety of B/F/TAF vs. Other Antiretroviral Therapy Regimens for Treatment-Experienced People With HIV-1: A Systematic Literature Review and Indirect Comparisons Using Multilevel Network Meta-Regression (ISPOR-EU 2025) - "Compared to B/F/TAF, ML-NMR results showed significantly greater decline in eGFR from baseline with dolutegravir/lamivudine (DTG/3TC) (mean difference [95% CrI]: -4.40 [-5.30, -3.51]) and DTG/abacavir/3TC (-3.60 [-5.74, -1.50]); change in eGFR was similar to DTG+F/TAF (-1.19 [-3.35, 1.06]). B/F/TAF demonstrated a more favorable renal safety profile compared to tenofovir-sparing DTG-based regimens, with similar all-cause discontinuation rates compared to other recommended ARTs, including DTG/3TC, and the investigational NRTI-sparing doravirine/islatravir. These findings support B/F/TAF as a renally safe and well-tolerated treatment option for TE PWH."

Clinical • Review • Human Immunodeficiency Virus • Infectious Disease

Evaluation of Fasting Lipids and Insulin Resistance After Switch to Doravirine/Islatravir (100 mg/0.25 mg) Once Daily: Week 48 Results From Two Randomized Phase 3 Studies in Adults Living With HIV-1 (EACS 2025) - P3 | "Purpose : In two Phase 3 studies, switching to doravirine/islatravir (DOR/ISL, 100 mg/0.25 mg), an investigational once-daily regimen for HIV treatment, demonstrated non-inferior efficacy and a comparable safety profile to continuing various baseline antiretroviral therapies (bART) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) at Week 48 (W48). Conclusions : Switching to DOR/ISL (100 mg/0.25 mg) had no clinically meaningful effect on fasting lipids and HOMA-IR at W48. Changes were comparable to continued bART or BIC/FTC/TAF."

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease

Weight and Body Composition After Switch to Doravirine/Islatravir (100 mg/0.25 mg) Once Daily from BIC/FTC/TAF in Adults Living With HIV-1: Week 48 Results From a Randomized, Double-Blind Phase 3 Study (EACS 2025) - P3 | "Conclusions : At W48, adults living with HIV-1 who switched to DOR/ISL (100 mg/0.25 mg) experienced minimal changes in weight and body composition. Changes were comparable to continued BIC/FTC/TAF."

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease

Efficacy and safety of doravirine/islatravir in heavily treatment-experienced participants living with HIV-1 from a randomized trial. (PubMed, AIDS) - P3 | "DOR/ISL plus OBT improved HIV-1 suppression in HTE adults living with HIV-1 and was generally well tolerated."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

A Study of Doravirine/Islatravir in Healthy Lactating Females (MK-8591A-061) (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open

Efficacy and Safety by Sex Assigned at Birth After Switch to Doravirine/Islatravir (100 mg/0.25 mg) Once Daily: Week 48 Results from Two Phase 3 Randomized, Active-Controlled Studies in Adults Living with HIV-1 (IDWeek 2025) - No abstract available

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease

Safety and Efficacy of Doravirine/Islatravir (DOR/ISL) 100/0.25 mg Once Daily (QD) after ISL Dose Reduction from 0.75 mg: Week 48 Results from an Open-Label Phase 3 Study (IDWeek 2025) - No abstract available

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease

Efficacy and Safety by Age After Switch to Doravirine/Islatravir (100 mg/0.25 mg) Once Daily: Week 48 Results from Two Phase 3 Randomized, Active-Controlled Studies in Adults Living with HIV-1 (IDWeek 2025) - No abstract available

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease

Switching to Doravirine/Islatravir (100 mg/0.25 mg) Once Daily Maintains Viral Suppression Through Week 48 in the Presence of Archived NNRTI Resistance-Associated Mutations or M184I/V in Proviral DNA (IDWeek 2025) - No abstract available

Human Immunodeficiency Virus • Infectious Disease

U.S. FDA Accepts New Drug Application for Merck’s Doravirine/Islatravir, an Investigational, Once-Daily, Oral, Two-Drug Regimen for Treatment of Adults with Virologically Suppressed HIV-1 Infection (Businesswire) - "Merck...announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for doravirine/islatravir (DOR/ISL), an investigational, once-daily, oral, two-drug regimen for adults with HIV-1 infection that is virologically suppressed on antiretroviral therapy. The FDA has set a target action date of April 28, 2026, for the application under the Prescription Drug User Fee Act (PDUFA)...The NDA is based on findings at Week 48 of two pivotal Phase 3 clinical trials (MK-8591A-051 and MK-8591A-052)..."

FDA filing • PDUFA • Human Immunodeficiency Virus • Infectious Disease

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) - P3 | "BACKGROUND: In three Phase 3 studies (P051: NCT05631093; P052: NCT05630755; P054: NCT05766501) virologic suppression was maintained in people living with HIV who switched to doravirine/islatravir (DOR/ISL 100 mg/0.25 mg); 2 studies (P051 and P052) were comparative and demonstrated noninferiority to baseline antiretroviral therapy (bART) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Switching to DOR/ISL 100 mg/0.25 mg in Phase 3 clinical studies maintained viral suppression for at least 48 weeks in the presence of preexisting M184I/V in proviral DNA."

Human Immunodeficiency Virus • Infectious Disease

A Study of Doravirine/Islatravir in Healthy Lactating Females (MK-8591A-061) (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

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 2027 ➔ May 2028 | Trial primary completion date: Oct 2027 ➔ May 2028

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

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