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

Oral Islatravir in Macaques Decreases Lymphocytes and Monocytes and Is Associated with Immune Alterations. (PubMed, Pharmaceutics) - "This effect was reversed after treatment cessation as observed in humans. Our results highlight the value of the macaque model to study immune alterations at the preclinical stage."

Journal • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD20 • CD4 • CD8

Resistance Analysis of Weekly Islatravir Plus Lenacapavir in People with HIV at 48 Weeks. (PubMed, J Acquir Immune Defic Syndr) - "ISL+LEN maintained high rates of VS, including in one participant with pre-existing M184V. No participants developed drug resistance. These findings support the ongoing evaluation of QW oral ISL+LEN for HIV-1 treatment."

Journal • Human Immunodeficiency Virus • Infectious Disease

Development of a melt-cast microneedle patch for sustained drug release of islatravir. (PubMed, J Pharm Sci) - "The MNPs demonstrated a sustained release of islatravir with roughly first-order release kinetics ∼40 days in vitro. We conclude that MNPs made with a simple melt-casting process can enable prolonged drug release for HIV treatment/PrEP, contraception, and other therapeutic applications."

Journal • Human Immunodeficiency Virus • Infectious Disease

Safety and Tolerability of Oral Islatravir Once Monthly as Pre-Exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study. (PubMed, Clin Infect Dis) - P3 | "Islatravir qm was generally well-tolerated; decreases in total lymphocytes were observed with islatravir. Original primary efficacy objectives were not assessed due to early study stoppage."

Journal • P3 data • Gastroenterology • Gastroesophageal Reflux Disease • Human Immunodeficiency Virus • Infectious Disease

Islatravir distribution in plasma, peripheral blood mononuclear cells, and mucosal tissues after monthly oral dosing. (PubMed, AIDS) - P2 | "The favorable tissue distribution of islatravir and islatravir-triphosphate following oral administration supports the evaluation of NRTTIs for HIV-1 pre-exposure prophylaxis."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease

Computational Validation of a Clinical Decision Support Algorithm for LAI-PrEP Bridge Period Navigation at UNAIDS PrEP Target Scale (21.2 Million Individuals). (PubMed, Viruses) - "The tool demonstrates predictive validity with policy-grade statistical precision. Using published epidemiologic parameters (HIV incidence 2-5% among indicated users, LAI-PrEP efficacy 96%), our model translates the 4.1 million additional successful transitions into approximately 80,000-100,000 prevented HIV infections annually (midpoint: 100,000), corresponding to an estimated USD 40 billion in averted lifetime treatment costs."

Journal • Human Immunodeficiency Virus • Infectious Disease

A clinical study of islatravir and ulonivirine for people with HIV-1 who have not been treated before (MK-8591B-062) (clinicaltrialsregister.eu) - P2/3 | N=35 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2/3 trial • Human Immunodeficiency Virus • Infectious Disease • CD4

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. (PubMed, Lancet HIV) - "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."

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

A Clinical Study of Islatravir and Ulonivirine for People With HIV-1 Who Have Not Been Treated Before (MK-8591B-062) (clinicaltrials.gov) - P2/3 | N=570 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial primary completion date: Oct 2029 ➔ Apr 2029

Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

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. (PubMed, Lancet) - P3 | "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."

Clinical • Head-to-Head • Journal • P3 data • Hepatitis B • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4

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. (PubMed, Lancet) - P3 | "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."

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

Study Evaluating the Safety and Efficacy of Islatravir in Combination With Lenacapavir in Virologically Suppressed People With HIV (clinicaltrials.gov) - P2 | N=142 | Active, not recruiting | Sponsor: Gilead Sciences | Trial completion date: Nov 2027 ➔ Mar 2028

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

A subcutaneous implant that releases islatravir provides long-lasting protection against vaginal SHIV infection in macaques. (PubMed, J Control Release) - "The ISL implants were well-tolerated in macaques and showed no signs of ISL-induced lymphopenia over the 8-month dosing period. These findings support the clinical development of the PCL implant as a safe and effective long-acting drug delivery of ISL or other NRTTIs for long-acting HIV PrEP in women."

Journal • Human Immunodeficiency Virus • Infectious Disease • Vaginitis

Standardisation of monitoring routines for new long-acting antiretrovirals in development. (PubMed, Lancet HIV) - "The US Food and Drug Administration's clinical hold on Gilead Sciences' once-weekly combination of GS-1720 and GS-4182 due to unexpected CD4 T-cell and lymphocyte count declines represents a key safety signal in long-acting HIV therapy development. This event parallels the earlier islatravir trials, in which similar immunological effects led to a downsized development programme with lower doses of the drug...As GS-4182 is a prodrug that converts to lenacapavir, the parent compound warrants careful evaluation, particularly given lenacapavir's anticipated widespread use for HIV prevention...Future trials should implement standardised monitoring protocols with individual participant trajectories, predefined decline thresholds, and clear discontinuation criteria. As long-acting antiretroviral therapy advances, maintaining rigorous immunological surveillance becomes essential to balance dosing convenience against potential immunological risks."

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

Pediatric human immunodeficiency virus infection in the modern era: A systematic review of recent advances and their implications. (PubMed, Pediatr Investig) - "Long-acting injectable therapies, such as cabotegravir/rilpivirine and investigational agents like lenacapavir and islatravir, show promise for adolescents. Advances in pediatric HIV care are substantial but uneven. Continued investment in age-appropriate therapies, psychosocial support, and implementation research is essential to close persistent gaps and ensure equitable, lifelong care for children and adolescents living with HIV."

Journal • Review • Cardiovascular • Cognitive Disorders • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Once-Weekly Oral Islatravir Plus Lenacapavir Versus Daily Oral Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Persons With HIV-1 : A Phase 2 Randomized Study. (PubMed, Ann Intern Med) - P2 | "Once-weekly oral ISL+LEN maintained high rates of virologic suppression through week 48 and was not associated with any treatment-related grade 3 or greater or serious AEs. Gilead Sciences, Inc."

Journal • P2 data • Human Immunodeficiency Virus • Infectious Disease • CD4

A Clinical Study of Islatravir and Ulonivirine for People With HIV-1 Who Have Not Been Treated Before (MK-8591B-062) (clinicaltrials.gov) - P2/3 | N=570 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Balancing Pharmacokinetic Targets and Lymphocyte Declines With Once-Monthly Oral Islatravir for PrEP. (PubMed, J Infect Dis) - No abstract available

Journal • PK/PD data

A Clinical Study of Islatravir and Ulonivirine for People With HIV-1 Who Have Not Been Treated Before (MK-8591B-062) (clinicaltrials.gov) - P2/3 | N=570 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2/3 trial • Human Immunodeficiency Virus • Infectious Disease

Oral Weekly Islatravir Plus Lenacapavir in Virologically Suppressed People with HIV-1: 96 Week Outcomes from a Phase 2 Study (EACS 2025) - P2, P3 | "Method : In this randomized, open-label, active-controlled Phase 2 study, VS adults on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) were randomized 1:1 to ISL 2 mg plus LEN 300 mg once weekly (n=52) or to continue daily B/F/TAF (n=52). These results support ISL+LEN as a potential first complete once-weekly oral regimen for HIV-1. Two Phase 3 studies (ISLEND-1, NCT06630286; ISLEND-2, NCT06630299) are ongoing."

Late-breaking abstract • P2 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Patient-Reported Outcomes From People With HIV-1 Receiving Once-Weekly Oral Islatravir in Combination With Lenacapavir: Phase 2 Week 48 Results (EACS 2025) - P2 | "Method : PWH were randomized to QW oral ISL+LEN or to continue QD oral bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). For HIV-PP-RC, 65.4% of ISL+LEN participants reported prior regimen was more burdensome; 69.2% were more/much more satisfied with current regimen. ​ Conclusions : We observed similar health status between groups; however, participants receiving QW oral ISL+LEN reported higher treatment satisfaction, better lifestyle fit, reduced reminder of HIV status, and less burden/worry, suggesting some PWH prefer QW over QD regimens."

Clinical • Combination therapy • P2 data • Patient reported outcomes • Human Immunodeficiency Virus • Infectious Disease

A Study of Islatravir (ISL) and Ulonivirine (ULO) Once Weekly (QW) in Virologically Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) (MK-8591B-060) (clinicaltrials.gov) - P2 | N=150 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Sep 2027 ➔ Sep 2031

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

Kinetic Insights into the Enhanced Antiviral Activity of Islatravir against Doravirine Resistance-Associated Substitution Mutations in HIV-1 Reverse Transcriptase. (PubMed, Biochemistry) - "Alongside this, the F227C mutation decreased dATP's binding affinity with both templates. Our data established a kinetic basis for the published cell-based resistance selection assay results, underscoring the significant potential of the ISL/DOR combination therapy in treating HIV-1 infected patients."

Journal • Human Immunodeficiency Virus • Infectious Disease

Population Pharmacokinetic Analysis of Islatravir and the Impact of Intrinsic Factors in Participants with HIV-1 (IDWeek 2025) - No abstract available

Clinical • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Modeling Confirms Islatravir 0.25 mg Administered Daily Has No Adverse Effect on Total Lymphocyte or CD4+ T-cell Counts in People Living with HIV (IDWeek 2025) - No abstract available

Adverse events • Human Immunodeficiency Virus • Infectious Disease • CD4