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

Development and Preclinical Evaluation of a Dual-Drug Implant for Long-Acting HIV Prevention and Contraception. (PubMed, Pharmaceutics) - "We developed a long-acting (LA) implant for the simultaneous and sustained delivery of the antiretroviral islatravir (ISL) and the contraceptive hormone etonogestrel (ENG)...Implants across all groups were well tolerated and demonstrated favorable local tolerability over the 90-day dosing period. Integration of multiple indications into a single platform capable of sustained release over an extended duration holds potential to address persistent gaps in women's sexual and reproductive health needs."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease • Long-acting Reversible Contraceptives • Women's Health

M184V: The Major Determinant of Cooperative ISL Resistance When in Combination with Multiple TAM2 Mutations in HIV-1 Subtype C. (PubMed, Viruses) - "Contrary to the well-documented antagonism between M184V and TAMs in zidovudine resistance, these two resistance pathways exhibit cooperative rather than antagonistic interactions in the context of ISL resistance. Importantly, elucidating the mechanistic basis of M184V-TAM2 cooperation would establish a more predictive framework for understanding how complex resistance mutation patterns impact ISL susceptibility and guide treatment decisions in virologically experienced individuals. Considering the diminished use of TAM2-seletive antiretroviral drugs in contemporary ART regimens, islatravir is likely to be an effective treatment option."

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) (clinicaltrials.gov) - P2/3 | N=570 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Apr 2030 ➔ Dec 2031

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

Exposure-Response Analysis of Islatravir 0.25 mg With Doravirine 100 mg Once Daily in Treatment-Naive and Virologically Suppressed People Living With HIV-1 at Week 48 (IDWeek 2026) - No abstract available

Human Immunodeficiency Virus • Infectious Disease

Switching to Islatravir + Ulonivirine Once Weekly Maintained HIV-1 Viral Suppression at Week 24 in the Presence of Baseline NNRTI Resistance-Associated Mutations and M184I/V in Proviral DNA (IDWeek 2026) - No abstract available

Human Immunodeficiency Virus • Infectious Disease

Patient-Reported Outcomes From Virologically Suppressed Adults Living With HIV-1 Switching to Once-Weekly Oral Islatravir in Combination With Ulonivirine: Phase 2b Week 24 Results (IDWeek 2026) - No abstract available

Clinical • Combination therapy • P2b data • Patient reported outcomes • Human Immunodeficiency Virus • Infectious Disease

Allosteric Crosstalk between Inhibitor Binding Sites Drives Enhanced Islatravir Susceptibility in F227C HIV-1 Reverse Transcriptase. (PubMed, ACS Infect Dis) - "Doravirine (DOR) and islatravir (ISL) are inhibitors of human immunodeficiency virus type 1 (HIV-1) replication that block the viral reverse transcriptase (RT) by distinct mechanisms...Here, we report cryoEM structures of islatravir triphosphate (ISL-TP) bound to wild-type (WT) RT and F227C RT. Comparison with the corresponding ISL-TP and dATP-bound WT RT structures reveals that the F227C mutation induces an unexpected conformational change in a loop of the palm domain that is positioned to gate substrate access, providing a structural basis for ISL hypersusceptibility."

Journal • Human Immunodeficiency Virus • Infectious Disease

An optimized product-enhanced reverse transcriptase assay for sensitive and quantitative detection of HIV viral load and phenotypic drug resistance. (PubMed, J Clin Microbiol) - "We demonstrated the assay's feasibility for phenotypic DRT using lamivudine-5'-triphosphate (3TC-TP)-to which the M184V mutation confers high-level resistance-and quantified 3TC-TP inhibition using the difference in cDNA produced between drug and no-drug conditions...Finally, we showed that PERT could detect resistance to existing and emerging RT inhibitors, including tenofovir-diphosphate (TFV-DP), doravirine (DOR), and islatravir (ISL)-TP.IMPORTANCEAlthough antiretroviral therapy can effectively treat and prevent HIV infection, treatment efficacy and global control of the HIV epidemic are threatened by rising rates of HIV drug resistance...Our optimized product-enhanced reverse transcriptase (PERT) assay for simultaneous viral load and phenotypic drug resistance quantification is fast (~2 h), sensitive, and accurate. We can also leverage existing RT-qPCR instruments used for viral load measurement to significantly improve access to HIV drug resistance..."

Journal • Human Immunodeficiency Virus • Infectious Disease

Clinical Resistance to Lenacapavir During Treatment of HIV Infection: A Review. (PubMed, Viruses) - "In contrast, no cases of viral rebound with resistance to LEN have been observed in virologically suppressed PWH switching to the once-daily single-tablet regimen (STR) combining LEN with the integrase strand-transfer inhibitor (INSTI) bictegravir after up to 48 weeks in two Phase 3 studies, and for >3 years in Phase 2. Similarly, no resistance to LEN has been observed after up to 96 weeks in the Phase 2 study of once-weekly regimen of the deoxyadenosine analog RT inhibitor islatravir + LEN...Overall, resistance to LEN in regimens using synchronous dosing (daily or weekly oral, or 6-monthly injectable) has been rare in clinical studies. As the use of LEN is predicted to increase in the near future with these potential new combinations, capabilities to test for capsid resistance are being developed through global commercial options as well as through regional health institutions."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease

Dose-ranging pharmacokinetics, safety, and efficacy of a 90-day intravaginal ring delivering islatravir in pigtail macaques. (PubMed, Sci Adv) - "In a challenge study involving 12 weekly low-dose vaginal exposures to SHIV162p3, six macaques treated with 60-milligram ISL IVRs for 90 days remained seronegative and SHIV RNA negative, while two untreated controls were infected. These data provide initial preclinical evidence that a 90-day extended-release ISL IVR is safe and offers complete protection in a stringent challenge model, warranting further clinical investigation."

Journal • PK/PD data

Once-weekly oral islatravir plus lenacapavir: clinical considerations for individualized use. (PubMed, J Acquir Immune Defic Syndr) - "Rather than reflecting shortcomings of early-phase evaluation, the key questions now relate to the regimen's future clinical use, including its pharmacokinetic and virological forgiveness after delayed or missed doses, optimal hepatitis B virus (HBV) screening, vaccination, and monitoring when switching to a regimen without HBV-active agents, and the clinical relevance of drug-drug interactions in the setting of polypharmacy. Addressing these issues will help inform individualized treatment decisions, counseling, and clinical monitoring as the regimen advances through clinical development and, potentially, into routine clinical practice."

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

Switch to once-weekly, single-tablet islatravir-lenacapavir from daily standard of care for HIV-1 (ISLEND-2): a multicentre, randomised, open-label, active-controlled, phase 3 non-inferiority trial. (PubMed, Lancet) - P3 | "Once-weekly islatravir-lenacapavir showed non-inferior efficacy to the standard of care and was generally well tolerated. Longer-term safety data will provide further valuable insights beyond the week 48 data presented here. Islatravir-lenacapavir has potential to be the first once-weekly complete oral single-tablet regimen for HIV-1 treatment."

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

Phase 3 Trial of Weekly Oral Islatravir-Lenacapavir for HIV-1 Treatment. (PubMed, N Engl J Med) - P3 | "Among persons with virologically suppressed HIV-1, once-weekly oral ISL/LEN was noninferior to once-daily B/F/TAF in maintaining HIV viral load suppression. (Funded by Gilead Sciences and Merck Sharp and Dohme; ISLEND-1 ClinicalTrials.gov number, NCT06630286.)."

Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Mitigating intellectual property barriers to HIV and comorbidities treatment in Eurasian Patent Organization countries: programme results and policy implications (AIDS 2026) - "The drugs included tenofovir/emtricitabine (Armenia, Russia), rilpivirine (Russia), long-acting rilpivirine, islatravir, lenacapavir (EAPO); sofosbuvir (Russia); molnupiravir (EAPO, Russia), nirmatrelvir (EAPO); pretomanid in bedaquiline/pretomanid/linezolid regimen, pretomanid granulate, pretomanid amorphous form (EAPO), bedaquiline (Belarus, Kazakhstan, Kyrgyzstan). EECA communities developed expertise on patent challenges, successfully opposed patents, and revealed and addressed systemic barriers to CSO engagement in access-related IP work. The programme has potential for expansion, as demonstrated by a CBO opposition in Uzbekistan in December 2025 (delamanid). Results from the structural barrier analysis call for legal reform to enhance community involvement in mitigating IP barriers and improving access to medicines."

Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Tuberculosis

A rapid and inexpensive phenotypic assay for measuring resistance to existing and emerging HIV drugs (AIDS 2026) - "We measured inhibition of HIV-RT activity (viral load ~2500) by the nucleoside RT inhibitor lamivudine-5’-triphosphate (3TC-TP), nucleoside RT translocation inhibitor MK-8591-TP, and non-nucleoside RT inhibitors doravirine and rilpivirine. This PERT assay meets WHO analytical sensitivity requirements for DRT. With its high sensitivity, short duration (~2 hours), compatibility with existing and emerging RT inhibitors, and ability to leverage existing instruments in high- and low-resource settings, this enzymatic assay has the potential to significantly improve access to routine HIV DRT in point-of-care and clinical trial settings."

Human Immunodeficiency Virus • Infectious Disease

Determining Critical Physiological and Drug Specific Parameters for Enhancing a Physiologically Based Pharmacokinetics Model for the Female Reproductive Tract. (PubMed, Pharmaceutics) - " Our work was conducted to help fill this critical gap, evaluating four model drugs with diverse physicochemical and transporter profiles, dapivirine (DPV), levonorgestrel (LNG), MK-2048, and 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA; also known as islatravir or MK-8591) in in vitro and ex vivo human models. Collectively, these findings demonstrate the interplay among solubility, matrix-specific binding, and tissue permeability in governing local drug distribution within the FRT. The experimentally derived parameters provide quantitative inputs for FRT PBPK model development, and are expected to inform design of safe and effective localized therapies for women's reproductive health."

Journal • PK/PD data

Improving transparency on patenting strategies of HIV medicines candidates to anticipate access challenges (AIDS 2026) - " Based on monitoring of clinical trials for new HIV antiretrovirals (ARVs), the following compounds were selected: GS-1614; GS-6212; GS-5894; GS-4182; GS-1720, VH4011499; VH4004280; VH4367310; VH-310; VH4524184; MK-8527; MK-850, islatravir... The findings have shown the multiple patenting on key antiretrovirals – reflecting the evergreening strategy - and an initial patent filing for newer compounds, allowing national-level monitoring by MMA members, and anticipating patent applications to be challenged. However, the lack of transparency of chemical structures has hindered the ability to develop an accurate patent landscape, which is an access challenges to promising candidates in the drug pipeline."

Human Immunodeficiency Virus • Infectious Disease

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 (AIDS 2026) - P2 | "BACKGROUND: The ongoing MK-8591B-060 study evaluates the nucleoside reverse-transcriptase translocation inhibitor (NRTTI) ISL combined with the non-nucleoside reverse-transcriptase inhibitor (NNRTI) ULO as oral, once-weekly treatment in virologically suppressed people living with HIV-1. ISL+ULO maintained a high rate of confirmed virologic suppression through W24, with efficacy comparable to BIC/FTC/TAF. ISL+ULO was generally well-tolerated; no safety concerns were identified."

Clinical • Late-breaking abstract • P2b data • Human Immunodeficiency Virus • Infectious Disease • CD4

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 (AIDS 2026) - P3 | "ISL/LEN was efficacious and well tolerated and has the potential to be the first complete once-weekly oral single-tablet treatment regimen for HIV-1. Funding: Gilead Sciences, Inc. and Merck Sharp & Dohme LLC."

Clinical • Late-breaking abstract • P3 data • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4

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 (AIDS 2026) - P3 | "ISL/LEN was noninferior to B/F/TAF, with no virologic failures at W48, and was well tolerated. ISL/LEN has the potential to be the first complete once-weekly oral single-tablet treatment regimen for virologically suppressed PWH. Funding: Gilead Sciences, Inc."

Clinical • Late-breaking abstract • P3 data • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4

Patent evergreening on long-acting HIV technologies (AIDS 2026) - " Based on oversight of clinical trials and regulatory approvals, the following compounds were selected: lenacapavir (LEN), cabotegravir (CAB), rilpivirine (RIL), islatravir (ISL) and MK-8527. The findings reveal that companies and academic institutions are pursuing patent protection for long-acting HIV technologies, with potential to extend or establish a monopoly over them. This will delay market entry of generics in countries where these applications are filed and granted. The potential public health benefits of these technologies should be addressed, including through use of TRIPS flexibilities, such as patent oppositions, compulsory licences and a public health perspective for patent examination."

Human Immunodeficiency Virus • Infectious Disease

Features of HIV-1 acquisition in adults receiving pre-exposure prophylaxis as part of the IMPOWER-22 and IMPOWER-24 open-label phase (AIDS 2026) - P3 | " Islatravir 60 mg oral once-monthly, compared with daily FTC/TDF or FTC/TAF as PrEP, was evaluated in cisgender women (randomized 1:1; IMPOWER-22, NCT04644029) and transgender women and men who have sex with men (randomized 2:1; IMPOWER-24, NCT04652700). No clear evidence of LEVI was found; delays between viremia detection and seroconversion generally followed expected patterns of natural infection, with no evidence of antibody-antecedent low-level viremia characteristic of LEVI."

Clinical • Human Immunodeficiency Virus • Infectious Disease

Advancing a multi-year subdermal antiretroviral delivery implant towards clinical assessment for HIV pre-exposure prophylaxis, treatment and multipurpose prevention (AIDS 2026) - "Leveraging previous NanoDDI data demonstrating 29 months of sustained islatravir (ISL) delivery and 100% preventive efficacy in non-human primates (NHPs), we expanded the platform to deliver MK-8527, lenacapavir (LEN), bictegravir (BIC), tenofovir alafenamide (TAF), and levonorgestrel (LNG) for clinical translation in PrEP, treatment, and multipurpose prevention. NanoDDI provides multi-year long ARV delivery, maintaining protective levels and showing efficacy against SHIV in NHPs. This technology is now being advanced for first-in-human studies."

Clinical • First-in-human • Human Immunodeficiency Virus • Infectious Disease • Inflammation • NLRP3

Switching INSTI-based to doravirine-based ART with TAF/FTC reduces ex vivo molecular signatures of atherogenesis in people with HIV (AIDS 2026) - P1 | "BACKGROUND: Antiretroviral therapy (ART), such as bictegravir and tenofovir alafenamide (B/F/TAF), containing the combination of Integrase Inhibitors (INSTI) and TAF, are linked to weight gain and lipid abnormalities that increase the risk for future atherosclerotic cardiovascular disease (CVD). Switching from INSTI-based B/F/TAF to DOR-based DOR/F/TAF in PLWH with weight gain and dyslipidemia resulted in at least a 35% relative decrease in key early atherogenesis mechanisms (TEM and MDFCF) in a mechanistic ex vivo assay of atherogenesis. These changes within each individual could be attributed solely to DOR, as the backbone of ART (F/TAF) remained unchanged. Larger studies in PLWH using DOR-based ART, such as DOR/islatravir compared to Dolutegravir (DTG) + Lamivudine (3TC) and B/F/TAF, are needed to determine whether INSTI-TAF-induced cardiometabolic toxicity can be reversed by switching to DOR."

Preclinical • Atherosclerosis • Dyslipidemia • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • ITGAM

Alimatrevir: Mass production for $3 per year (AIDS 2026) - "BACKGROUND: Merck MK-8527 is a nucleoside reverse transcriptase translocation inhibitor (NRTTI), similar in structure to islatravir. The NRTTI MK-8527 could be mass produced for only $15ppy. Low unit prices could allow highly cost-effective mass distribution of MK-8527 as PrEP in LMICs for significantly less than either oral generic TDF/FTC or long-acting lenacapavir (both currently $40/year). Monthly MK-8527 could also offer important delivery advantages over daily oral or injectable formulations, particularly in resource-constrained settings."