Tybost (cobicistat) / Gilead - LARVOL DELTA

Safety and efficacy of the novel BRAF inhibitor FORE8394 in patients with advanced solid and CNS tumors: Results from a phase 1/2a study. (ASCO 2023) - P1/2 | " In a phase 1/2a study, patients (pts) aged ≥3 years with BRAF-altered, advanced solid or CNS tumors received FORE8394 (900-3600 mg/day or mg/m2 dosing) with or without a pharmacokinetic booster (cobicistat 150 mg/day). As single agent anticancer therapy, FORE8394 had antitumor activity in various tumors with BRAF alterations, including pts previously treated with MAPKi and pts with BRAF fusions. Durable tolerability was observed, and TEAEs indicative of paradoxical MAPK activation were not observed, consistent with the novel mechanism of action of FORE8394. These results support further evaluation of FORE8394."

Clinical • Metastases • P1/2 data • Brain Cancer • Cardiovascular • CNS Disorders • CNS Tumor • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Glioma • Heart Failure • Langerhans Cell Histiocytosis • Melanoma • Ocular Inflammation • Oncology • Ophthalmology • Ovarian Cancer • Retinal Disorders • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • Uveitis • AGK • BRAF

Pharmacological boosting of azacitidine/venetoclax in acute myeloid leukemia. (PubMed, Blood Neoplasia) - P2 | "Azacitidine/venetoclax is the standard treatment for patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy. The potentiated antileukemic activity positions cobicistat as a promising complementary agent in AML therapy. This trial was registered at www.clinicaltrials.gov as NCT06014489."

Clinical • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CYP3A4

Comparative and Subtractive Genomics Analysis of Multidrug-Resistant Klebsiella pneumoniae Strains for Novel Target Identification and Drug Repurposing Strategies. (PubMed, Int J Microbiol) - "Subsequent molecular dynamics simulations, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), hydrogen-bond occupancy, principal component analysis (PCA), and PCA-based free energy landscape (FEL) analyses, consistently identified tenapanor, micafungin, deferoxamine, and cobicistat as the most stable protein-ligand complexes, with tenapanor exhibiting the most favorable overall structural and thermodynamic stability profile. These findings identify accD as a promising therapeutic target in MDR K. pneumoniae and suggest several FDA-approved compounds as potential candidates for drug repurposing. Although experimental validation is needed to confirm their biological activity and therapeutic potential, this study demonstrates the potential of integrating comparative genomics with molecular dynamics analyses to support antimicrobial target identification and drug repurposing against MDR bacterial pathogens."

Journal • Infectious Disease • Pneumonia

Pharmacokinetic Properties of Antiretroviral and Anti-Tuberculosis Drugs During Pregnancy and Postpartum (clinicaltrials.gov) - P=N/A | N=205 | Terminated | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Completed ➔ Terminated; The study was closed to accrual early based on Study Monitoring Committee review indicating that the study objectives had either been achieved or could not be met within a reasonable timeframe for the then-open arms.

Trial termination • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Targeting MEST using cobicistat as a therapeutic strategy for gastric cancer through suppressing NF-κB signaling. (PubMed, Front Oncol) - "MEST functions as a key oncoprotein driving GC progression via NF-κB activation. Cobicistat, a candidate MEST-inhibitory compound, exhibits favorable preclinical efficacy and safety, providing a promising candidate for targeted GC therapy."

Journal • Gastric Cancer • Oncology • Solid Tumor

A Study to Provide Continued Access to Study Drug to Children and Adolescents Who Have Completed Clinical Studies Involving Gilead HIV Treatments (clinicaltrialsregister.eu) - P4 | N=290 | Sponsor: Gilead Sciences, Inc.

New P4 trial • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Resuppression and resistance after confirmed virologic failure among women on CAB+RPV LA in the OPERA Cohort (AIDS 2026) - "Summary of resistance in the 7 women who experienced CVF on CAB+RPV LA Woman who experienced CVF on CAB+RPV LA VL at Start (c/mL ) BMI at Start (kg/m 2 ) Months to CVF M onths to Resuppression a Regimen when Resuppressed a Summary of Resistance #1 20 25.1 1.6 5.5 CAB+RPV LA Multiple polymorphisms before and during CAB+RPV LA; no resistance to CAB or RPV at CVF; resuppressed on CAB+RPV LA through study end #2 < 20 49.6 7.4 2.9 DRV/c/FTC/TAF Partial resistance to NNRTIs other than RPV before CAB+RPV LA; resistance to CAB and RPV at CVF #3 30 36.6 9.2 5.7 BIC/FTC/TAF GenoSure Archive prior to CAB+RPV LA had insufficient sample; no further testing done; resuppressed through study end on B/F/TAF #4 35,500 18.3 9.1 N/A b N/A b Multiple polymorphisms before CAB+RPV LA; resistance to CAB and RPV after CVF #5 < 20 27.8 15.3 15.6 DRV/c/FTC/TAF + LEN No resistance tests prior to CAB+RPV LA; multiple polymorphisms during CAB+RPV LA; LLV until 3 rd regimen post CVF #6 < 20..."

Clinical • Human Immunodeficiency Virus • Infectious Disease

Cystobactamid off-target profiling reveals favorable safety, superoxide reduction, and SCARB1 inhibition in eukaryotes. (PubMed, NPJ Drug Discov) - "Metabolism studies revealed glucuronidation and amide bond hydrolysis as key pathways, whereby cystobactamid metabolic stability substantially improved by cobicistat co-treatment. Affinity-based protein profiling identified the cholesterol- and HCV-receptor scavenger receptor class B member 1 (SCARB1) as a primary eukaryotic off-target protein, with cystobactamids shown to inhibit SCARB1´s function, preventing hepatitis C virus pseudoparticle entry into cells. These findings suggest a high therapeutic potential for cystobactamids and highlight SCARB1 as a primary eukaryotic target."

Journal • Cardiovascular • Hepatitis C • Infectious Disease • Inflammation • SCARB1

A precautionary tale of lenacapavir drug-drug interactions: A case series of two persons living with HIV receiving long-acting injections. (PubMed, Int J STD AIDS) - "Case 1 describes a PLWH prescribed clopidogrel after an acute cerebrovascular event receiving an antiretroviral (ARV) regimen including subcutaneous lenacapavir and ibalizumab biweekly infusions...Case 2 is a highly treatment experienced PLWH prescribed an ARV regimen including subcutaneous lenacapavir and intramuscular cabotegravir/rilpivirine injections on concomitant inhaled and nasal fluticasone...The electronic medical record alerts were customized to note these possible lenacapavir drug-drug interactions, similar to protease inhibitors/pharmacokinetic boosters (ritonavir and cobicistat) to prevent future events. This case series highlights possible lenacapavir drug-drug interactions and is a precautionary tale to other institutions to consider customizing electronic medical alerts for this novel long-acting injection."

Journal • Endocrine Disorders • Human Immunodeficiency Virus • Infectious Disease • Nephrology • Renal Disease

When Local Isn't Local: Systemic Complications from Intra-Articular Steroids in A Patient on Cobicistat (ENDO 2026) - "Cobicistat is a pharmacokinetic enhancer in the combined antiretroviral formulation Symtuza® (darunavir, cobicistat, emtricitabine, tenofovir alafenamide), which is commonly used to treat HIV...He then presented to the ED with bilateral multi-segmental pulmonary embolism treated with apixaban...Antiretroviral treatment was then switched to Biktrvy® (bictegravir/ emtricitabine/ tenofovir)...In this case the cobicistat- glucocorticoid interaction appears to have caused glucocorticoid excess leading to insomnia, hypomanic behavior and possibly pulmonary embolism followed by adrenal insufficiency. Given the widespread use of inhaled and injectable steroids by patients who can also be receiving cobicistat, early recognition of this interaction can potentially prevent complications related to glucocorticoid excess and adrenal insufficiency."

Clinical • Cardiovascular • CNS Disorders • Endocrine Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Insomnia • Nephrology • Osteoarthritis • Pulmonary Embolism • Renal Disease • Respiratory Diseases • Sleep Disorder

MON-887 - A Case of Genvoya Induced Cushing Syndrome (ENDO 2026) - "Introduction: Boosted antiretroviral therapy is widely used in HIV management, the two boosting agents being ritonavir and cobicistat...The findings were consistent with iatrogenic Cushing syndrome due to elevated systemic fluticasone levels from cobicistat-mediated CYP3A4 inhibition. Genvoya was discontinued and replaced with Biktarvy, allowing continuation of fluticasone. Physiologic hydrocortisone replacement was initiated...Although recognized in the literature, this interaction can still sometimes be missed, especially since the booster is co-formulated within a single tablet, resulting in delayed diagnosis and preventable morbidity. Early recognition, adjustment of antiretroviral therapy and or co-administered drugs, and monitoring for secondary adrenal insufficiency are essential for safe management."

Clinical • Late-breaking abstract • Asthma • Cushing’s Disease • Endocrine Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Nephrology • Renal Disease • Respiratory Diseases

Prescription of colchicine and NSAIDs for acute gout flares in severe chronic kidney disease and colchicine in major drug–drug interactions: evidence from an electronic health-record based gout register (EULAR 2026) - "Strong inhibitors included atazanavir, clarithromycin, cobicistat, darunavir, fluconazole, ketoconazole, lopinavir, ritonavir, nirmatrelvir–ritonavir, voriconazole, and ciclosporin. Moderate to weak inhibitors included erythromycin, verapamil, amiodarone, diltiazem, and dronedarone...Conclusions Colchicine was frequently prescribed for acute gout flares in patients with severe chronic kidney disease despite society guideline recommendations, although co-prescription with strong CYP3A4 or P-glycoprotein inhibitors was uncommon. These findings suggest partial adherence to recommendations and warrant further evaluation of colchicine safety in patients with severe chronic kidney disease."

Chronic Kidney Disease • Gout • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatology • CYP3A4

A robust pH-based second-order spectrophotometric method for the analysis of four anti-HIV drugs in pharmaceutical formulations. (PubMed, Sci Rep) - "A robust pH-based second-order spectrophotometric strategy combined with parallel factor analysis (PARAFAC) was developed for the simultaneous determination of elvitegravir (EVG), cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) in pharmaceutical formulations. The proposed strategy successfully preserved the second-order advantage, enabling reliable quantification in the presence of uncalibrated tablet excipients without prior separation. In addition to its satisfactory predictive capability, the method provides a simple, low-cost, and experimentally accessible alternative to chromatographic approaches for multicomponent pharmaceutical analysis."

Journal • Human Immunodeficiency Virus • Infectious Disease

Pulmonary toxicity associated with increased 6-OH-paclitaxel exposure in pancreatic cancer patients treated with nab-paclitaxel, gemcitabine and cobicistat: Results of the IntenSify trial (AACR 2026) - P1 | "Overall, the combination of gemcitabine and nab-paclitaxel with continuous dosing of cobicistat is not safe at the lowest explored dose. We observed pulmonary toxicity with ground glass opacity and LDH increased associated with ~2.5-fold increased 6-OH-paclitaxel levels. Higher metabolite levels were associated with increased severity of findings."

Adverse events • Clinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CYP3A5

Renal and Cardiovascular Complications Following Type 2 Diabetes Mellitus in People With and Without HIV: Data from Cohort Study on Morbidity and HIV in Sweden (COSMOHS) between 2010-2024. (PubMed, Clin Infect Dis) - "In this nationwide cohort, PWH with T2DM exhibited higher risk of renal complications than PWoH, indicating enhanced renal monitoring may be warranted. Further research should investigate underlying mechanisms, including antiretroviral therapy, to guide clinical management."

Journal • Cardiovascular • Diabetes • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Type 2 Diabetes Mellitus

FORTE: A phase 2 master protocol assessing plixorafenib for BRAF-altered cancers (AACR 2025) - P2 | "All patients receive plixorafenib continuous dosing, in some cohorts coadministered with cobicistat, a pharmacokinetic booster. Tumors assessed at cycle 1 day 1, every 9 weeks for 48 weeks, then every 12 weeks. 4Plasma ctDNA assessments for all patients; plasma and CSF assessments for patients with primary CNS tumors.BICR, blinded independent central review; BOP2, Bayesian optimal phase 2; CSF, cerebrospinal fluid; ctDNA, circulating tumor DNA; DCR, disease control rate; DOR, duration of response; HGG, high-grade glioma; LGG, low-grade glioma; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetic; RANO, Response Assessment in Neuro-oncology; RECIST, Response Evaluation Criteria in Solid Tumors."

Clinical • P2 data • Biliary Cancer • Brain Cancer • Cholangiocarcinoma • CNS Tumor • Colorectal Adenocarcinoma • Colorectal Cancer • Cutaneous Melanoma • Endocrine Cancer • Gastrointestinal Cancer • Glioma • Gynecologic Cancers • High Grade Glioma • Lung Cancer • Melanoma • Neuroendocrine Carcinoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Small Intestinal Carcinoma • Solid Tumor • Thyroid Gland Carcinoma • BRAF

Optimizing Tacrolimus Target Trough Levels in Organ Transplantation Among Patients Living With HIV Receiving Antiretroviral Therapy. (PubMed, Clin Transplant) - "Optimizing tacrolimus exposure-rather than HIV status itself-is central to transplant outcomes in PLWH. Integrating ART-informed dosing, formulation flexibility, and advanced TDM strategies may reduce variability, improve graft outcomes, and inform future guideline development for this expanding transplant population."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Solid Organ Transplantation • Transplantation

Synergistic antifungal activity of antiretrovirals with amphotericin B against Aspergillus species. (PubMed, PLoS One) - "From this hit set, we prioritized the two FDA-approved HIV drugs, cobicistat and elvitegravir, as promising lead candidates. These combinations also disrupted mature biofilms, achieving up to 80% eradication, a substantial improvement over AmB alone. These findings highlight the potential of these drug combinations as promising treatment options for aspergillosis, leveraging already approved therapies."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pulmonary Disease • Respiratory Diseases

KF2025#1 Trial: Ketamine, Cannabidiol and Cobicistat Interaction Study (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Helsinki University Central Hospital

New P1 trial

AUGMENT-101: A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation (clinicaltrials.gov) - P1/2 | N=447 | Recruiting | Sponsor: Syndax Pharmaceuticals | N=67 ➔ 447

Enrollment change • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A • NPM1 • NUP98

KF2024#1-trial: Esketamine Interaction Study (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Helsinki University Central Hospital | Not yet recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Apr 2025 | Trial primary completion date: Dec 2025 ➔ Apr 2025

Trial completion • Trial completion date • Trial primary completion date

KF2025#1 trial: Ketamine, cannabidiol and cobicistat interaction study (clinicaltrialsregister.eu) - P1 | N=12 | Not yet recruiting | Sponsor: HUS-yhtymae

New P1 trial

Metabolic dysfunction-associated steatotic liver disease linked to antiretroviral exposure in cohort of people with HIV. (PubMed, AIDS) - "Our findings suggest that commonly used antiretrovirals may contribute to the development of MASLD. Prospective studies examining the possible causal effects of these therapies on MASLD development and progression are warranted."

Journal • Diabetes • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Mapping drug-drug interactions in pharmacokinetic boosting of olaparib. (PubMed, Cancer Chemother Pharmacol) - "DDIs were highly prevalent when PK boosting of olaparib is applied. Nonetheless, nearly all DDIs could be mitigated by an intervention and most interventions could be applied without additional monitoring. PK boosting of olaparib with cobicistat is thus considered feasible with appropriate expertise and resources."

Journal • PK/PD data • Retrospective data • Oncology

Towards human cardiac new approach methodologies (NAMs) to evaluate the combination of repolarization prolonging and shortening drugs: a pilot study. (PubMed, Front Drug Discov (Lausanne)) - "We conclude that cobicistat can attenuate moxifloxacin induced FPDcF prolongation at clinically relevant concentrations in vitro. Taken together, this work provides a foundation to evaluate drug combinations in vitro to aid regulatory decision-making and reduce the dependence on animal studies."

Journal • Cardiovascular