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cobicistat + darunavir (G006 / Rezolsta / Prezcobix)

✓ Approved

Johnson & Johnson Services, Inc. · CYP3A4 · 小分子

什么是 cobicistat + darunavir？

cobicistat + darunavir 是一种小分子，由Johnson & Johnson Services, Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名G006, Rezolsta, Prezcobix
公司Johnson & Johnson Services, Inc.
药物类别小分子
分子靶点CYP3A4,
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Johnson & Johnson Services, Inc.

作用机制

分子靶点

cobicistat + darunavir 作用于 2 个分子靶点：

CYP3A4cytochrome P450 family 3 subfamily A member 4 (CP33, HLP)
gag-pol, HIV-1 (gag-pol)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

cobicistat + darunavir 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Infections and infestationsAcquired immunodeficiency syndrome✓ Approved

相关研究文献

PubMedJournal of pharmacy practice2026-10-26

Dose-Reduced Apixaban for Thromboembolism in a Patient With Obesity on Cobicistat: A Case Report.

Womble Katlyn K, Mize Marcus M, Baker Carrie C, Bowers Riley R

Background/Objective: Current guidelines recommend a 50% dose reduction of apixaban for patients receiving strong CYP3A4/P-glycoprotein (P-gp) inhibitors regardless of body habitus. However, evidence supporting this dose adjustment in patients with severe obesity (BMI >40 kg/m2) is limited. This report describes the use of dose-reduced apixaban for the treatment of venous thromboembolism in a patient with a BMI >50 kg/m2 receiving a strong CYP3A4/P-gp inhibitor. Summary: A 38-year-old female with a BMI of 81.71 kg/m2 and a history of HIV on a cobicistat-containing antiretroviral regimen was diagnosed with a left femoral deep vein thromboembolism. She was initially treated with warfarin and enoxaparin bridge therapy but was transitioned to apixaban prior to discharge. Apixaban was initiated at a 50% dose reduction due to the concomitant use of cobicistat, a strong CYP3A4/P-gp inhibitor. The patient successfully completed therapy without recurrence of thromboembolism or bleeding complications. Conclusion: This case demonstrates the successful use of dose-reduced apixaban in a patient with a BMI >50 kg/m2 receiving a CYP3A4/P-gp inhibitor for the treatment of venous thromboembolism and adds to available literature on apixaban dosing in patients with obesity.

PMID 42933124
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PubMedAntiviral research2026-10-26

WG-am combinations restore antiviral potency against fostemsavir and lenacapavir-resistant HIV-1.

Giammarino Federica F, van de Klundert Maarten Aa MA, Saladini Francesco F, Zazzi Maurizio M et al.

Resistance to fostemsavir (FTR) and lenacapavir (LEN) poses critical challenges for heavily treatment-experienced (HTE) people with HIV-1 who have exhausted conventional therapeutic options. We evaluated the antiviral synergy of tryptophylglycine-amide (WG-am), a naturally occurring dipeptide from HIV-1 elite controllers that inhibits viral entry and reverse transcription, in combination with seven antiretrovirals against FTR- and LEN-resistant HIV-1 viruses. Combination assays were performed in TZM-bl cells using a 7×7 dose-matrix format against nine HIV-1 viruses with defined FTR- or LEN-resistance mutations. Synergy was quantified using the zero-interaction potency (ZIP) model in SynergyFinder across all concentrations and at the ≥90% viral inhibition threshold. Three priority combinations - with ibalizumab (IBA), darunavir (DRV), and FTR - were validated in activated PBMCs from three independent donors. WG-am demonstrated synergistic or additive interactions with all seven antiretrovirals; no antagonism was detected. IBA and DRV showed the highest and most consistent synergy across both resistance backgrounds. FTR showed paradoxical synergy against FTR-resistant virus (peak ZIP 15.58 against S375T). At the ≥90% inhibition threshold, 87.3% (55/63) of combination pairs were synergistic. PBMC validation confirmed synergy for all six priority combinations (ZIP 11.01-17.19), with WG-am + FTR scores exceeding TZM-bl values in primary cells. WG-am-based combinations demonstrate synergistic antiviral activity against FTR- and LEN-resistant HIV-1 in reporter cells and primary immune cells. IBA, DRV, and FTR are identified as priority combination partners for WG-am as a component of resistance-informed salvage regimens for HTE patients with limited treatment options.

PMID 42933201
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PubMedJournal of chemical theory and computation2026-10-23

Coupling Quantum Mechanical Modeling and Molecular Dynamics on Heterogeneous Supercomputers for Studying Distal Mutation Effects on Drug Binding in HIV-1.

Dawson William W, Beal Louis L, Zaccaria Marco M, Genovese Luigi L

Predicting how protein mutations affect drug binding remains a major challenge, particularly when the mutations are distal from the binding site. In this study, we introduce a coupled simulation workflow that combines classical molecular dynamics (MD) with high-throughput quantum mechanical (QM) analysis to reveal the electronic structure signatures of mutation-induced drug resistance in the HIV-1 protease. Our workflow leverages GPU-accelerated MD to generate conformational ensembles, and performs in operando linear-scaling density functional theory (DFT) calculations on selected frames parallelized on a coupled partition of CPU nodes. This design enables efficient, massively parallel quantum analysis of protein-ligand complexes at atomic resolution. Using this approach, we investigate resistance to the antiviral Darunavir in a multimutant HIV-1 protease variant. By mapping the network of electronic interactions across the binding interface, our results highlight the critical role of conformational sampling and quantum insight in understanding distal mutation effects, and demonstrate a scalable computational strategy for studying complex biophysical mechanisms of drug resistance. We argue that this type of analysis may pave the way for designing inhibitors that maintain binding stability against systemic, mutation-induced destabilization.

PMID 42917266
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PubMedbioRxiv : the preprint server for biology2026-10-11

A Dynamics-Informed Machine Learning Framework for Inhibitor Optimization Against Quickly Evolving Targets to Avoid Resistance.

Intravaia Lauren E LE, Kaur Jagroop J, Shaqra Ala M AM, Henes Mina M et al.

Drug resistance often emerges through mutations that reshape protein conformational ensembles, allowing inhibitor potency to be altered without directly disrupting protein-ligand contacts. Consequently, the molecular mechanisms underlying these effects remain difficult to identify, hindering the design of inhibitors with durable potency against rapidly evolving drug targets. To address this challenge, we developed ROBUST, a physics-informed machine learning framework that integrates experimental measurements, molecular dynamics simulations, and interpretable statistical modeling to identify energetic determinants of inhibitor potency. Using HIV-1 protease as a stringent model system for drug resistance, we determined 157 new inhibition constants and integrated them with prior measurements to establish a comprehensive experimental dataset of 364 protease-inhibitor pairs. Analysis of the corresponding molecular dynamics simulations revealed a compact network of energetic interactions that quantitatively explains how resistance mutations and inhibitor modifications jointly reshape molecular recognition and inhibitor potency across the multidimensional resistance landscape. Models constructed from these energetic signatures predicted binding free energies with high accuracy (RMSE < 1 kcal mol-1) and successfully generalized to unseen darunavir analogs. Importantly, ROBUST accurately prioritized unseen analogs based on their potency across the variant set, demonstrating its utility for identifying compounds with improved resistance profiles. Together, these results uncover the energetic principles through which resistance mutations and inhibitor modifications alter potency and establish ROBUST as a mechanistically interpretable framework for translating these insights into resistance-aware inhibitor optimization against rapidly evolving drug targets.

PMID 42856246
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PubMedBritish journal of clinical pharmacology2026-10-06

Lenacapavir initiation with concomitant primidone: A case report with therapeutic drug monitoring.

Devanathan Aaron S AS, Glowa Thomas T, Thompson Emily M EM, Saylor Amanda J AJ et al.

Lenacapavir (LEN), a first-in-class capsid inhibitor, has unique pharmacokinetics that enable twice-yearly dosing. LEN is not extensively metabolized, although it is a substrate of CYP3A4, which introduces drug-drug interactions concerns. As adoption and implementation of LEN for treatment and prevention increase, additional guidance on concomitant medications with LEN is needed. Primidone is a barbiturate type anticonvulsant medication and a moderate-to-strong inducer of CYP3A4. A primary metabolite of primidone, phenobarbital, also induces CYP3A. Consequently, the coadministration of LEN and primidone is not recommended due to the potential induction of CYP3A-mediated metabolism and resultant subtherapeutic LEN concentrations. However, the extent to which LEN concentrations may decrease alongside concomitant primidone is unknown. Herein, we describe a 67-year-old male initiating LEN following switch from a boosted darunavir regimen, alongside long-standing treatment with primidone 50 mg daily. Blood samples were collected throughout the first 6-month dosing interval. Plasma LEN concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry analytical method. LEN concentrations remained above four times the protein adjusted 95% effective concentration during the measured time points. The lowest observed concentration was 24.9 ng/mL at Month 1; the highest observed was 58.3 ng/mL at Month 3. The projected 6-month concentration was 40.6 ng/mL. Observed concentrations were generally consistent with concentrations reported in prior studies in the absence of clinically-significant drug-drug interactions. Viral load measures remained undetectable throughout the dosing interval and following subsequent administrations thereafter. This case provides pharmacokinetic rationale for the coadministration of LEN with primidone and may help guide future clinical decision-making.

PMID 42836661
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PubMedThe Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases2026-09-27

Persistent low-level viremia and symptomatic HIV cerebrospinal fluid escape in a person living with HIV receiving darunavir: a case report.

Suriano Enrico Stefano ES, Kuslevicius Karin K, Leal Mariana Martins Dos Santos MMDS, Relvas Luiz Fernando Degrecci LFD et al.

HIV Cerebrospinal Fluid (CSF) viral escape is a condition characterized by inadequate virological control within the CSF despite systemic antiretroviral therapy, often assessed through discordant CSF and plasma HIV viral loads. The clinical relevance of CSF viral escape remains poorly understood, but it is thought to contribute to a spectrum of neurological and neurocognitive manifestations. The present study details the case of a 51-year-old individual from São Paulo, Brazil, presenting with acute meningoencephalitis and seizures in the context of persistent low-level viremia. Differential diagnoses were considered to rule out other conditions, such as infectious and immune-related diseases, eventually leading to a diagnosis of HIV CSF viral escape, confirmed through clinical presentation and a series of diagnostic evaluations. Antiretroviral therapy was subsequently optimized to improve central nervous system penetration, resulting in clinical improvement, resolution of neurological symptoms and undetectable CSF viral load.

PMID 42800342
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