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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

PubMedInternational journal of microbiology2026-09-08

Comparative and Subtractive Genomics Analysis of Multidrug-Resistant Klebsiella pneumoniae Strains for Novel Target Identification and Drug Repurposing Strategies.

Bora Manasi M, Paul Prokriti P, Rajkhowa Sanchaita S, Sonar Harshita H et al.

The rapid rise of multidrug-resistant (MDR) Klebsiella pneumoniae has created a major global health challenge due to the limited availability of conserved therapeutic targets effective across diverse resistant strains. In this study, an integrative computational target-discovery and drug-repurposing framework was applied to six clinically relevant K. pneumoniae strains. Comparative genomic analysis identified 3012 conserved genes, which were subsequently filtered to nine essential, non-host homologous proteins. Among these, three conserved cytoplasmic proteins (accD, cpxR, and mraZ) were prioritized for functional analysis, with acetyl-CoA carboxylase subunit beta (accD) emerging as the most promising therapeutic target based on sequence conservation, predicted essentiality, subcellular localization, and pathway association. Structural assessment supported the reliability of the predicted accD model, whereas consensus binding-site analysis identified key residues suitable for ligand interaction. Virtual screening of FDA-approved drugs followed by molecular docking identified several compounds with favorable binding profiles toward accD. 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.

PMID 42707355
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PubMedIDCases2026-09-06

Multiclass HIV drug resistance: Case series of treatment-experienced PLHIV with resistance to all antiretroviral classes in Northern Uganda.

Kayinda Francis F, Bakunzi Lillian Betty LB, Okello Edmund E, Jurua Charity C et al.

Multiclass HIV drug resistance (HIVDR) is an emerging public health challenge in Uganda, especially among treatment-experienced individuals with long antiretroviral therapy (ART) histories. Resistance across nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) limits treatment options and threatens program sustainability. This study describes three cases of multiclass HIVDR in West-Nile region of Uganda. A descriptive case series was conducted among people living with HIV (PLHIV) with documented virological failure and confirmed resistance to all four ART classes between January 2023 and December 2024. HIVDR testing used next-generation sequencing, and resistance mutations were interpreted with Stanford HIVDR database. Clinical data were abstracted and analyzed descriptively. Three cases were identified: two females (20 and 42 years) and one male (14 years), after approximately 10 years on ART. Shared factors included delayed viral load (VL) monitoring, prolonged exposure to failing regimens, delayed resistance testing and adherence challenges related to stigma and psychosocial barriers. All had been exposed to dolutegravir (DTG)-based regimens and developed intermediate-to-high level resistance to DTG alongside mutations in the other classes. Two cases achieved viral suppression < 1000 copies/ml on salvage therapy. These cases demonstrate that high-barrier drugs like DTG and Darunavir remain vulnerable when virological failure persists and adherence is suboptimal. Strengthening VL monitoring, access to genotypic testing and adherence support is essential to prevent Multiclass HIVDR.

PMID 42699134
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PubMedJournal of acquired immune deficiency syndromes (1999)2026-09-04

Pharmacokinetics/Pharmacodynamics, Safety, and Tolerability of Rivaroxaban with Cobicistat or Darunavir/Cobicistat in Healthy Participants.

Adeojo Lilian W LW, Pauls Cheryl C, Swaim Doris D, Kumar Parag P et al.

Direct oral anticoagulants such as rivaroxaban are a feasible and convenient option for anticoagulation in people living with HIV. Here, we assess the effect of cobicistat or darunavir/cobicistat on the pharmacokinetics (PK), pharmacodynamics (PD), and safety of rivaroxaban. This open-label, fixed sequence, intrasubject drug-drug interaction PK study enrolled healthy participants who received oral study drugs sequentially as follows: rivaroxaban 10 mg once on day 1, cobicistat 150 mg once-daily on days 2 to 7, rivaroxaban 10 mg once on day 7, darunavir/cobicistat 800/150 mg once-daily on days 8 to 13 followed by rivaroxaban 10 mg once on day 13. Serial PK and PD plasma samples were obtained on days 1, 7, and 13 over 24 hours. Safety was assessed throughout the study. Twelve participants enrolled and completed three phases of the study. Rivaroxaban geometric mean ratios (GMR, rivaroxaban + cobicistat versus rivaroxaban alone) and 90% confidence interval (CI) for Cmax and AUC0-∞ were 1.50 (1.10-1.90) and 2.14 (1.70-2.58), respectively. Rivaroxaban GMR (rivaroxaban + darunavir/cobicistat versus rivaroxaban alone) and 90% CI for Cmax and AUC0-∞ were 1.53 (1.13-1.94) and 2.12 (1.68-2.56), respectively. Rivaroxaban concentrations were positively correlated with PD markers in a linear fashion and returned to near-baseline 24 hours post-dose. All adverse events were mild to moderate in severity and resolved by the end of the study. Coadministration of cobicistat and cobicistat-boosted darunavir with rivaroxaban resulted in a clinically significant increase in rivaroxaban drug exposure. Further study can inform safety and efficacy of rivaroxaban dose reduction.

PMID 42696729
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PubMedThe Journal of antimicrobial chemotherapy2026-09-04

Switching from etravirine to doravirine in people with HIV harbouring NNRTI resistance-associated mutations: the DorSwitch pilot study.

Sempere Abiu A, de la Mora Lorena L, Inciarte Alexy A, Berrocal Leire L et al.

The objective of this study is to evaluate the efficacy, resistance profile, pharmacokinetics (PK) and safety of switching from etravirine to doravirine in virologically suppressed, treatment-experienced individuals with prior non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated resistance mutations (NNRTI-RAMs). DorSwitch is a prospective pilot study including 13 adults with sustained virological suppression and documented historical NNRTI-RAMs. Etravirine was replaced by doravirine while maintaining the remaining antiretroviral backbone. Drug-specific resistance penalty scores were generated using the Stanford HIV Drug Resistance Database (HIVdb) algorithm. PK analyses were performed in participants receiving darunavir/cobicistat plus doravirine. Virological, immunological, metabolic and safety outcomes were assessed over 48 weeks. Twelve participants completed 48 weeks of follow-up; one discontinued at Week 4 for personal reasons while virologically suppressed. All participants evaluable at Weeks 24 and 48 maintained HIV-1 RNA < 50 copies/mL, and no virological failures occurred. The median number of NNRTI-RAMs per individual was 2 (IQR 1-3). Doravirine showed lower or equal Stanford HIVdb penalty score (HIVdb-PS) than etravirine in 11/13 participants. In two cases, higher doravirine PS were driven by Y318F and G190E mutations detected in peripheral blood mononuclear cell HIV-1 DNA; both individuals remained virologically suppressed through Week 48. In seven participants receiving darunavir/cobicistat plus doravirine, trough concentrations (Cmin) were consistent with expected exposure concentrations. Total cholesterol and LDL cholesterol decreased significantly over follow-up, while body weight showed a modest, non-significant reduction. No doravirine-related serious adverse events were observed. In this small, highly selected pilot cohort, switching from etravirine to doravirine as part of an otherwise suppressive regimen was associated with maintenance of virological suppression through Week 48 and a more favourable predicted NNRTI resistance profile in most participants. The favourable resistance profile, safety, metabolic effects and PK findings consistent with expected exposure-particularly in combination with darunavir/cobicistat- support further evaluation of doravirine as a switch option in carefully selected individuals with prior NNRTI failure.

PMID 42695345
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PubMedMicroorganisms2026-08-27

Longitudinal Clinical and Molecular Characterization of a Single Pediatric Case of Vertically Acquired HIV-1 Subtype C with Baseline Resistance to Protease Inhibitors.

Zaher Kawther A KA, El-Daly Mai M MM, Zaki Eitezaz A EA, Alhazmi Mohammad M MM et al.

Transmitted HIV drug resistance can compromise treatment outcomes in children with vertically acquired infection, particularly when baseline resistance testing is unavailable. This case report describes the longitudinal clinical, virological, immunological, and molecular course of a male child diagnosed with vertically acquired HIV-1 subtype C infection, most consistent with mother-to-child transmission. Clinical history, viral load, CD4/CD8 profiles, HIV-1 pol sequencing, phylogenetic analysis, and interpretation were performed using the Stanford HIV Drug Resistance Database (HIVdb). The baseline viral load was 240,993 copies/mL, with a CD4:CD8 ratio of 0.40. Genotypic analysis identified major protease inhibitor resistance mutations V82A and I84I/V, together with M184V. Stanford HIVdb predicted high-level resistance to lopinavir/ritonavir, atazanavir/ritonavir, lamivudine, and emtricitabine; low-level resistance to darunavir/ritonavir and abacavir; and preserved susceptibility to tenofovir, zidovudine, and the evaluated NNRTIs. Initial lopinavir/ritonavir-based regimens failed to achieve sustained virological suppression. Following treatment optimization with an integrase inhibitor-based regimen and subsequent transition to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), HIV-1 RNA became Target Not Detected (TND) from November 2024 onward. At the latest follow-up, the CD4 count was 877 cells/µL, the CD8 count was 722 cells/µL, and the CD4:CD8 ratio had improved to 1.21, indicating substantial immune recovery. This single-patient case highlights the clinical value of baseline genotypic resistance testing and individualized, genotype-guided antiretroviral therapy in achieving durable virological suppression in pediatric HIV.

PMID 42654980
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PubMedJournal of xenobiotics2026-08-26

Activated Sludge in the Bioremediation of Water Containing SARS-CoV-2 Antivirals.

Lastovčić Dora D, Zirn Ivona I, Jezerčić Tijana T, Bule Možar Kristina K et al.

The increasing presence of SARS-CoV-2 antivirals (SASs) in wastewater threatens aquatic ecosystems, making it necessary to better understand their removal efficiency during biological treatment. This study evaluates the removal percentages, kinetic mechanisms, and toxicity profiles of six SASs, daclatasvir (DCV), darunavir (DRV), favipiravir (FAV), lopinavir (LOP), remdesivir (REM), and ritonavir (RIT), using activated sludge. A full factorial design combined with response surface methodology (RSM) was used to assess the impact of pH, temperature (T), and mixed liquor suspended solids (MLSS) on SAS removal and microbial stability. The results distinguished two dominant removal pathways. DCV and LOP were primarily removed by adsorption, whereas DRV, FAV, REM and RIT were predominantly removed through biodegradation involving enzymatic transformation and bacterial co-metabolism. RSM achieved a desirability score of 0.772 and identified the optimal operating conditions (pH = 6.08, MLSS = 4.41 g/L, and T = 44.99 °C), resulting in removal efficiencies above 93% for all compounds except DRV, which remained the limiting compound with a maximum removal efficiency of 66%. Perturbation analysis showed that all tested factors have a distinct influence on process performance. These established kinetic trends should support further investigations into advanced biological wastewater treatment methods and precise ecotoxicity profiling of emerging biotransformation products.

PMID 42646048
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