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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

PubMedProtein science : a publication of the Protein Society2026-08-05

Conformational asymmetry of human immunodeficiency virus-1 protease flaps increases along the darunavir drug resistance pathway.

Guerrero Michel M, Zadorozhnyi Roman R, Lin Guowu G, Quinn Caitlin M CM et al.

Under selective drug pressure, the structure and dynamics of HIV-1 protease (PR) evolve to confer resistance to the drug. Here, we report on the conformational changes in PR flaps for drug-resistance mutations using 19F nuclear magnetic resonance (NMR) spectroscopy. We prepared wild-type (wt) PR and its three mutant variants containing 4, 10, or 11 mutations, namely 4Mut, 10Mut, and 11Mut, that were previously found in a viral passage study against darunavir (DRV). The proteins were uniformly labeled with 15N and with 19F amino-acid specifically in the 5-indole positions of two conserved tryptophan residues, W6 and W42, which are located near the dimer interface and at the edge of the flap region of PR, respectively. In solution, 19F NMR spectra of these proteins in the inhibitor-free forms showed a downfield shift of the W42 resonance as the number of mutations increased. In the DRV-bound form, the W42 resonance again shifted with increasing number of mutations and, importantly, split into two peaks, reflecting different local electronic environments of the two flaps of the dimer. Solid-state 19F magic angle spinning (MAS) NMR spectra of wt-PR and 10Mut also exhibited two W42 resonances in DRV-bound crystalline forms. These observations indicate that drug-resistance mutations increase the asymmetry between the two flaps in the PR-inhibitor interaction in the inhibitor-bound forms.

PMID 42554278
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PubMedWorkplace health & safety2026-07-27

Workplace Safety Considerations in Post-Exposure HIV Prophylaxis: A Case Report of Atypical Hypersensitivity in a Healthcare Worker.

Goel Riya R, Aspey Laura Delong LD, Lugo-Diaz Ghiara Alexandra GA, Kaonga Nadi Nina NN et al.

Post-exposure prophylaxis (PEP) with antiretroviral therapy is highly effective in preventing human immunodeficiency virus transmission but can be complicated by hypersensitivity reactions, particularly when sequential regimen substitution is required due to adverse events. We describe the case of a 58-year-old female physician who developed an acute vulvovaginal hypersensitivity reaction within one hour of initiating bictegravir/emtricitabine/tenofovir alafenamide for occupational PEP, followed by drug-induced hypersensitivity syndrome after substitution with darunavir. The patient completed her prophylactic course and did not seroconvert to human immunodeficiency virus or hepatitis B virus. This progression illustrates two novel points: (1) vulvovaginal mucosal hypersensitivity as an underrecognized phenotype of bictegravir/emtricitabine/tenofovir alafenamide toxicity, and (2) heightened risk of severe reactions with sequential prescribing in patients with prior sulfonamide allergy. The case highlights the value of allergy risk stratification in urgent PEP protocols and underscores an opportunity to strengthen sex-specific safety reporting in antiretroviral research. Integrating these considerations into occupational health practice may help prevent life-threatening adverse events, reduce time away from work, and support healthcare worker well-being and productivity.

PMID 42503991
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PubMedCureus2026-07-15

Reversible HIV-Associated Nephropathy and Concomitant Encephalomyelopathy as the Initial Presentation of Advanced, Untreated HIV.

Ya Minn Mya M, Umer Muhammad Qasim MQ, Madu Andrew Chisom AC, Stacey Hannah H et al.

Human immunodeficiency virus (HIV) can cause severe multiorgan dysfunction when left untreated. Concurrent, severe renal and central nervous system manifestations as the primary presentation of advanced HIV are rare in modern clinical practice. We report a case of a young female presenting with dialysis-dependent acute kidney injury (AKI) from HIV-associated nephropathy (HIVAN) and paraplegia from HIV encephalomyelopathy, both of which demonstrated remarkable recovery following antiretroviral therapy (ART). A 31-year-old female presented with a 1-week history of pyrexia, malaise, and rapidly progressive bilateral lower limb weakness. She is a PLHIV (people living with HIV) and was diagnosed seven years ago; she had defaulted from follow-up before starting ART. Laboratory investigations revealed stage 3 AKI, with serum creatinine rising from 403 umol/L on admission to 1112 umol/L within two weeks, alongside high-grade proteinuria. Serology confirmed a plasma HIV-1 RNA viral load of 3,440,753 copies/mL and a CD4 T-cell count below the limit of detection (<8 cells/uL). A renal biopsy demonstrated classic histopathological features of HIVAN, showing collapsing glomerulopathy. Magnetic resonance imaging (MRI) of the brain and spine demonstrated extensive, diffuse abnormal T2-weighted fluid-attenuated inversion recovery (T2/FLAIR) signal intensities involving the cerebral hemispheres, basal ganglia, brainstem, and a long segment of the cervical cord, consistent with an advanced neuro-axis injury. Cerebrospinal fluid (CSF) analysis and CSF culture ruled out opportunistic neuro-infections. The patient was initiated on regular haemodialysis and an intensive antiretroviral regimen consisting of dolutegravir/lamivudine, darunavir, and ritonavir, alongside co-trimoxazole prophylaxis until her CD4 count was over 200 cells/mm3. Over a five-month follow-up period, the patient demonstrated an impressive clinical response. Her plasma viral load decreased to 41 copies/mL, serial neuroimaging revealed substantial resolution of the extensive intracranial and spinal cord lesions, together with recovery of motor power to 5/5 in all 4 limbs, and recovery of renal function, which allowed for the successful cessation of long-term haemodialysis. This case underscores that advanced HIVAN requiring renal replacement therapy and extensive HIV-related central nervous system pathology can be profoundly reversed with timely, potent antiretroviral therapy. Clinicians must maintain a high index of suspicion for HIV in patients presenting with unexplained concurrent multiorgan dysfunction, as early intervention can avert permanent end-stage organ failure and severe neurological disability.

PMID 42454235
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PubMedInternational journal of antimicrobial agents2026-07-14

Outcomes for persons with triple-class resistant HIV and a history of virologic failure.

Ingle Suzanne M SM, Bonnet Fabrice F, Wittkop Linda L, Calmy Alexandra A et al.

To assess outcomes of heavily treatment experienced people with HIV (PWH) who received the antiretroviral therapy salvage regimen containing raltegravir, etravirine, and darunavir/ritonavir (known as TRIO). Data were from the ART Cohort Collaboration, which is a collaboration of European and North American HIV cohort studies. Adult PWH were eligible if they had a history of virologic failure while receiving nonnucleoside reverse-transcriptase inhibitors; three or more primary protease inhibitor and nucleoside reverse transcriptase inhibitor mutations; three or fewer darunavir and nonnucleoside reverse-transcriptase inhibitor mutations; received TRIO between 2007 and 2018; virologic failure at TRIO start; and did not receive any TRIO drugs previously. Follow-up began at TRIO start. We examined rates of virologic suppression on TRIO, AIDS/death, receipt of drug-reducing regimens post-TRIO in those virologically suppressed, and subsequent virologic response. We used a competing risks framework to estimate 5-y cumulative incidence of outcomes. Among 126 eligible PWH, 24% were female, and median age was 46 y (IQR: 41-50). Median follow-up was 7.9 y (IQR: 5.1-9.3). A total of 94 (74.6%) were virologically suppressed on TRIO. Of these, 26 (28%) subsequently switched to a drug-reducing regimen, of whom 19 of 26 (73.1%) were virologically suppressed at their next viral load measure. The 5-y cumulative incidence of outcomes was stop TRIO and start another three or more drug regimen (39.1%); simplify (16.0%); stop TRIO without switching (8.8%); and death on TRIO (7.2%). Although the most common outcome after TRIO was switch to another three or more drug regimen, almost one third of virologically suppressed PWH under TRIO (with a history of multidrug resistance) switched to a drug-reducing regimen, the majority of whom maintained suppression.

PMID 42442619
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PubMedJournal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi2026-07-11

Is the HIV-2 pandemic going extinct 40 years after virus discovery?

Soriano Vicente V, Konan Berenger B, Segla Rose R, Moreno-Torres Víctor V et al.

A close but genetically divergent retrovirus named HIV-2 was discovered in 1986 in West African patients with AIDS negative or indeterminate for HIV-1 antibodies. Viral replication is lower in HIV-2, being plasma viremia often undetectable or low. As result, HIV-2 transmission either by sex or vertically, is lower compared to HIV-1. Alongside, CD4+ T-cell declines occur slowly and clinical manifestations of immunodeficiency may appear after 15 years in HIV-2 patients. Over 10% of HIV-2 carriers may remain asymptomatic lifelong. The susceptibility of HIV-2 to antiretroviral drugs is generally lower than for HIV-1, being non-nucleoside reverse transcriptase inhibitors non active. Some protease inhibitors, as darunavir, are effective. All integrase inhibitors block HIV-2, and either dolutegravir or bictegravir are the preferred drug choices. Specific viral load tests must be used to monitor HIV-2 plasma viremia. Trends in epidemiological surveys confirm that the HIV-2 pandemic is falling down with less infected persons yearly in endemic regions and globally.

PMID 42431766
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PubMedVirology journal2026-07-11

Major protease inhibitor drug resistance mutations among patients with virological failure on second-line antiretroviral therapy in Zimbabwe: a retrospective cross-sectional study.

Mayini Justin J, Washaya Tendai T, Manasa Justen J, Zumbika Edward E et al.

Virological failure (VF) on protease inhibitor (PI)-based second-line antiretroviral therapy (ART) remains an important driver of HIV drug resistance (HIVDR) in sub-Saharan Africa. Despite widespread adoption of dolutegravir (DTG)-based first-line ART, many people living with HIV (PLWH) remain on PI-based second-line regimens. Data on major PI drug resistance mutations (DRMs) in Zimbabwe remain limited. We conducted a retrospective cross-sectional study of archived plasma specimens from PLWH with VF (viral load (VL) ≥ 1,000 copies/mL) receiving PI-based second-line ART in Zimbabwe between January 2021 and June 2025. HIV-1 protease and reverse transcriptase regions were Sanger-sequenced, and resistance was interpreted using the Stanford HIV Drug Resistance Database. Factors associated with major PI DRMs were evaluated using multivariable logistic regression. Among 297 participants, 153 (51.5%, 95% confidence interval [CI] 45.8-57.2%) harboured major PI DRMs. The most frequent mutations were M46I (22.6%), V82A (19.2%), and I54V (17.2%). NRTI- and NNRTI-associated DRMs were present in 70.4% and 79.5% of participants, respectively, while 47.8% exhibited triple-class resistance. Predicted susceptibility to darunavir/ritonavir remained high (78.8%), despite resistance to atazanavir/ritonavir (45.5%) and lopinavir/ritonavir (50.8%). In multivariable analysis, increasing age (adjusted odds ratio [aOR] 1.04, P < 0.001), higher VL (aOR 1.55, P = 0.011) and male sex (aOR 1.59, P = 0.044) were independently associated with major PI DRMs. Major PI DRMs and multiclass HIVDR were common among PLWH with VF on PI-based second-line ART. Routine VL monitoring and early resistance testing are needed to detect and guide second-line ART failure in Zimbabwe.

PMID 42432698
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