Prezista (darunavir) / J&J - LARVOL DELTA

Evaluation of antiretroviral regimen switching options in adults with HIV with sustained viral load non-suppression on dolutegravir, lamivudine, and tenofovir in eastern, central, southern, and western Africa: a modelling study. (PubMed, Lancet HIV) - "Introduction of HIV drug resistance testing for people with sustained viral load non-suppression on dolutegravir-based antiretroviral therapy is likely to be cost-effective. We suggest that exploratory planning for increased access and scale-up of high-quality, low-cost drug resistance testing for the region is undertaken."

Journal • Human Immunodeficiency Virus • Infectious Disease

A randomised trial to compare dolutegravir plus boosted darunavir versus recommended standard of care antiretroviral regimens in people with HIV-1, whose first-line non-nucleoside reverse transcriptase inhibitor therapy has failed: Final 96-week results of the D2EFT study. (PubMed, Clin Infect Dis) - "After 96 weeks of follow-up, DTG+DRV/r and DTG+TDF/XTC demonstrated virological superiority over DRV/r+2NRTIs after first-line NNRTI-failure. However, emerging dolutegravir resistance, which was observed only in individuals taking DTG+TDF/XTC, requires ongoing global surveillance."

Journal • Human Immunodeficiency Virus • Infectious Disease

Bictegravir decreases expression of system L-amino acid transporters and inhibits leucine uptake activity in a human placental cell line. (PubMed, Biomed Pharmacother) - "Syncytialized BeWo cells were treated with atazanavir, darunavir, efavirenz, dolutegravir, raltegravir, bictegravir or cabotegravir for 24 h at Cmax and half Cmax therapeutic concentrations. Bictegravir, which has been recently added to perinatal treatment guidelines, was associated with downregulation of system L expression and function in BeWo cells. Further in vivo studies are warranted to confirm our findings."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

Integrative machine learning and structure-based drug repurposing for identifying potent inhibitors of human SYK activity against cancer. (PubMed, Life Sci) - "Despite the investigation of inhibitors of SYK including fostamatinib, entospletinib, cerdulatinib, and TAK-659 for cancer therapy, their lack of specificity and potential off-target effects remain significant concerns...Rifabutin, darunavir, and sildenafil were found as promising SYK inhibitors, showing strong interactions and stable conformations...Our findings underscore the value of computational methods in drug discovery and advocate for further experimental validation of these compounds as SYK-targeted therapies. This study aims to advance the development of more effective and safer treatments for cancers associated with SYK overexpression."

Journal • Oncology • SYK

Advancing Darunavir Delivery: Nanoformulation strategies and innovations in HIV therapy. (PubMed, Pharm Dev Technol) - "Further, this review discusses challenges associated with nanoformulation-based antiretroviral strategies, scalability, manufacturing challenges, potential toxicity, immunogenicity, long-term stability issues, and explores emerging innovations, such as multifunctional nanoparticles, targeted delivery platforms, and sustainable nanotechnology-based formulations. By systematically evaluating current advances, this analysis provides critical insights into overcoming bioavailability constraints and facilitating the clinical translation of nanocarrier-based antiretroviral therapies."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease

HIV-associated nephropathy in a patient with undetectable viral load: a case report (ERA 2025) - "He was on a regimen of Bictegravir/Emtricitabine/Tenofovir Alafenamide and had additional comorbidities, including chronic lung disease and active smoking...He was diagnosed with influenza A pneumonia and was hospitalized due to hypoxemia, initiating oseltamivir treatment...Two days after admission, the patient developed bacterial pneumonia, and Piperacillin-tazobactam was initiated...ART was subsequently changed to Ritonavir/Darunavir and Dolutegravir... Nephropathy in HIV patients presents a multifactorial challenge. This case highlights the complexity of diagnosing HIVAN, emphasizing the importance of maintaining a high index of suspicion even in patients with undetectable or low HIV RNA levels, particularly in the presence of a history of nonadherence to ART and CD4+ T-cell counts below 200 cells/µL. We may hypothesize if the respiratory infection was the trigger for developing the disease, although the patient had prior de novo proteinuria."

Case report • Clinical • Chronic Kidney Disease • Fibrosis • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Influenza • Metabolic Disorders • Monoclonal Gammopathy • Nephrology • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Renal Disease • Respiratory Diseases • CD4

Early Virologic Success on Antiretroviral Therapy Among Individuals With Breakthrough HIV Acquisition on Long-Acting Cabotegravir Pre-exposure Prophylaxis. (PubMed, Open Forum Infect Dis) - "All started darunavir-based ART; 1 subsequently switched to bictegravir-based ART. All maintained plasma HIV-1 RNA <50 copies/mL through ≥5 months post-ART initiation, providing early evidence of virologic success with standard ART regimens and paving the way for longer-term studies on optimal ART after CAB-LA breakthrough."

Journal • Human Immunodeficiency Virus • Infectious Disease

Tetrahydrofuran-containing Pharmaceuticals: Targets, Pharmacological Activities, and Their SAR Studies. (PubMed, ChemMedChem) - "The US Food and Drug Administration (FDA) has approved a total of 13 drugs for a range of clinical diseases， such as Terazosin and Darunavir. These drugs exhibit superior pharmacological effects in multiple therapeutic fields. This review offers an extensive overview of FDA-approved drugs containing the tetrahydrofuran nucleus, emphasizing their pharmacological activities and structure-activity relationships."

Journal

Rational Design and Multi-tiered Computational Evaluation of Novel Darunavir Derivatives as HIV-1 Protease Inhibitors: an Integrated Approach Using QSAR Model, Molecular Docking, MD Simulations, DFT Analysis, and ADME Profiling. (PubMed, Chem Biodivers) - "Moreover, ADMET was used to verify its pharmacokinetic characteristics, molecular docking was used to verify its binding ability, and kinetic simulation and binding free energy were used to verify the accuracy of the docking results. The comprehensive computational investigation results show that these newly designed molecules have excellent properties and provide potential molecular structure information for the development of novel, highly efficient, and low-toxicity HIV-1 protease-targeting inhibitors."

Journal • Human Immunodeficiency Virus • Infectious Disease

DARUNAVIR-INDUCED PEPSIN INHIBITION IN A GERD MODEL: HIF-2α DRIVEN INFLAMMATION REDUCTION AND TIGHT JUNCTION PROTEINS ENHANCING MUCOSAL INTEGRITY. (DDW 2025) - No abstract available

Gastroesophageal Reflux Disease • Inflammation • EPAS1

Assessment of the steady-state drug-drug interactions between dolutegravir and ritonavir-boosted darunavir in adolescents. (PubMed, AIDS) - "Administration of DRV/r 800/100 mg and DTG 50 mg once daily provides adequate concentrations and exposures with no clinically relevant drug-drug interactions at steady-state."

Journal

Viral suppression after failure of PI-based ART among adolescents and youths with and without drug resistance mutations: a longitudinal analysis in Tanzania. (PubMed, J Antimicrob Chemother) - "More than half of AY who had PI DRMs had a higher proportion of early VS (65%) compared with those without DRMs (45%). Optimal viral load monitoring, adherence intensification and routine drug resistance testing are key strategies to improve VS."

Journal • Human Immunodeficiency Virus • Infectious Disease

Darunavir: A Versatile Protease Inhibitor against Microbial Infections. (PubMed, Curr Drug Discov Technol) - "The present review explores the molecular principles behind the effectiveness of DRV against microbial infections, emphasizing the drug's ability to fight a wide range of pathogens. The comprehension of the intracellular activity of DRV is promising for the creation of novel treatment approaches, providing encouragement in the continuous fight against microbial diseases."

Journal • Human Immunodeficiency Virus • Infectious Disease

Extracellular Vesicle-Liposome-Darunavir Formulation for the Treatment of HIV Neuropathogenesis. (PubMed, ACS Appl Nano Mater) - "Furthermore, analysis of brain tissues from these mice showed significantly reduced HIV-associated inflammatory response, oxidative stress, DNA damage, and neuronal damage in EV-Lip-DRV as compared with DRV alone. Taken together, these findings suggest that EV-Lip is a promising vehicle for enhancing the delivery of antiretroviral drugs to the brain, potentially ameliorating symptoms associated with HIV neuropathogenesis and improving overall outcomes in HIV treatment."

Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease • Inflammation

Virological Failure And HIV-1 Drug Resistance in Indian Adults and Adolescents on Protease Inhibitor Based Second-line Antiretroviral Therapy: A Five-year Follow-up Study. (PubMed, Curr HIV Res) - "This 5-year longitudinal study highlights the resilience of PIs in second-line ART. The incidence of VF with PI-resistance was notably low, indicating the ongoing effectiveness of PIs in managing PLH on second-line ART and the possibility of recycling PIs in subsequent ART regimens for these patients. Cross-resistance to DRV patients highlights the need for enhanced treatment monitoring."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Comparative Analysis of Neuropsychiatric Adverse Reactions Associated with Remdesivir and Nirmatrelvir/Ritonavir in COVID-19 Treatment: Insights from EudraVigilance Data. (PubMed, J Clin Med) - "Comparisons with other antiviral drugs, including darunavir, sofosbuvir, ribavirin, tenofovir, ritonavir, and sotrovimab, are also performed to develop a comprehensive understanding of the safety profiles. NMVr presents a higher risk of neuropsychiatric ADRs than RDV, underscoring the need for enhanced monitoring, particularly in patients with preexisting central nervous system (CNS) conditions. These findings contribute to optimizing antiviral safety and informing clinical decision making."

Journal • CNS Disorders • Infectious Disease • Mental Retardation • Mood Disorders • Movement Disorders • Novel Coronavirus Disease • Pain • Psychiatry • Sleep Disorder

Effectiveness of dolutegravir-based vs boosted darunavir-based first-line 3-drug regimens in people with HIV with advanced disease: a trial emulation. (PubMed, Int J Infect Dis) - "Under the stated assumptions, this analysis indicates that in ART-naïve PWH with advanced disease, ART initiation with DTG vs. DRV/b-based regimens leads to a 50% reduction in the risk of AIDS/SNAE/death/VF/discontinuation. This observed difference is partly explained by discontinuation of the anchor drug."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Week 24 Outcomes of F/TAF Plus Cobicistat-Boosted Protease Inhibitors in Children ≥2 y and ≥14 kg (CROI 2025) - P2/3 | "An ongoing Phase 2/3 open-label trial is evaluating F/TAF in combination with cobicistat-boosted atazanavir (ATV/co) or darunavir (DRV/co) in children with HIV-1 (NCT02016924). Changes in height, weight, and body mass index Z-scores; spine and TBLH BMD; and eGFR were not clinically significant (Table). Conclusions In this interim analysis, F/TAF in combination with ATV/co or DRV/co in children aged 2-<12 y and weighing 14-<40 kg was efficacious, with an acceptable safety profile and no renal, bone, or weight concerns, supporting further evaluation in pediatric populations."

Clinical • Human Immunodeficiency Virus • Infectious Disease • Pediatrics • CD4

Plasma CNS Tissue Markers in Heavily Treatment-Experienced PWH in the PRESTIGIO Registry (CROI 2025) - "In HTE, lower tau was associated with fostemsavir (p=.049) and doravirine use (p=.037) and lower GFAP with darunavir (p=.009). Conclusions Plasma CNS tissue marker levels do not support higher CNS injury risk in HTE-PWH. Several other variables seem independently and variably associated with higher levels of each marker."

CNS Disorders • Human Immunodeficiency Virus • Infectious Disease • Targeted Protein Degradation • CD4 • GFAP • NEFL • UBC

ART Exposure and Accelerated Aging in PLHIV: Insights From Proteomic and Methylation Clocks (CROI 2025) - P | "Longer cumulative exposure to dolutegravir (DTG), rilpivirine (RPV) and nelfinavir (NFV) was associated with lower age advancement scores on at least a biological clock. In contrast, longer exposure to tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), darunavir (DRV), atazanavir (ATV), and dideoxynucleoside analogues (d-drugs) was related to higher age advancement scores (Figure 1; P<0.05, adjusted for chronological age)...Conclusions Cumulative ART exposure influences age acceleration in PLHIV, with distinct effects across regimens and drug classes. Innate immune pathways appear to be key drivers of these effects and are promising therapeutic targets to mitigate accelerated aging."

Human Immunodeficiency Virus • Infectious Disease • Inflammation

Population PK and CYP3A Inhibition Capacity of Ritonavir in Pregnancy: A Model-Based Meta-Analysis (CROI 2025) - "Background Ritonavir (RTV), a strong CYP3A inhibitor, is widely used as a pharmacokinetic (PK) enhancer to increase exposure to HIV-1 protease inhibitors (PIs) and more recently the SARS CoV-2 PI nirmatrelvir...Methods Pregnant participants receiving RTV as a PK enhancer for either lopinavir, darunavir, or atazanavir±TDF and who were ≥20 weeks gestational age were included in the analysis...Decreased RTV exposures during pregnancy are predicted to lead to a 1.8-fold reduction in RTV-mediated CYP3A inhibition. Dosing requirements of RTV and/or boosted CYP3A substrates may be altered during pregnancy."

Retrospective data • Human Immunodeficiency Virus • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Genotypic Resistance in the African Paediatric CHAPAS-4 Trial of Second-Line Antiretroviral Therapy (CROI 2025) - "Background In the CHAPAS-4 trial of second-line antiretroviral therapy following NNRTI-based first-line, 96-week efficacy was superior for tenofovir alafenamide (TAF) vs standard-of-care (SOC: abacavir (ABC)/zidovudine (ZDV)), and for dolutegravir (DTG) vs ritonavir-boosted lopinavir (LPV/r)/atazanavir (ATV/r)...Methods Randomisation was simultaneously to TAF vs ABC/ZDV, and DTG vs darunavir (DRV/r) vs LPV/r vs ATV/r...Intermediate/high-level resistance to anchor was: 0/29 LPV/r, 4% (1/26) ATV/r (1 TAF/FTC), 0/18 DRV/r and 22% (2/9) DTG (2 ZDV/3TC)...Three children on ZDV/3TC (2 DTG,1 LPV/r) developed new high-level emtricitabine/lamivudine (FTC/3TC) resistance (M184V)...W96 intermediate/high-level anchor drug resistance was uncommon, and as in second-line adult and paediatric trials, resistance to DTG only occurred in children taking ZDV. These results will inform second-line treatment guidelines for children."

Clinical • Pediatrics

Neurodevelopmental Disorders in French HIV-/ARV-Exposed Uninfected Children: A National Cohort Study (CROI 2025) - "However, among those exposed to tenofovir-emtricitabine, the r-darunavir-based combination was significantly associated with a higher combined incidence of neurodevelopmental disorders and related specialized consultations than other protease inhibitors (log rank, p<0.001). Conclusions Children exposed in utero to ARV and HIV are at higher risk of neurodevelopmental disorders of multifactorial origin."

Clinical • Neurodevelopmental • CNS Disorders • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease • Psychiatry

Risk of Incident Hypertension With Common Antiretroviral Agent Combinations in the OPERA Cohort (CROI 2025) - "We estimated adjusted incidence rate ratios (aIRR; multivariate Poisson regression) comparing regimens of dolutegravir (DTG) 3DR with or without tenofovir alafenamide (TAF), DTG/lamivudine (3TC) 2DR, bictegravir/emtricitabine/TAF (B/F/TAF), or boosted darunavir (bDRV) 3DR with or without TAF. Conclusions In this real-world assessment of people with HIV with either n+eBP or nBP at regimen start, no statistically significant difference was observed between common core ARV agents with or without TAF and the rate of incident HTN in ART-naïve or ART experienced individuals. Among commonly used modern ART regimens, specific antiretroviral combinations do not appear to be a driving factor in the development of HTN in this large and diverse cohort of people with HIV in the US."

Cardiovascular • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Obesity

Structural Implications of HIV-1 Protease Subtype C Bound to Darunavir: A Molecular Dynamics Study. (PubMed, Proteins) - "This alters the overall structural compactness and the hydrophobic core crucial for drug binding. Subtle structural changes result in the loss of hydrogen bond interactions, reducing the binding energy of L38HL HIV-1 protease subtype C bound to DRV, leading to drug resistance."

Journal • Human Immunodeficiency Virus • Infectious Disease