Prezista (darunavir) / J&J - LARVOL DELTA

Phenotypic impacts of treatment-selected mutations in HIV-2 protease on darunavir and lopinavir susceptibility: Evaluating genotypic HIV-2 drug resistance tools. (PubMed, PLOS Glob Public Health) - "We provide phenotypic evidence supporting the resistance role of changes in HIV-2 protease which do not have HIV-1 analogues, as well as evidence that analogues of "major" resistance changes in HIV-1 may have no resistance impacts in HIV-2, despite apparent treatment selection. These results should inform the HIV-2 genotypic resistance tools and help improve treatment for PLWH2."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Virological outcomes with Bictegravir/Emtricitabine/Tenofovir alafenamide (B/F/TAF) in people previously treated with darunavir-based antiretroviral therapy. (PubMed, HIV Med) - "Substituting of Darunavir-based ART with B/F/TAF in this challenging population was associated with treatment-emergent INSTI and NRTI resistance. Historical resistance did not predict virological outcomes and treatment-emergent resistance did not preclude re-suppression on B/F/TAF, suggesting that adherence remains a major barrier to achieving long-term virological success."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Reversible Effects of Integrase Inhibitors on Newly Differentiated Adipocytes. (PubMed, Viruses) - "Thus, we examined the effects of the INSTI, Dolutegravir (DTG), on human adipose cells in vitro and the reversibility of these effects by switching to a protease inhibitor, Darunavir (DRV). Exposure to DTG during differentiation lowered triglyceride accumulation and adiponectin secretion without altering the expression of adipogenic markers. Thus, DTG exposure resulted in changes in adipocyte function consistent with the progression of metabolically adverse phenotypes, and these effects were reversible."

Journal • Human Immunodeficiency Virus • Infectious Disease • LEP

Regional variations of rates and determinants of drug resistance mutations in people failing first-line therapy for HIV-1: a substudy from the D2EFT phase 3b/4 clinical trial. (PubMed, Clin Infect Dis) - "The regional specificity of mutations underscores the dynamic nature of HIV-1 drug resistance patterns and the importance of monitoring and understanding local mutation profiles."

Clinical • Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease

Designing Potent HIV‑1 Protease Inhibitors Using Machine Learning and QSAR Approaches. (PubMed, ACS Omega) - "Darunavir, a second-generation protease inhibitor, has reduced efficacy against resistant HIV-1 variants, underscoring the development of new inhibitors...Furthermore, molecular docking suggested that B03 and B05 exhibit strong binding interactions with wild-type and variants, particularly through hydrophobic and hydrogen bonding interactions, with key residues including D25, G27, D29, D30, D25', and D30'. This integrated QSAR-ML and structure-based analysis offers promising candidates for addressing drug resistance."

Journal • Human Immunodeficiency Virus • Infectious Disease

Highly Potent Phosphinic HIV‑1 Protease Inhibitors: Synthesis, In Vitro Evaluation, and Docking Studies. (PubMed, ACS Omega) - "Among them, the PAC-Phe-Val derivative (9c) demonstrated potent inhibition, with an IC50 value of 33 nM, comparable to the FDA-approved Darunavir...This work highlights the potential of symmetrical phosphinic pseudopeptides as HIV-1 protease inhibitors and provides a foundation for further development of these compounds as novel antiretroviral therapies. Future research will focus on optimizing the pharmacokinetic properties and evaluating resistance profiles, aiming to advance the next generation of HIV treatments."

Journal • Preclinical • Human Immunodeficiency Virus • Infectious Disease

Fluorinated HIV-1 protease inhibitors containing chiral hydroxyethylbenzene and indanol as P2' ligands with potent activity against drug-resistant variants. (PubMed, Eur J Med Chem) - "A series of darunavir analogs were designed by incorporating chiral 4-(1-hydroxyethyl)benzene and 1-indanol moieties as P2' ligands, in combination with P1 fluorination...To maintain polar interactions in the S2' subsite of HIV-1 protease, the orientation of the (R)-indanol moiety was flipped relative to the (S)-1-indanol moiety. The SAR data and structural analysis offer insights for further optimization to improve potency against drug-resistant HIV-1 variants."

Journal • Human Immunodeficiency Virus • Infectious Disease

Darunavir analog precursors target mitochondrial metabolism in multiple myeloma and CLL. (PubMed, Cancer Cell Int) - "BupM-NH2, and particularly BnpM-NH2, showed enhanced cytotoxicity against MM, CLL, and NDMM cells compared to PBMCs by inducing apoptosis through autophagy and mitochondrial respiration inhibition. While the cytotoxic effect in RRMM is less pronounced and nonsignificant, BupM-NH2 and BnpM-NH2 induces stress in respiratory chain and mitochondria, which may re-sensitize resistant tumor cells to treatments. Therefore these compounds may hold promise as novel therapeutic agents for MM and CLL treatment."

Journal • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Multiple Myeloma • Oncology • ANXA5

Coadministration of a crystalline drug compromises supersaturation and membrane transport of an amorphous drug. (PubMed, Int J Pharm) - "Non-sink dissolution studies were conducted for a physical mixture of amorphous atazanavir and crystalline darunavir. This suggests that water facilitated mixing of the drugs in the colloidal phase, which affected the release and membrane transport properties of atazanavir. These findings further illustrate the complexity of formulating or co-administrating multicomponent drugs, even when present in different solid forms, and provide new insights into how amorphous drugs behave when co-administered with crystalline drugs."

Journal

Repurposing HIV-Protease Inhibitor Precursors as Anticancer Agents: The Synthetic Molecule RDD-142 Delays Cell Cycle Progression and Induces Autophagy in HepG2 Cells with Enhanced Efficacy via Liposomal Formulation. (PubMed, Int J Mol Sci) - "In this study, we investigated the antiproliferative activity of RDD-142, a synthetic precursor of the HIV-1 protease inhibitor (HIV-PI) Darunavir analog, on the human hepatocellular carcinoma line (HepG2) and healthy hepatocyte line (IHH), both as a free molecule and in liposomal formulation...These effects were linked to RDD-142 inhibitory activity on the chymotrypsin-like subunit of the proteasome, triggering a UPR-mediated stress response...RDD-142 demonstrated promising potential as a therapeutic agent for HCC. Its antitumor activity may be further amplified through liposomal nanoformulation, offering a successful strategy to reduce effective dosage and minimize adverse effects."

Journal • Hepatocellular Cancer • Human Immunodeficiency Virus • Infectious Disease • Oncology • Solid Tumor

Beyond General HIV Risk: Insights on Antiretroviral Agents, Immune Status, and Cardiovascular Disease Progression in a Vulnerable Urban Cohort (AHA 2025) - "After adjustment, tenofovir use was associated with decreased CAD progression (aOR 0.14, 95% CI 0.03–0.69, p<0.05), while raltegravir (aOR 49.40, CI 1.84–1326.57, p<0.05), cobicistat (aOR 23.57, CI 1.31–425.58, p<0.05), cocaine use (aOR 13.52, CI 2.09–87.60, p<0.01), male sex (aOR 8.55, CI 1.24–59.12, p<0.05), and obstructive sleep apnea (aOR 25.23, CI 2.15–296.64, p<0.05) were associated with increased risk. Specific ART agents and CD4 count were independently associated with distinct CVD outcomes alongside traditional cardiovascular risk factors in this cohort. These insights support considering individual ART and immune status for tailored CVD risk assessment in vulnerable populations with HIV."

Cardiovascular • Coronary Artery Disease • Human Immunodeficiency Virus • Infectious Disease • Myocardial Infarction • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder • CD4

Insights from systematic reviews (2019-2024) and drug interaction database analysis in people with HIV and comorbidities. (PubMed, Int J STD AIDS) - "Severe adverse drug reactions associated with ARTs, including efavirenz, darunavir, nevirapine, and atazanavir-ritonavir, especially when combined with treatments for TB and malaria. Key interactions included reduced drug levels from rifampicin and QT prolongation from artemether-lumefantrine...Database discrepancies were noted, especially for riociguat interactions and ritonavir through inhibition of P-gp or OATP1B1 functions.ConclusionsDDIs in PWH receiving ART with comorbidities have highlighted the crucial need for personalized treatment. Incorporating pharmacokinetic, pharmacodynamic, and pharmacogenomic factors is essential for optimizing therapy outcomes."

Journal • Cardiovascular • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Malaria • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Design, Synthesis, and Biological Evaluation of Novel Core Scaffold-Modified HIV-1 Protease Inhibitors for Overcoming Drug Resistance. (PubMed, J Med Chem) - "Furthermore, it maintained excellent potency against the multidrug-resistant variants (EC50 = 30 ∼ 34.3 nM), demonstrating a superior resistance profile relative to Darunavir...Subsequent investigations indicated that compound 20a-D, the dipeptide prodrug of 20a, exhibited improved ADME properties. Consequently, this study highlighted the potential of core scaffold modification in generating candidates to overcome multidrug resistance and provided valuable information for further optimization."

Journal • Human Immunodeficiency Virus • Infectious Disease

High Effectiveness and Rare Virologic Failure in Treatment-Experienced Individuals on Long-Acting Cabotegravir + Rilpivirine Therapy Across Europe: Insights from the EuroSIDA Study (EACS 2025) - "Two individuals experienced CVF with no resistance testing, switched to boosted darunavir-based regimens, and resuppressed to VL<50 copies/mL. Virologic suppression was consistent across BMI categories. These real-world data support prior studies demonstrating durable effectiveness and tolerability of CAB+RPV/LA."

Clinical • Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

Outcomes of HIV-Exposed Uninfected Children Born to HIV-Positive Mothers at Bichat-Claude Bernard Hospital: The ENIVIH Study (EACS 2025) - "Among children with events, in utero ARV exposures included zidovudine (4.1%), emtricitabine (46.2%), darunavir (35.9%), and abacavir (4.8%). These frequencies appear higher than those typically reported in the general pediatric population. The findings highlight the importance of long-term follow-up and integrated medical and social for HEU children."

Clinical • Human Immunodeficiency Virus • Infectious Disease

Comparable efficacy but greater discontinuations due to adverse events with dolutegravir-containing two-drug versus three-drug antiretroviral therapy: a systematic review and meta-analysis (EACS 2025) - "We assessed three prespecified subgroups: dolutegravir/lamivudine (DTG/3TC); dolutegravir/rilpivirine (DTG/RPV) and dolutegravir/ritonavir-boosted-darunavir (DTG/DRV/r). There were more discontinuations due to AEs with 2DR. However, the effect of switch studies may have contributed to this."

Adverse events • Retrospective data • Review • Human Immunodeficiency Virus • Infectious Disease • CD4

Predicting the Impact of Drug Resistance Mutations on Inhibitor Potency with Molecular Dynamics and Machine Learning. (PubMed, J Phys Chem B) - "In this study we are using a very potent inhibitor, darunavir, bound to a series of 28 variants of HIV-1 protease with affinities from picomolar to micromolar, to develop an accurate method for predicting resistance...The best performing models included only physics-based features of intramolecular interactions, with four specific features largely distal from the active site sufficient to predict binding affinity within 1 kcal/mol of the experimental value, far better than models based on either the structures or sequences alone. Thus, we demonstrate a strategy to robustly predict the loss of binding potency due to unseen drug-resistance mutations."

Journal • Human Immunodeficiency Virus • Infectious Disease • Oncology

Cardiovascular Risk Assessment Using the Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score Model After Continuing or Switching to a Doravirine-Based HIV Treatment Regimen. (PubMed, J Acquir Immune Defic Syndr) - P3 | "After ∼4 years, DOR-based regimens were not associated with changes in ASCVD risk scores in PLWH. Given the increased burden of HIV-associated ASCVD, DOR may represent a therapeutic option that does not increase ASCVD risk."

Journal • Atherosclerosis • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease

Immune reconstitution in very advanced HIV patients treated with Dolutegravir vs Darunavir-based triple antiretroviral therapy. The Advanz-4 randomized clinical trial. (PubMed, Clin Microbiol Infect) - P4 | "DTG/3TC/ABC is safe and efficacious in very advanced ART-naïve HIV+ patients, induced a faster virological response, and was superior to the DRV/r regimen in reducing inflammation and bacterial translocation markers at 48 weeks."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease • Inflammation • TNFA

Virological Effectiveness of Dolutegravir Plus Darunavir in People with Multi-Drug-Resistant HIV: Data from the PRESTIGIO Registry. (PubMed, Viruses) - "DTG + DRV/b regimens were associated with a significantly lower risk of virological failure, even when drug activity was partial. This strategy remains a valuable option for managing multi-drug-resistant HIV."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Population pharmacokinetics of ritonavir as a booster of lopinavir, atazanavir, or darunavir in African children with HIV. (PubMed, Antimicrob Agents Chemother) - "We conducted a pharmacokinetic sub-study within the CHAPAS-4 (ISRCTN22964075) trial, which randomized children to two NRTIs with twice-daily lopinavir/ritonavir, once-daily atazanavir/ritonavir, or once-daily darunavir/ritonavir, as second-line ART. Ritonavir exposure is higher with atazanavir than with lopinavir or darunavir. These data provide greater insight into the use of ritonavir for boosting PIs in children and help reduce the knowledge gap regarding its exposure in children."

Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Evaluation of HIV-1 DNA resistance evolution in highly treatment-experienced and multi-resistant individuals under suppressive antiretroviral therapy: a longitudinal study from the PRESTIGIO Registry. (PubMed, J Antimicrob Chemother) - "Over a year, HIV-1 DNA MRM generally remained unchanged in suppressed HTE MDR people with HIV (PWH) except for a significant decline in M184V and a reduction of NNRTI resistance in the absence of NNRTI pressure."

Journal • Observational data • Tumor mutational burden • Human Immunodeficiency Virus • Infectious Disease • CD4 • TMB

Effectiveness of simplifying antiretroviral therapy to maintain viral suppression and improve bone and renal health: comparing simplified and non-simplified therapy. (PubMed, Braz J Infect Dis) - "These findings suggest that simplified therapy is as effective as triple therapy and has the additional benefit of reducing tenofovir-related adverse events."

Journal • Human Immunodeficiency Virus • Infectious Disease • Osteoporosis • Rheumatology

Efficacy and safety of emtricitabine/tenofovir alafenamide (F/TAF) plus cobicistat-boosted protease inhibitors in children with HIV-1 aged 2-<12 years and weighing 14-<40 kg: Week 48 outcomes (IAS-HIV 2025) - P2/3 | "BACKGROUND: TAF is a nucleoside reverse transcriptase inhibitor with improved renal and bone safety compared with tenofovir disoproxil fumarate. F/TAF is approved in Europe and the US for use with boosted protease inhibitors in adults and older children, and is being evaluated with cobicistat-boosted atazanavir (ATV/co) or darunavir (DRV/co) in younger children in an ongoing open-label Phase 2/3 trial (NCT02016924)... Over 48 weeks of treatment, F/TAF + ATV/co or DRV/co in children aged 2-<12 years and weighing 14-<40 kg maintained high rates of virologic suppression, with an acceptable safety profile. There were no renal, bone, or weight gain/loss concerns, supporting further evaluation of these drug combinations in pediatric populations."

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

Cost-effectiveness of Different Antiretroviral Treatment in Patients HIV Naive (clinicaltrials.gov) - P4 | N=0 | Withdrawn | Sponsor: Juan A. Arnaiz | N=150 ➔ 0 | Unknown status ➔ Withdrawn

Enrollment change • HEOR • Trial withdrawal • Human Immunodeficiency Virus • Infectious Disease • CD4