Prezista (darunavir) / J&J - LARVOL DELTA

The dolutegravir failure cohort: A multi-country longitudinal cohort with a randomised clinical trial of continued dolutegravir versus switch to darunavir in people with viraemia while on dolutegravir in Sub-Saharan Africa (The Ndovu Study) protocol. (PubMed, PLoS One) - P, P3 | "The Ndovu study will address critical gaps in the management of DTG failure including the emergence, determinants and implications of DTG resistance. Further, it will evaluate the optimal ART regimens to use in the setting of DTG resistance in adults and children."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease

Atorvastatin suppresses HIV/antiretroviral drug-induced cardiac fibrosis and dysfunction in mice by blocking platelet TGFβ1 signaling. (PubMed, JCI Insight) - "In the REPRIEVE trial, pitavastatin reduces atherosclerotic CVD risk to a magnitude inconsistent with pitavastatin's impact solely on LDL-cholesterol and inflammation...ART drugs used in REPRIEVE, including a nucleoside/nucleotide, integrase inhibitor-based regimen (tenofovir (TDF), emtricitabine (FTC), and dolutegravir (DTG)), and the protease inhibitors ritonavir (RTV) and darunavir (DRV), and the impact of atorvastatin, were examined in two HIV mouse models: transgenic HIV-Tg26 mice and HIV-PDX mice engrafted with T cells isolated from PWH...Administration of TDF-FTC-DTG or RTV, but not DRV, resulted in a further ~2-fold increase in fibrosis (p<0.01)...Our results indicate that certain ART regimens accelerate HIV-associated CVD characterized by HFpEF via platelet TGFβ1-dependent processes, which were mitigated by atorvastatin. We postulate that our findings provide a potential mechanism for the pleiotropic effects of statins in HIV/ART-linked CVD which could be..."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation

Cardiometabolic impact of dolutegravir as second-line therapy: secondary analysis of a randomized controlled trial. (PubMed, AIDS) - P3b/4 | "Dolutegravir-based second-line regimens were associated with weight gain, which was further influenced by gender, ethnicity and HIV-related factors. DTG-based second-line regimens had no significant effect on blood pressure at 96 weeks; DTG + TDF/XTC was associated with a more favourable lipid profile than darunavir-containing regimens."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Dolutegravir restores gut microbiota in late-stage HIV-1 unlike darunavir: an open-label, randomized clinical trial. (PubMed, Nat Commun) - P4 | "After two years, participants on dolutegravir-based therapy had gut microbiota profiles more closely resembling those of people without HIV, compared to individuals taking darunavir/ritonavir. In summary, dolutegravir-based therapy restores the gut microbiota more effectively than darunavir/ritonavir in patients who present late with HIV."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease • Inflammation • CD4

Anion-Controlled Structural Interconversion of Palladium Cages Enables Separations by Selective Guest Capture and Release. (PubMed, Angew Chem Int Ed Engl) - "To showcase the power of this supramolecular catch-and-release purification, we designed and validated a closed-loop purification process, successfully isolating Darunavir from a complex mixture of pharmaceutical molecules with exceptional selectivity and efficiency. This work highlights a broadly applicable strategy for advanced molecular separations and selective pharmaceutical purification."

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Dosing of ritonavir-boosted darunavir for treatment of HIV in pregnancy. (PubMed, AIDS) - "This analysis provides some reassurance that once-daily DRV/r can be used successfully in pregnancy. However, given the possibility of reduced drug levels in pregnancy with once-daily dosing, viral load monitoring during pregnancy remains essential. Surveillance of pregnancies in women receiving once-daily DRV/r is needed to further support the use of this dosing during pregnancy."

Journal • Human Immunodeficiency Virus • Infectious Disease

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."

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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