Prezista (darunavir) / J&J - LARVOL DELTA

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

The clinical and economic impact of genotypic resistance testing for people diagnosed with persistent virological non-suppression on tenofovir-lamivudine-dolutegravir in South Africa: a modelling study. (PubMed, Lancet HIV) - "GRT could increase life expectancy for people with HIV and persistent virological non-suppression on TLD in South Africa and could be cost-effective, especially at lower test costs. At current effectiveness and costs of tenofovir-lamivudine plus ritonavir-boosted darunavir, an immediate switch would not be preferred."

HEOR • Journal • Allergy • Human Immunodeficiency Virus • Immunology • Infectious Disease

Laser Microinterferometry for API Solubility and Phase Equilibria: Darunavir as a Case Example. (PubMed, Pharmaceutics) - " Using laser microinterferometry, the thermodynamic solubility and phase behavior of amorphous darunavir were determined in various pharmaceutical solvents, including vaseline and olive oils, water, glycerol, alcohols (methanol, ethanol, isopropanol), glycols (propylene glycol, polyethylene glycol 400, polypropylene glycol 425, polyethylene glycol 4000), and ethoxylated polyethylene glycol ether obtained from castor oil in the temperature range of 25-130 °C. This method allows for directly observing the dissolution process, determining the solubility limits, and detecting phase transitions. These studies are necessary for selecting appropriate excipients, preventing the formation of undesirable solvates and predicting formulation stability, which are all critical factors in early-stage drug development and pharmaceutical formulation design."

Journal

The Meandrous Route of Rilpivirine in the Search for the Miraculous Drug to Treat HIV Infections. (PubMed, Viruses) - "For this purpose, it was subsequently combined with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), darunavir (boosted with ritonavir or cobicistat) or dolutegravir. Its wide-spread use is thanks to its combination with cabotegravir (CAB) in the form of a long-acting intramuscular injection once per month (QM), later twice per month (Q2M), for the treatment of adults, later extended to adolescents and pregnant women, with HIV infections. The long-acting CAB plus RPV should not be administered in patients treated with rifampicin or rifabutin, patients with virological failure or patients with resistance to CAB or RPV, or patients with hepatitis B virus (HBV) infection. Long-acting CAB+RPV may lead to pain at the site of injection which would diminish over time."

Journal • Review • Hepatitis B • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Pain

Chiral Epoxy-Imine Building Block for Diversity-Oriented Synthesis of Peptidomimetic Aspartic Protease Inhibitors. (PubMed, J Org Chem) - "Subsequent epoxide cleavage with a suitable amine delivers anti-1,3-diaminopropan-2-ol derivatives. The suitability of the developed building block for step economy approach to peptidomimetic aspartic protease inhibitors was demonstrated by concise seven-step synthesis of anti-HIV darunavir."

Journal • Human Immunodeficiency Virus • Infectious Disease

Pharmacokinetic modeling to support WHO-weight band dosing of the new pediatric Darunavir/ritonavir (120/20 mg) fixed-dose combination tablet for children (IAS-HIV 2025) - "The model-based dosing of the new pediatric DRV/r FDC tablets supports once- and twice-daily dosing according to WHO weight bands in children aged =3 years and weighing 10 to <35 kg."

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

Comparative effectiveness of modern antiretroviral therapy regimens among people living with HIV in China: a multicenter cohort study (IAS-HIV 2025) - "Most frequently used third ART drugs included nevirapine, efavirenz, dolutegravir, lopinavir, and others (including darunavir, raltegravie, elvitegravir and rilpivirine). Our findings further reinforce the positioning of dolutegravir-based regimens as preferred options in LMICs."

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

Age-dependent oral drug absorption in children: Assessment of a bottom-up modelling approach. (PubMed, Eur J Pharm Biopharm) - "This study aimed to refine PBPK modelling for paediatric applications by developing a customized PK-Sim-based paediatric PBPK (pPBPK) model for four drugs that are part of the Model List of Essential Medicines for Children by the World Health Organisation: paracetamol, ibuprofen, darunavir, and itraconazole. Sensitivity analyses highlighted the influence of gastric emptying time, small intestinal transit, and bile salt concentration on drug pharmacokinetics. This research underscores the potential of pPBPK modelling to inform paediatric dosing strategies while addressing current gaps and challenges."

Journal • Pediatrics

Design, synthesis, evaluation and X-ray structural studies of potent HIV-1 protease inhibitors containing substituted oxaspirocyclic carbamates as the P2 ligands. (PubMed, Eur J Med Chem) - "One of these inhibitors displayed subnanomolar HIV-1 protease affinity and also exhibited potent antiviral activity. A high-resolution X-ray crystal structure of this inhibitor-bound HIV-1 protease show that the oxaspirocyclic P2 ligand forms an unconventional C-H⋯O bond with the backbone carboxyl group of Gly48' and an interesting N-H … π interaction with the aromatic ring in the S2 subsite of HIV-1 protease active site."

Journal • Human Immunodeficiency Virus • Infectious Disease