lopinavir/ritonavir / Generic mfg. - LARVOL DELTA

Population pharmacokinetic/pharmacodynamic modelling to evaluate favipiravir in combination with lopinavir-ritonavir in patients with COVID-19. (PubMed, Br J Clin Pharmacol) - "Our findings suggest that favipiravir does not have antiviral activity at the dose used in our study, and further work to understand the mechanistic basis of the drug-drug interaction with lopinavir-ritonavir is required."

Clinical • Journal • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (clinicaltrials.gov) - P3 | N=10000 | Recruiting | Sponsor: UMC Utrecht | Phase classification: P4 ➔ P3 | N=7100 ➔ 10000 | Trial completion date: Dec 2023 ➔ Dec 2025 | Trial primary completion date: Dec 2021 ➔ Dec 2023

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Infectious Disease • Influenza • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (clinicaltrials.gov) - P4 | N=6800 | Recruiting | Sponsor: MJM Bonten | N=4000 ➔ 6800 | Trial completion date: Feb 2019 ➔ Jun 2022 | Trial primary completion date: Feb 2019 ➔ Dec 2021 | Initiation date: Dec 2015 ➔ Apr 2016

Enrollment change • Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Influenza • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (clinicaltrials.gov) - P4 | N=7100 | Recruiting | Sponsor: MJM Bonten | Trial completion date: Jun 2022 ➔ Dec 2023

Trial completion date • Infectious Disease • Influenza • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (clinicaltrials.gov) - P4 | N=4000 | Recruiting | Sponsor: UMC Utrecht

New P4 trial • Infectious Disease • Influenza • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (clinicaltrials.gov) - P3 | N=10000 | Recruiting | Sponsor: UMC Utrecht | Trial completion date: Dec 2025 ➔ Feb 2028 | Trial primary completion date: Dec 2023 ➔ Feb 2026

Trial completion date • Trial primary completion date • Infectious Disease • Influenza • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

REMAP-CAP: Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (clinicaltrials.gov) - P3 | N=20000 | Recruiting | Sponsor: UMC Utrecht | N=10000 ➔ 20000

Enrollment change • Infectious Disease • Influenza • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Body Composition Changes in Children Living With HIV Initiated on Dolutegravir or Protease Inhibitors in the CHAPAS-4 Trial. (PubMed, Pediatr Infect Dis J) - "DTG and ATV/r were associated with greater gains in fat-free mass and muscle mass than LPV/r, while DRV/r, TAF and prior nevirapine exposure were associated with fat mass accrual. Fat gain may initially reflect return to health but sustained increases may have metabolic implications. These findings suggest the need to monitor fat compartments with long-term exposure."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Oral Lamivudine for Extended HIV Postnatal Prophylaxis. (PubMed, Paediatr Drugs) - "The antiretroviral drugs most commonly studied as ePNP, either alone or in combination, are lamivudine, nevirapine, lopinavir/ritonavir and zidovudine. Guided by maternal HIV viral load, ePNP may be particularly indicated, as it could ensure that the prophylaxis provides the greatest benefit/risk to children at highest risk. Long-acting injectable antiretroviral drugs and broadly neutralising antibodies (bNAbs) have yet to be fully evaluated in neonates, infants and children; however, they may offer new alternatives in the future."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Longitudinal changes in bone mineral density among children living with HIV over 96 weeks following switch to second-line antiretroviral therapy in Uganda. (PubMed, PLOS Glob Public Health) - "CLWH aged 3-15 years switched to second-line ART including tenofovir alafenamide fumarate-emtricitabine (TAF/FTC) or standard-of-care (SOC) (abacavir (ABC) or zidovudine (ZDV) with dolutegravir (DTG), atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r)...-0.30,95% CI: -0.46, -0.15], p < 0.001) and first-line nevirapine (NVP) exposure (-0.25,95% CI: -0.43, -0.06, p = 0.009)...Smaller declines in TBLH BMD were associated with higher baseline fat mass, higher LS HA BMD, and use of DRV/r, DTG, or ATV/r compared with LPV/r. These findings emphasize the importance of ART selection and body composition in supporting bone health among CLWH."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

Effects of Ritonavir, Lopinavir, and Alcohol on ABC Transporters and Secretion of Bile Acid and Bilirubin in Senescent Hepatocytes. (PubMed, Int J Mol Sci) - "In this study, the toxic effects of ritonavir, lopinavir, and alcohol on hepatocyte transporters and the secretion of bile acids and bilirubin were investigated in hydrogen peroxide-induced senescent HepG2 and doxorubicin-induced senescent primary human hepatocytes. Further, anti-cholestasis agents, ursodeoxycholic acid and glycyrrhizin, significantly ameliorated the impaired secretions of bile acids and bilirubin as well as reducing intracellular lipid accumulation and cell death caused by ritonavir, lopinavir, and alcohol in the primary hepatocytes with ABCC6 knockdown. These results indicate that senescence moderately impairs the ABC transporters of hepatocytes and secretion of bile acids or bilirubin, which become worse in the presence of the drugs and alcohol but could be improved by anti-cholestasis agents."

Journal • Addiction (Opioid and Alcohol) • Cholestasis • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Liver Failure • ABCB1 • ABCB4 • ABCC1 • ABCC2 • ABCC3 • ABCC6 • ABCD3 • LMNA • UGT1A1

High Viral Suppression Rates and Attrition Rates Among Children With Perinatally Acquired HIV in the Thai National AIDS Program, 2023. (PubMed, Pediatr Infect Dis J) - "Children diagnosed with HIV through EID and linked to the Thai NAP had promising 7-year survival rates but substantial LTFU. Strategies to improve retention and re-engagement in care and are essential for better outcomes."

Journal • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Triple drug co-delivery within nanosystems for synergistic anti-infective, anti-inflammatory, antinociceptive and neuroregenerative therapeutic effects: a focus on pharmacological and nanotechnological aspects. (PubMed, Eur J Pharmacol) - "Triple drug co-encapsulation has been achieved for non-steroidal anti-inflammatory drugs such as indomethacin, analgesic and antipyretic drugs such as paracetamol, immunosuppressant drugs such as methotrexate, antiretroviral drugs such as efavirenz, lopinavir, ritonavir, and tenofovir, antibacterial drugs such as amoxicillin and clarithromycin, antiulcer drugs such as omeprazole and famotidine, ion channel antagonists such as lomerizine hydrochloride, oxidized adenosine triphosphate, and zonampanel monohydrate, photosensitive molecules such as indocyanine green, genetic material such as MMP-9 siRNA, enzymes such as catalase, and/or plant-derived bioactive compounds such as curcumin, resveratrol, sinomenine, and thymoquinone. These molecules' triple co-encapsulation into nanometric formulations has led to controlled and sustained drug release, extended circulation time, enhanced bioavailability, and reduced systemic toxicity, with an overall improvement in drug..."

Journal • Review • Dermatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Mood Disorders • Pain • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • CAT • MMP9

Weight gain, body composition, and metabolic parameters of dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: an ancillary analysis of the ODYSSEY trial. (PubMed, Lancet Child Adolesc Health) - P2/3 | "Over approximately 5 years, indices defining excessive weight gain and central adiposity were similar with dolutegravir and other anchor drugs, and lipid and glycaemia profiles with dolutegravir were reassuring, providing supporting evidence for dolutegravir-based ART as the preferred treatment in children and adolescents."

Journal • Human Immunodeficiency Virus • Infectious Disease • Obesity

A Case of HIV Encephalopathy with HIV Cerebrospinal Fluid Escape followed by Second-Generation Integrase Inhibitor Resistance. (PubMed, Int J Infect Dis) - "A 61-year-old male with advanced HIV (CD4+ T-cell count 31 cells/μL) initiated antiretroviral therapy with bictegravir/emtricitabine/tenofovir alafenamide...His regimen was switched to zidovudine/lamivudine/lopinavir/ritonavir, leading to dramatic clinical improvement, undetectable CSF HIV-RNA, and reduced leptomeningeal enhancement on magnetic resonance imaging...It demonstrates that sanctuary site-specific resistance can develop against key first-line regimens, highlights the need for a revised approach. CSF viral load quantification and resistance genotyping are essential in such scenarios to guide effective, personalized therapy."

Journal • CNS Disorders • Herpes Zoster • Human Immunodeficiency Virus • Infectious Disease • Varicella Zoster • CD4

Tolerability of lopinavir versus dolutegravir in children and adolescents with HIV (LoDoCA): a prospective cohort study in lesotho, Southern Africa. (PubMed, AIDS) - "Observed treatment satisfaction and tolerability support the rollout of DTG in pediatric HIV care."

Journal • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Reassessing the Conduct of Patch Clamp Cardiac Ion Channel Assays to Improve Nonclinical Data Translation to Clinical ECG Changes and Proarrythmia Risk. (PubMed, Clin Transl Sci) - "Finally, astemizole, risperidone, and clarithromycin-"intermediate TdP risk" CiPA drugs-were reported to have hERG-active metabolites, yet hERG data for metabolites were not integrated when developing in silico human myocyte models for risk prediction...Here the effects of chloroquine, lopinavir, ritonavir, and vanoxerine on hERG, CaV1.2, and/or NaV1.5 channels were studied using protocols consistent with ICH S7B Q&A 2.1 best practices...The results showed improved alignment between ion channel block profiles and drug-induced ECG changes and proarrhythmia, underscoring the importance of using physiologically relevant experimental protocols, accounting for ion channel-active metabolites, and continuing to build the knowledge base of arrhythmogenesis mechanisms. Data may be found at: https://osf.io/7rfua/."

Journal • Cardiovascular • NAV1

Lopinavir/ritonavir induces hepatotoxicity in HepG2 cells through inhibition of the Nrf2 pathway, resulting in oxidative stress, endoplasmic reticulum stress, and cell cycle arrest. (PubMed, Toxicol Lett) - "Collectively, our findings demonstrate that LPV/r suppresses Nrf2 and HO-1 protein, promotes ROS accumulation, which induces oxidative stress and ER stress, ultimately leading to cell apoptosis and G0/G1 phase cell cycle arrest. This research provides novel mechanistic insights into the hepatotoxic effects of LPV/r."

Journal • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Liver Failure

A preliminary survey on the use of ART among blood donors in Shenzhen China and its implications to blood safety. (PubMed, BMC Infect Dis) - "ART drugs were detected in 4(4/100) anti-HIV reactive plasma samples screened from 440 000 donations in Shenzhen, which indicated some HIV-infected people who take ART drugs donate blood without disclosing their health and medical histories and this may endanger blood safety because ART may compromise current screening strategies by suppressing HIV RNA replication below the detectable level."

Journal • Human Immunodeficiency Virus • Infectious Disease

DB-1311-O-1001: A Phase 1/2a Study of DB-1311/BNT324 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=862 | Recruiting | Sponsor: DualityBio Inc. | Trial completion date: Jan 2028 ➔ May 2028 | Trial primary completion date: Sep 2027 ➔ Dec 2027

First-in-human • Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • BRAF • CD276 • EGFR • KRAS • MET • NTRK1 • NTRK2 • NTRK3 • ROS1

Risk factors associated with anti-tubercular therapy-induced hepatitis in human immunodeficiency virus seropositive and seronegative patients in India. (PubMed, Int J Risk Saf Med) - "The prevalence of ATT-IH in HIV-SPP was 53.6% and 46.4% in HIV-SNP. A higher incidence of 23 (10 %) of ATT-IH was reported with the Tenofovir + Lamivudine + Lopinavir+ Ritonavir ART regimen.ConclusionClinicians must focus on early detection of risk factors for ATT-IH in HIV-SPP in comparison with HIV-SNP to prevent significant hepatic complications."

Journal • Hepatitis B • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Therapeutic potential of spiramycin-nanoparticles and Aluvia in experimental congenital toxoplasmosis. (PubMed, Exp Parasitol) - "In conclusion, spiramycin-loaded CSNPs and Aluvia demonstrated low parasite burden and successfully restored normal brain architecture in the offspring. However, congenital anomalies persisted and remained a significant concern."

Journal • Infectious Disease

The Prevalence and Determinants of Dyslipidemia and Lipodystrophy in Children on Highly-Active Antiretroviral Therapy at a Ghanaian Teaching Hospital: A Cross-Sectional Study. (PubMed, J Int Assoc Provid AIDS Care) - "Participants with lipodystrophy had lower odds of elevated triglycerides (OR: 0.1; 95% CI: 0.00-0.62 P = .029). Previous lopinavir/ritonavir use was significantly associated with reduced odds of dyslipidemia (OR: 0.21; 95% CI: 0.05-0.91, P = .036).ConclusionThe high prevalence of dyslipidemia and lipodystrophy emphasizes the need for routine lipid and other metabolic assessments among children and adolescents living with HIV."

Journal • Observational data • Cardiovascular • Dyslipidemia • Human Immunodeficiency Virus • Hypertriglyceridemia • Infectious Disease • Lipodystrophy • Metabolic Disorders

Safety Profile of COVID-19 Medication in Patients with CKD: Renal and Hepatic Dysfunction Associated with Antiviral and Tocilizumab Use, a Single-Centre Experience (KIDNEY WEEK 2025) - "Methods We conducted a retrospective study on 1425 COVID-19-infected patients, who received anti-viral therapy, i.e., Favipiravir, lopinavir-Ritonavir, Remdesivir and tocilizumab. Conclusion CKD patients had a significantly higher incidence of renal function deterioration and an increase in AST. Nevertheless, these abnormal lab parameters must be considered with other risk factors, associated with severe covid-19-infection, thus COVID medicine shouldn't be denied to CKD patients"

Clinical • Chronic Kidney Disease • Hepatology • Infectious Disease • Liver Failure • Nephrology • Novel Coronavirus Disease • Renal Disease

Efficacy and safety of switching from lopinavir/ritonavir-based regimens to bictegravir/emtricitabine/tenofovir alafenamide in people living with HIV: A multicenter retrospective study. (PubMed, Virol Sin) - "These PLWH typically have a history of either treatment failure or intolerance to first-line efavirenz-based regimens. The median triglyceride level decreased from 2.4 mmol/L to 1.8 mmol/L (P < 0.001), while no difference in CD4 counts was observed. These findings demonstrate that BIC/FTC/TAF is an effective and metabolically favorable treatment option for PLWH switching from LPV/r based regimens, regardless of whether they have a prior history of virological failure."

Journal • Retrospective data • Human Immunodeficiency Virus • Infectious Disease • CD4