Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) / J&J, Gilead - LARVOL DELTA

Integrase versus protease inhibitor therapy in advanced HIV disease (LAPTOP): a multicountry, randomised, open-label, non-inferiority trial. (PubMed, Lancet Infect Dis) - P3 | "In people with advanced HIV disease, bictegravir, emtricitabine, and tenofovir alafenamide was shown to be non-inferior to darunavir, cobicistat, emtricitabine, and tenofovir alafenamide and resulted in fewer adverse events, supporting its use as a preferred first-line antiretroviral regimen in this vulnerable population."

Head-to-Head • Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

High-level multi-class transmitted antiretroviral resistance in a man with newly acquired HIV. (PubMed, Int J STD AIDS) - "A 19 year old man was diagnosed newly acquired HIV and prescribed bictegravir/emtricitabine/tenofovir alafenamide at his initial visit for HIV care...Although he had an initial substantial decline in viremia in the first 4 weeks, it was felt that the risk of subsequent failure was too high, and his antiretroviral treatment (ART) regimen was therefore changed to daily dolutegravir and darunavir/cobicistat/emtricitabine/tenofovir alafenamide, plus injected lenacapavir. He had durable virologic suppression on this new regimen for 12 months as of his last follow-up. This case of high-level multi-class transmitted drug resistance, in the context of rapid emergence of resistance to dolutegravir where it has been used as part of a salvage regimen, suggests that assessing for RAM in the integrase gene should be added to the currently recommended resistance testing for all patients with newly acquired HIV prior to initiating ART."

Journal • Human Immunodeficiency Virus • Infectious Disease

Viral Sabotage: HBV Reactivation in the Shadow of HIV (ACG 2025) - "Introduction: This is a case report of a 57 year old gentleman who presented to a tertiary medical center in acute liver failure due to reactivation of hepatitis B virus (HBV) after not taking his Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide) for four months. Treatment with Biktarvy and lactulose was initiated, and within 6 days, hepatic function recovered and mental status improved to baseline. HIV medication has antiviral effects on HBV, when HIV antiretroviral therapy is stopped HBV can become reactivated. This case is unique in it's presentation of seizures in the setting of acute reactivation of HBV, timely initiation of antiviral treatment in acute hepatitis with successful recovery despite poor prognosis, and management options for acute liver failure at a tertiary medical center.Figure: Prevalence of Chronic Hepatitis B Virus Among HIV Figure: Understanding Hepatitis B Serology"

CNS Disorders • Epilepsy • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Liver Failure • CD4

When the Therapy Bites Back: Drug-Induced Necrotizing Pancreatitis in an HIV Positive Patient (ACG 2025) - "Two months prior to admission, the patient's antiretroviral therapy had been switched from dolutegravir/lamivudine to DRV/COBI/FTC/TAF due to weight gain. Drug-induced pancreatitis was determined to be the cause of severe necrotizing pancreatitis in our patient after other causes were ruled out. As novel antiretroviral therapies emerge, HIV positive patients should be closely monitored for rare complications following initiation or modification of therapy."

Clinical • CNS Disorders • Dyslipidemia • Gastroenterology • Hepatology • Human Immunodeficiency Virus • Hypertriglyceridemia • Infectious Disease • Pancreatitis • Septic Shock

TYPE B AORTIC DISSECTION COMPLICATED BY ESCHERICHIA COLI-INDUCED AORTITIS (CHEST 2025) - "CASE PRESENTATION: A 53-year-old woman with HIV on darunavir/cobicistat/emtricitabine/tenofovir alafenamide presented with chest pain radiating to her back and severe left flank pain...The patient was initially started on ceftriaxone for a suspected urinary tract infection (UTI) and transferred to our facility. Previously acquired blood and urine cultures grew E. coli, leading to escalation to cefepime. Despite initial treatment, including antibiotics and tight blood pressure control with IV clevidipine and esmolol, persistent fevers and leukocytosis prompted further investigation.Subsequent CT imaging revealed new inflammatory changes around the false lumen of the infrarenal aorta, raising concern for E. coli-associated aortitis...After stabilization, she was discharged a six-week oral course of cefdinir due to social barriers preventing home IV antibiotic therapy... This case highlights the importance of recognizing rare infectious complications of aortic dissections...."

Atherosclerosis • Cardiovascular • Chronic Obstructive Pulmonary Disease • Diabetes • Human Immunodeficiency Virus • Hypertension • Immunology • Infectious Disease • Metabolic Disorders • Nephrology • Respiratory Diseases

THE FIRE WITHIN: PARADOXICAL PULMONARY INFLAMMATION UNMASKED BY IMMUNE RECONSTITUTION (CHEST 2025) - "He was started on a fixed-dose combination therapy of cobicistat, darunavir, emtricitabine, and tenofovir alafenamide (Symtuza) alongside doxycycline for syphilis.Despite adherence to ART, the patient developed progressive fatigue, subjective fevers, dry cough, and worsening malaise, leading to hospital admission...Prednisone therapy was initiated, resulting in marked clinical improvement within 48 hours... Recognition, timely initiation of corticosteroid therapy, and coordinated multidisciplinary management crucial for improving outcomes in patients with IRIS. Early involving of infectious disease specialists and pulmonary consultation is essential to differentiate IRIS from progressive infections and to optimize management strategies. This case highlights the need for clinicians to remain vigilant for pulmonary IRIS in patients with advanced HIV starting ART, as early intervention can significantly improve prognosis."

Cough • Fatigue • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Pneumonia • Tuberculosis • CD4

Interaction between GLP-1 receptor agonists and cART in PLWH and obesity: a case report (EACS 2025) - "Newer regimens, particularly those containing second-generation integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF), have been associated with significant weight gain, while tenofovir disoproxil fumarate (TDF) appears to have a weight-suppressive effect.We describe a 62-year-old man living with HIV on a stable ART regimen (TAF/FTC/DRV/c), with a history of hypertensive heart disease and class II obesity (BMI 35 kg/m2). This case highlights the potential of GLP-1 receptor agonists as an effective treatment option for obesity in PLWH, particularly when lifestyle modifications have failed. Further studies are warranted to explore their long-term safety and efficacy in this population, and to better characterize any pharmacological interactions with antiretroviral therapy."

Case report • Clinical • Human Immunodeficiency Virus • Infectious Disease

Virological failure with NNRTI resistance on CAB+RPV-LA in a man with subtherapeutic cabotegravir levels (EACS 2025) - "He achieved sustained virological suppression (HIV-RNA 10 years on oral ART (TDF/FTC/EFV, then TDF/3TC/DOR)...Oral TAF/FTC/DRV/c was briefly initiated but stopped once the subsequent HIV-RNA measurement was <50 c/mL and HIV-DNA sequencing showed no RAMs... This case suggests a potential influence of injection technique and illustrates how retrospective TDM can help elucidate pharmacological contributors to virological failure on long-acting injectables. TDM may assist clinical decision-making in selected cases and inform real-world optimisation strategies."

Human Immunodeficiency Virus • Infectious Disease • CD4

Possible CNS compartmentalization and lenacapavir resistance in multidrug-resistant HIV (EACS 2025) - "Due to resistance to four antiretroviral classes, a salvage regimen was initiated in August 2023 including darunavir/cobicistat/emtricitabine/tenofovir alafenamide, fostemsavir, and subcutaneous lenacapavir every six months, according to CAPELLA study criteria*. 2022;386(19):1793-1803. doi:10.1056/NEJMoa2115542."

Human Immunodeficiency Virus • Infectious Disease • CD4

Intersecting Pathologies: A Unique Case of Usual Interstitial Pneumonia and Organizing Pneumonia in an HIV Patient (ATS 2025) - "Clinical summary: A 65-year-old male with a past medical history of coronary artery disease and HIV on darunavir/ cobicistat/ emtricitabine /tenofovir alafenamide (CD4 - 667, viral load - 30) presented with fever, flu-like illness, and shortness of breath for 4 days, with no sick contacts and noncontributory social history...Intravenous Levofloxacin was commenced for possible bilateral atypical pneumonia; however, throat, sputum, and blood culture showed no growth... Non-infectious lung complications are rare but challenging to manage in HIV patients. The coexistence of usual interstitial pneumonia (UIP) and organizing pneumonia (OP) suggests a complex underlying process. This inflammatory and fibrotic response can worsen symptoms and lead to disease progression."

Clinical • Acute Lung Injury • Cardiovascular • Coronary Artery Disease • Fibrosis • Human Immunodeficiency Virus • Immunology • Infectious Disease • Interstitial Lung Disease • Pneumonia • Pulmonary Arterial Hypertension • Respiratory Diseases • CD4

Cabotegravir/rilpivirine resistance in a patient living with HIV despite on-time administration: A case report. (PubMed, Am J Health Syst Pharm) - "This case demonstrates the potential for patients living with HIV to develop resistance to CAB/RPV despite on-time administration of the medication. Proper administration and timing of antiretroviral therapy for these patients is essential to ensure efficacy and safety in the management of HIV but does not completely prevent development of resistance."

Journal • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease

An Investigation of Granulomatous Liver Injury in Immunocompetent and Immunocompromised Patients at a Tertiary Care Center (USCAP 2025) - "Implicated drugs included ipiliumumab, etanercept, Symtuza, and others. In our large case series, the etiology of granulomatous liver injury was determined in a majority of patients, while 31% of cases were unknown. Immunosuppressed patients had a higher proportion of granulomas attributed to steatosis, infection, and rejection in comparison to immunocompetent patients. A retrospective investigation of the 77 idiopathic cases is ongoing to determine whether H+E re-review and further clinicopathologic correlation is revealing."

Clinical • Autoimmune Hepatitis • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Hepatitis B • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Failure • Nontuberculous Mycobacterial Disease • Respiratory Diseases • Rheumatology • Sarcoidosis

Rapid start with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) as initial treatment in people with HIV‐1 (PWH): a systematic literature review (SLR) of clinical and patient‐reported outcomes (PROs) (HIV-Glasgow 2024) - "Efficacy and safety outcomes at key timepoints reported by included rapid start (RS) studies Characteristic/Endpoints BIC-NOW (Spain) [5] BIFAST (Spain) [6] FAST (France) [7] Rainbow (Italy) [8] Test&Treat (Spain) [9] Benidir 2022 (USA) [10] Study design Single arm Single arm Single arm Single arm Single arm Non-RCT (RS vs non-RS) Phase IV IV IV IV III NR Treatment arms B/F/TAF RS (n=208) B/F/TAF RS (n=59) B/F/TAF RS (n=112) B/F/TAF RS (n=30) B/F/TAF RS (n=100) B/F/TAF RS (n=65) B/F/TAF non-RS (n=42) Efficacy Outcomes Virologic suppression (Viral load <50 copies/mL) W24 (n=160), 88.8% W24 (n=59), 84.4% W24 (n=112), 80.4% W24 (n=30), 80%, p < 0.001 W4 (n=100), 52% Visit 5 (timepoint NR) (n=65), 100%, p ≥ 0.05 Visit 5 (timepoint NR) (n=42), 100% Engagement in care (Attendance at visits) W48 (n=30), 100% W4 (n=100), 100% Visit 4 (median 192.0 [IQR 185.0,238.0] days) (n = 16), 56.3%, p = 0.003 Visit 4 (median 243.5 [IQR 180.2, 306.8] days) (n = 22), 9.1% Safety..."

Clinical • Patient reported outcomes • Review • CNS Disorders • Depression • Human Immunodeficiency Virus • Infectious Disease • Mood Disorders • Psychiatry

Comparison of treatment‐emergent resistance associated mutations among single tablet regimens and cabotegravir+rilpivirine for the treatment of virologically suppressed people with HIV: a systematic literature review and network meta‐analysis (HIV-Glasgow 2024) - "Pooled estimates for risk of TE-RAMs at 48 weeks (RR [95% CI]) B/F/TAF 0.45 (0.05−4.34) CAB+RPV Q4W 0.20 (0.02−1.83) 0.44 (0.16−1.22) CAB+RPV Q8W 0.34 (0.00−30.94) 0.76 (0.01−79.65) 1.74 (0.02−186.99) D/C/F/TAF 0.99 (0.02−49.69) 2.21 (0.02−205.13) 5.04 (0.06−458.15) 2.90 (0.01−1134.89) DTG+2NRTIs 0.35 (0.01−12.32) 0.78 (0.02−28.74) 1.78 (0.05−69.14) 1.03 (0.01−163.78) 0.35 (0.00−70.41) DTG/3TC 1.00 (0.02−50.04) 2.23 (0.02−206.57) 5.08 (0.06−461.38) 2.92 (0.01−1142.90) 1.01 (0.00−256.15) 2.85 (0.01−566.10) DTG/ABC/3TC 0.35 (0.00−31.65) 0.79 (0.01−81.51) 1.80 (0.02−191.35) 1.04 (0.00−261.33) 0.36 (0.00−138.70) 1.01 (0.01−159.53) 0.35 (0.00−137.72) DTG/RPV 0.26 (0.03−2.01) 0.58 (0.08−4.41) 1.31 (0.15−11.17) 0.75 (0.01−54.12) 0.26 (0.00−21.66) 0.73 (0.04−14.89) 0.26 (0.00−21.51) 0.73 (0.01−51.62) E/C/F/TXF 0.10 (0.01−1.81) 0.22 (0.01−4.52) 0.49 (0.02−10.90) 0.28 (0.00−26.61) 0.10 (0.00−12.98) 0.28 (0.01−5.57) 0.10 (0.00−12.89) 0.27 (0.00−25.40) 0.37 (0.04−3.95) EFV/FTC/TDF..."

Retrospective data • Review • Human Immunodeficiency Virus • Infectious Disease

The Late Presenter Treatment Optimisation Study (clinicaltrials.gov) - P3 | N=447 | Completed | Sponsor: NEAT ID Foundation | Active, not recruiting ➔ Completed

Metastases • Trial completion • Human Immunodeficiency Virus • Infectious Disease • CD4

A randomised control trial of BIC/F/TAF vs DRV/c/F/TAF in context of HIV test-and-treat, BicTnT. (PubMed, HIV Res Clin Pract) - "Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. Both regimens demonstrated good tolerability with infrequent laboratory abnormalities and no grade 3 or 4 adverse events. In this first head-to-head study in the context of ART initiation, HIV RNA decline from baseline to week 12 was significantly more rapid for BIC/F/TAF compared with DRV/c/F/TAF."

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

DEFINE: A Prospective, Randomized, Phase 4 Trial to Assess a Protease Inhibitor-based Regimen Switch Strategy to Manage Integrase Inhibitor-related Weight Gain. (PubMed, Clin Infect Dis) - P4 | "While no significant change in body weight was observed at 24 weeks after switching from InSTI+TAF/FTC to D/C/F/TAF among adults with weight gain, a trend towards weight loss emerged with longer time post-ARV switch, supporting further investigation of antiretroviral selection/switch for weight management."

Journal • P4 data • Human Immunodeficiency Virus • Infectious Disease

First Case of HIV Seroconversion With Integrase Resistance Mutations on Long-Acting Cabotegravir for Prevention in Routine Care. (PubMed, Open Forum Infect Dis) - "Viral suppression was maintained for 6 months on darunavir/cobicistat/emtricitabine/tenofovir alafenamide, then switched to doravirine + emtricitabine/tenofovir alafenamide due to nausea. Accelerated pathways to minimize time between HIV testing and CAB-LA initiation are needed to optimize acute HIV detection and mitigate resistance risk. Sustained product access regardless of insurance is imperative to reduce HIV infections on CAB-LA."

Journal • Human Immunodeficiency Virus • Infectious Disease

Characteristics and outcomes of Virally Suppressed (VS) Treatment Experienced (VSTE) people with HIV (PWH) (AIDS 2024) - "Of PWH with results within 3 years, 78% had =1 major mutation (48% NRTIs, 44% NNRTIs, 26% PIs, 11% INSTIs); 44% =2 class resistance; most common mutations: M184VI (34%); A62V (33%); K103NS (22%).During follow-up (median 2.8 years), 5% had =1 VB and 6% had VF (more common on regimens >2 core classes, 9% vs 5% p2 Core ARV Classes1,082 (19%)243 (22%)74 (30%)93 (9%)VSTE: virologically suppressed treatment experienced; ARV: antiretroviral; HTE: heavily treatment experienced; STR: single tablet regimen; Core regimen classes: non-nucleoside reverse transcriptase inhibitors [NNRTIs], integrase inhibitors [INSTIs], nucleoside/nucleotide reverse transcriptase inhibitors [NRTIs], protease inhibitors [PIs].†Complex regimen: 2 out of 3 core classes (NNRTI, PI, INSTI), darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) or tenofovir disoproxil fumarate (TDF), multi-dosing per day, complex multi-pill regimen (excluding regimens reflecting available single-tablet..."

Human Immunodeficiency Virus • Infectious Disease

Additional time post–integrase inhibitor to protease inhibitor switch shows trend to weight loss: DEFINE 48-week results (AIDS 2024) - P4 | "The primary analysis of DEFINE found no significant difference in percent body weight change from baseline to Week 24 when switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) vs continuing INI+TAF/emtricitabine (FTC)... The trajectory of weight change after INI to PI switch appeared different in the first 24 weeks post-switch (no weight loss observed) vs Weeks 24-48, where a trend to weight loss emerged. Secondary metabolic endpoints remained stable or paralleled weight loss. Longer time post–ARV switch suggests medication management may be an important component to address this issue."

Human Immunodeficiency Virus • Infectious Disease

A RARE CASE OF VANISHING BILE DUCT SYNDROME IN A PATIENT WITH ADVANCED HIV/AIDS AND CMV HEPATITIS (DDW 2024) - "His home medications included darunavir cobicistat emtricitabine and tenofovir alafenamide...Medications that are commonly implicated include penicillin and nevirapine...There is limited data on treatment options for VBDS; oftentimes it is removal of the offending medication or treating the underlying infection and malignancy. In many cases of VBDS ductopenia can become permanent leading to progressive cholestasis and ultimately cirrhosis."

Clinical • Metastases • Autoimmune Hepatitis • Cholestasis • Cytomegalovirus Infection • Fibrosis • Graft versus Host Disease • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Oncology • Transplant Rejection • Transplantation • CD4

Severe Hyperglycemia After Initiation Of Bictegravir Antiretroviral Therapy With Resolution Upon Discontinuation (ENDO 2024) - "Her initial ART was darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Due to intolerable GI side effects, six years later, she was switched to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)...Her HIV regimen was switched to FTC/TAF and doravirine due to suspicion of BIC-induced hyperglycemia...Two years later on metformin and linagliptin: HbA1c was 6.1% and beta-cell function did not reveal insulin deficiency or resistance (non-fasting blood glucose 96 mg/dL, insulin 13.5 uIU/mL [RR 2.6-24.9 mIU/mL], C-peptide 3.7 ng/mL [RR 1.1-4.4 ng/mL])... Patients with HIV and a history of obesity and/or dysglycemia who are switched to a BIC-containing ART regimen should be educated and monitored for acute hyperglycemia. This may be due to impaired beta-cell function and/or insulin resistance; however, further research is needed to understand the mechanism. An alternative ART regimen should be considered if hyperglycemia develops."

Late-breaking abstract • Diabetes • Genetic Disorders • Gestational Diabetes • Human Immunodeficiency Virus • Hypoglycemia • Immunology • Infectious Disease • Metabolic Disorders • Obesity • CD4

Assessment of swallowability and acceptability of scored darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) tablets in HIV-1-infected children aged ≥6 to <12 years, using matching placebo tablets: A randomized study. (PubMed, Antivir Ther) - P1 | "Scored D/C/F/TAF FDC tablets are swallowable - with whole favoured over split - and considered at least acceptable for long-term daily intake in children living with HIV-1 aged ≥6 to <12 years."

Clinical • Journal • P1 data • Human Immunodeficiency Virus • Infectious Disease

Rapid Reinitiation of a Single Tablet Antiretroviral Therapy Using Symtuza® in HIV-1 Infected Treatment-Experienced Patients Off Therapy. (ReSTART) (clinicaltrials.gov) - P4 | N=75 | Completed | Sponsor: The Crofoot Research Center, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ Apr 2024 | Trial primary completion date: Sep 2023 ➔ Apr 2024

Trial completion • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Phase 4 DEFINE Switch Study to Manage InSTI-related Weight Gain: Metabolics and Biomarker Analysis (CROI 2024) - P4 | "As previously reported, the primary Week 24 analysis found no significant difference in percent change in body weight from baseline when switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) compared to continuing INSTI+tenofovir alafenamide (TAF)/emtricitabine (FTC).DEFINE (NCT04442737) is a randomized (1:1), prospective, 48-week, active-controlled, open-label, multicenter phase 4 study evaluating switching to D/C/F/TAF versus continuing INSTI+TAF/FTC in virologically suppressed adults with HIV-1 who had ≥10% weight gain while on the INSTI-based regimen...Consistent with the minimal body weight changes observed through Week 24, metabolic and biomarker data remained relatively stable. Metabolic parameters in this high-BMI population did not improve following antiretroviral switch, highlighting that weight gain should be a pretreatment consideration."

Biomarker • P4 data • Fibrosis • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • LEP