Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) / Gilead - LARVOL DELTA

Prevention and Treatment Continuum for Youth at HIV Risk, Acutely Infected and With Established HIV Infection (clinicaltrials.gov) - P=N/A | N=101 | Completed | Sponsor: University of California, Los Angeles | Active, not recruiting ➔ Completed | N=72 ➔ 101

Enrollment change • Trial completion • Human Immunodeficiency Virus • Infectious Disease

Efficacy of Switching to Ainuovirine-Based Antiretroviral Regimen in Virologically Suppressed PWH (CROI 2025) - "Background In the SPRINT study, switch to ainuovirine, a novel non-nucleoside reverse transcriptase inhibitor, combined with lamivudine and tenofovir DF (ANV/3TC/TDF), was non-inferior to that to cobicistat-boosted elvitegravir with emtricitabine and tenofovir alafenamide (E/C/F/TAF) for virologically suppressed (VS) people with HIV-1 (PWH) in 48-week virologic efficacy endpoint. Conclusions VS was well preserved in PWH with second- or third-line switch to ANV/3TC/TDF through 96 weeks. Immunologic outcomes might favor a "same-class" switch to ainuovirine-based regimen, and warranted further investigation into the changes in the viral reservoir and immune functionality of VS PWH switching antiretroviral regimen."

Clinical • Human Immunodeficiency Virus • Infectious Disease • CD4

Pharmacokinetics, safety and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in children with HIV aged from 2 years and weighing at least 14 kg. (PubMed, J Int AIDS Soc) - P2/3 | "These data support the use of single-tablet E/C/F/TAF (90/90/120/6 mg) regimen for the treatment of HIV in children aged ≥2 years and weighing ≥14-<25 kg."

Journal • PK/PD data • Human Immunodeficiency Virus • Infectious Disease • Pediatrics • Pneumonia • Respiratory Diseases • CD4

Signal detection and analysis of adverse events associated with Genvoya® based the FAERS database. (PubMed, Front Pharmacol) - "Clinicians should closely monitor these reactions and implement necessary preventive and intervention measures based on patient-specific conditions and treatment guidelines. Although this study has limitations, the analysis of FAERS database data has revealed various potential risks associated with Genvoya®, providing important safety references for HIV treatment."

Adverse events • Journal • CNS Disorders • Cognitive Disorders • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease

B-free Multistage Trial (clinicaltrials.gov) - P4 | N=210 | Enrolling by invitation | Sponsor: Insel Gruppe AG, University Hospital Bern | Trial completion date: Dec 2027 ➔ Sep 2027 | Trial primary completion date: Nov 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

The clinical utility of targeted screening for liver fibrosis/cirrhosis among people living with HIV (PLWH) (HIV-Glasgow 2024) - "The antiretroviral combination of TAF and INI (excluding Genvoya) had statistically significant association with ≥S1 steatosis (OR 3.4)... Our data show a low prevalence of liver cirrhosis. Routine FibroScan may not be cost effective in diagnosing cirrhosis in PLWH with a single liver risk factor; however, prevalence increases in the presence of multiple risk factors. We recommend fibrosis-4 index (FIB-4) score as an inexpensive primary screening tool for fibrosis/cirrhosis, and FibroScan for those with multiple risk factors or high FIB-4 score."

Clinical • Fibrosis • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatotic Liver Disease • CD4

Favourable cholesterol profile in virologically suppressed people with HIV‐1 switching to tenofovir DF‐ containing, ainuovirine‐based compared to tenofovir alafenamide‐containing, boosted elvitegravir‐ based antiretroviral regimen: normocholesterolemic subgroup analyses of the SPRINT trial, a randomised, active‐controlled phase III study (HIV-Glasgow 2024) - "Background: In the SPRINT trial, virologically suppressed people with HIV-1 (PWHs) switched to tenofovir DF (TDF) containing, ainuovirine (ANV, ACC008) based or tenofovir alafenamide (TAF) containing, boosted elvitegravir (EVG/c) based antiretroviral (ARV) regimen (comparator) from an efavirenz-based regimen. In PWHs with baseline normocholesterolaemia, switching to a TDF-containing, ANV-based regimen resulted in less LDL-C increase and better lipidaemic control compared to a TAF-containing, EVG/c-based regimen."

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

Virological suppression, viral blip, low‐level viraemia, and confirmed viraemia in virologically suppressed people with HIV‐1 switching to tenofovir DF‐containing, ainuovirine‐based antiretroviral regimen: secondary, and subgroup virological efficacy analyses of the SPRINT trial, a randomized, active‐ controlled phase III study (HIV-Glasgow 2024) - "ANV/3TC/TDF, ainuovirine/lamivudine/tenofovir disoproxil; E/C/F/TAF, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. High proportion of virological suppression was achieved in virologically suppressed PWHs switching to ANV/3TC/TDF non-inferior to EVG/c/FTC/TAF. Viral blip, LLV, and confirmed viraemia occasionally occurred, which normally did not require alteration of ART regimen."

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease

SARS‐CoV‐2 vaccination and coronaviral disease 2019 in virologically suppressed people with HIV‐1 previously on NNRTI‐based antiretroviral regimen during the pandemic: the secondary longitudinal analysis of the SPRINT study, a multi‐centre, randomised, active‐controlled phase III trial (HIV-Glasgow 2024) - "This study compared efficacy and safety of switch to ainuovirine plus lamivudine and tenofovir DF (ANV/3TC/TDF) and that to cobicistat-boosted elvitegravir plus emtricitabine and tenofovir alafenamide (E/C/F/TAF) in virologically suppressed PWH previously on NNRTI-based antiretroviral (ARV) regimen. The SPRINT study population, a representative subset of virologically suppressed PWH, was well vaccinated against SARS-CoV-2 during the pandemic. No severe or critical illness of COVID-19 occurred in this subpopulation, at a low incidence of testing positivity, and established or suspected diagnosis."

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

Improved uric acid metabolism in virologically suppressed people with HIV‐1 switching to tenofovir DF‐ containing, ainuovirine‐based compared to tenofovir alafenamide‐containing, boosted elvitegravir‐ based antiretroviral regimen: the secondary analyses of 48‐week results of the SPRINT trial, a randomised, active‐controlled phase III study (HIV-Glasgow 2024) - "ANV/3TC/TDF, ainuovirine/lamivudine/tenofovir disoproxil; E/C/F/TAF, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Switching to tenofovir DF-containing, ANV-based regimen resulted in constant glucose but improved uric acid metabolism in virologically suppressed PWHs compared to that to TAF-containing, boosted EVG-based regimen. Glucose or uric acid dysmetabolism should be well addressed although diabetes or gout occasionally emerges in virologically suppressed PWHs."

Clinical • P3 data • Diabetes • Gout • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammatory Arthritis • Metabolic Disorders • Rheumatology

Immunological efficacy and early response in virologically suppressed people with HIV‐1 switching to tenofovir DF‐containing, ainuovirine‐based compared to tenofovir alafenamide‐containing, boosted elvitegravir‐based antiretroviral regimen: secondary immunological efficacy analyses of the SPRINT trial, a randomized, active‐controlled phase III study (HIV-Glasgow 2024) - "ANV/3TC/TDF, ainuovirine/lamivudine/tenofovir disoproxil; E/C/F/TAF, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. Immunological efficacy was comparable between virologically suppressed PWHs, switching to ANV/3TC/TDF and those to EVG/c/FTC/TAF, few of whom were severely immunocompromised at baseline. However, switch to ANV/3TC/TDF resulted in a favourable early immunological response within the first 12 weeks of switch, compared to that to EVG/c/FTC/TAF."

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Prevalence of integrase strand transfer inhibitor resistance in people living with HIV and virological failure. (PubMed, J Chin Med Assoc) - "INSTI resistance was uncommon when used as the first-line single tablet regimen in Taiwan. The results confirmed the robustness of ABC/DTG/3TC and BIC/FTC/TAF regarding integrase resistance in cases of virological failure in routine clinical care."

Journal • Human Immunodeficiency Virus • Infectious Disease

Effectiveness, safety, and patient-reported outcomes of emtricitabine/tenofovir alafenamide-based regimens for the treatment of HIV-1 infection: Final 24-month results from the prospective German TAFNES cohort study. (PubMed, HIV Med) - "Real-world data confirmed a favorable safety profile and high virologic effectiveness with high treatment satisfaction on F/TAF-based ART."

Journal • Patient reported outcomes • Chronic Kidney Disease • Human Immunodeficiency Virus • Infectious Disease • Nephrology • Renal Disease • CD4

Clinical efficacy and safety of new compound single tablet antiviral drugs in the treatment of HIV/AIDS. (PubMed, Life Sci) - "Genvoya, Biktarvy and Dovato are recommended for the treatment of HIV/AIDS and have a good safety profile."

Journal • Dyslipidemia • Human Immunodeficiency Virus • Infectious Disease • CD4 • CRP

Study to Evaluate the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents and Virologically Suppressed Children (clinicaltrials.gov) - P2/3 | N=129 | Active, not recruiting | Sponsor: Gilead Sciences | Trial completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Human Immunodeficiency Virus • Infectious Disease

Bictegravir/emtricitabine/tenofovir alafenamide in adults with HIV-1 and end-stage kidney disease on chronic haemodialysis. (PubMed, HIV Med) - P3b | "These findings support the use of the once-daily B/F/TAF single-tablet regimen for people with HIV-1 and ESKD on HD. This regimen offers a convenient treatment option for this population as it reduces the need for dose adjustment, eases pill burden and avoids potential drug-drug interactions associated with alternatives that may impact individuals on multiple medications or awaiting transplantation."

Journal • Chronic Kidney Disease • Human Immunodeficiency Virus • Infectious Disease • Nephrology • Renal Disease • Transplantation

A Study to Provide Continued Access to Study Drug to Children and Adolescents Who Have Completed Clinical Studies Involving Gilead HIV Treatments (clinicaltrials.gov) - P4 | N=350 | Recruiting | Sponsor: Gilead Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Switch to fixed-dose ainuovirine, lamivudine, and tenofovir DF versus elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV-1: the 48-week results of the SPRINT trial, a multi-centre, randomised, double-blind, active-controlled, phase 3, non-inferiority trial. (PubMed, Lancet Reg Health West Pac) - "We compared the efficacy and safety profiles of ainuovirine (ANV), a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), with boosted elvitegravir (EVG), both coformulated with two nucleoside reverse transcriptase inhibitors (NRTIs), in people living with HIV-1 (PLWH) who had achieved virological suppression on previous NNRTI-based antiretroviral (ARV) regimen. In virologically suppressed PLWH on previous NNRTI-based ARV regimen, switch to ANV/3TC/TDF resulted in less weight gain, and improved lipid metabolism while maintaining virological suppression non-inferior to that to EVG/Cobi/FTC/TAF. Jiangsu Aidea Pharmaceutical & the National "Thirteenth Five-year Period" Major Innovative Drugs Research and Development Key Project of the People's Republic of China Ministry of Science and Technology."

Head-to-Head • Journal • P3 data • Dyslipidemia • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders

Noninferior efficacy, reduced weight gain, and improved lipid metabolism of switch to ainuovirine- versus boosted elvitegravir-based regimen in virologically suppressed people living with HIV-1: 48-week results of the SPRINT trial???? (AIDS 2024) - "Participants were randomly assigned to receive ANV 150 mg, lamivudine (3TC) 300 mg and tenofovir disoproxil fumarate (TDF) 300 mg or cobicistat (Cobi) 150 mg boosted EVG, emtricitabine (FTC) 200 mg and tenofovir alafenamide (TAF) 10 mg. In virologically suppressed PLWH, switch to ANV-based regimen resulted in less weight gain and improved lipid metabolism while maintaining virological suppression non-inferior to that to boosted EVG-based regimen."

Clinical • Dyslipidemia • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders

Spontaneous hip fracture in the background of HIV and Type 1 diabetes (AACE 2024) - "He was on Biktarvy (bictegravir + tenofovir alafenamide + emtricitabine) for 2 years. He previously took Genvoya (elvitegravir + cobicistat + alafenamide + emtricitabine)...Risk factors for AVN found in the HIV population include smoking, alcohol, megestrol acetate, antiphospholipid antibodies, use of glucocorticoids, hypercholesterolemia and hypertriglyceridemia... people living with HIV are at high risk for low bone density and fractures. It is important to remain vigilant in monitoring and optimizing risk factors that contribute to lower bone density and higher fracture risk in this population."

Diabetes • Dyslipidemia • Endocrine Disorders • Human Immunodeficiency Virus • Hypertriglyceridemia • Infectious Disease • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Pain • Type 1 Diabetes Mellitus • CD4

Bictegravir in the Elderly Living With HIV (BICEP) (clinicaltrials.gov) - P=N/A | N=162 | Active, not recruiting | Sponsor: State University of New York at Buffalo | Trial completion date: Jul 2023 ➔ Dec 2024 | Trial primary completion date: Jul 2023 ➔ Dec 2024

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

Genvoya-associated Iatrogenic Cushing's Syndrome (AACE 2024) - "The patient was switched from Genvoya to Biktarvy, triamcinolone injections were discontinued, and he was started on 10 mg of oral hydrocortisone in the morning, and 5 mg in the afternoon. Potent CYP450 inhibitors like cobicistat, a component of Genvoya, have been associated with the development of ICS and concomitant adrenal insufficiency by suppression of the HPA axis. Clinicians should be aware that co-administration of CYP450 inhibiting medications with exogenous corticosteroid, regardless of modality of exposure, can increase the likelihood of systemic adverse effects like ICS with adrenal insufficiency."

Cushing’s Disease • Diabetes • Endocrine Disorders • Human Immunodeficiency Virus • Infectious Disease • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Cytomegalovirus Colitis Causing Hemorrhagic Shock and Ileocolic Intussusception in a Patient With Acquired Immunodeficiency Syndrome (ATS 2024) - "The patient was started on broad-spectrum antibiotics, Genvoya and prophylaxis with atovaquone and azithromycin...Etoposide and dexamethasone were started for HLH...Blood transfusion with packed red blood cells, platelets and fresh frozen plasma was started and inotropic support with nor-epinephrine infusion was started...Ganciclovir was started for CMV colitis...Post-operatively, the patient improved remarkably and was discharged with itraconazole for disseminated histoplasmosis and valganciclovir for CMV colitis with outpatient clinic follow-up...The patient had a stormy course with multiple complications of disseminated histoplasmosis, HLH, and CMV Colitis, causing refractory lower gastrointestinal bleeding and ileocecal intussusception, for which the patient underwent right hemicolectomy. The multidisciplinary expert involvement and the timely intervention of the complications with rapid escalation to higher levels of care resulted in the successful outcome of the..."

Clinical • Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Human Immunodeficiency Virus • Immunology • Pain • Rare Diseases • Septic Shock • CD4

A Study to Provide Continued Access to Study Drug to Children and Adolescents Who Have Completed Clinical Studies Involving Gilead HIV Treatments (clinicaltrials.gov) - P4 | N=350 | Not yet recruiting | Sponsor: Gilead Sciences

New P4 trial • Human Immunodeficiency Virus • Infectious Disease • Pediatrics

Earlier Initiation of ART Reduces Intact Proviruses but Not Residual Viremia After 48 Weeks (CROI 2024) - "Wilcoxon rank-sum and Fisher's exact test were used for pairwise comparisons between Groups and Jonckheere-Terpstra test for trends across the 3 Groups.Participants had a median (IQR) age of 29 (24, 39) years, 11 (10%) were female, 3 (3%) identified as transgender, 58 (57%) were Black, and 103 (97%) initiated a regimen of EVG/COBI/FTC/TAF...Here we show that earlier ART lowers the levels of total and IPD in Groups 1 and 2 (Fiebig I-IV) compared with Group 3 (Fiebig V). Surprisingly, residual plasma HIV RNA was detected in >75% of participants at week 48 with no significant differences in proportions or levels between study Groups. These results provide new evidence that earlier ART does not affect the active HIV reservoir measured by plasma HIV RNA."

Human Immunodeficiency Virus • Infectious Disease • CD4