CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

Results: A total of 61 PWH (57% male; age 56 (43-60) years old) were enrolled. All were receiving LEN as an add-on to their antiretroviral regimen. Among them, 28 received both CAB long-acting intramuscular injection q8w with an associated daily oral antiretroviral backbone. A total of 191 LEN Cpl were measured in these PWH. Over all PWH, median (IQR) LEN Cpl were 50 (28-74) ng/mL with a number of samples per PWH of 2 (1-5). The intra-individual coefficient of variation was 30%, while the inter-individual variability was 69%. LEN Cpl were 44 (15-95) ng/mL, 28 (23-67) ng/mL, 45 (27-63) and 47 (29-73) ng/mL at W2, M1, M6, M6 and M12, respectively. Among our PWH, only one presented a LEN Cpl below the cutoff of 15 ng/mL. Of note, 5 patients presented LEN Cpl above 150 ng/mL, corresponding to PWH with acute or chronic kidney disease and/or receiving ritonavir-boosted atazanavir containing regimens. To date, no specific adverse events have been reported in these PWH, except some injection site reactions. Conclusions: In our population of HTE HIV patients, PWH had adequate LEN Cpl. No drug-drug interaction was reported and tolerance of antiretroviral multitherapy was acceptable.

mg. P:T ratios support an extended intracellular half-life of FRTP compared to the parent form, in line with prior in vitro studies. Correlation between plasma FVP and FRTP was better using HC compared to PBMC indicating that dried filter spots may be more robust than PBMC for the purpose of intracellular FRTP quantitation and offer a pragmatic alternative to venepuncture in field settings.

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658

Integrase Inhibitor- Versus Protease Inhibitor-Based Therapy for People With Advanced HIV-Disease Georg M. N. Behrens 1 , Lambert Assoumou 2 , Geoffroy Liegeon 3 , Andrea Antinori 4 , Rafael Mican 5 , Stephane De Wit 6 , Frank Post 7 , Juergen K. Rockstroh 8 , Lisa Hamzah 9 , Pere Domingo 10 , Adrian Curran 11 , Montserrat Laguno 12 , Carl Fletcher 13 , Jack Moody 13 , Anton Pozniak 13 , for the LAPTOP Study Team 1 Hannover Medical School, Hannover, Germany, 2 Assistance Publique – Hôpitaux de Paris, Paris, France, 3 Université Paris Cité, Paris, France, 4 National Institute for Infectious Diseases L Spallanzani, Rome, Italy, 5 Hospital La Paz Institute for Health Research, Madrid, Spain, 6 Saint-Pierre University Hospital, Brussels, Belgium, 7 King's College Hospital NHS Foundation Trust, London, UK, 8 Bonn University Hospital, Bonn, Germany, 9 St George's University Hospitals NHS Foundation Trust, London, UK, 10 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 11 Hospital Universitari Vall d'Hebron, Barcelona, Spain, 12 Hospital Clinic of Barcelona, Barcelona, Spain, 13 Chelsea and Westminster Hospital, London, UK Background: To date clinical trials have been underpowered to assess the preferred antiretrovirals in therapy-naïve people with advanced HIV disease (PWAH). We investigated the efficacy and safety of an integrase inhibitor (INI) versus a boosted protease inhibitor (PI) containing regimen in PWAH. Methods: In this open-label, randomised, multicentre, non-inferiority trial, therapy-naive people with HIV aged ≥18 years, a viral load >1000 copies/mL, and either AIDS at any CD4 cell count, severe bacterial infection (BI) with a CD4 cell count <200/µL, a CD4 cell count <100/µL, or currently being treated for opportunistic infections (OI), were randomised 1:1 to receive bictegravir or darunavir/cobicistat, each co-formulated with tenofovir alafenamide/ emtricitabine for 48 weeks. The time to first occurrence of the primary outcome, which was a composite of specified virological failure (insufficient virological response was defined as HIV-1 RNA reduction <1 log 10 copies/mL at week 12, or viral load >50 HIV-1 RNA copies/mL at week 48) or clinical events plus the individual components were evaluated by Kaplan Meier and Cox regression analyses, with a non-inferiority margin of 1.606 in the hazard ratio. Results: 442 participants were randomised and well matched for baseline characteristics with a median age of 43 years, 81% male, and 62% white. 85.8% had CD4 T cell counts <100/µL and 44.6% viral loads >500,000 HIV-1 RNA copies/mL. In intention-to-treat analyses, the primary composite outcome event occurred in 49/220 patients in the INI group versus 70/222 patients in the PI group by 48 weeks (adjusted hazard ratio [aHR] 0.70; 95% confidence interval [CI] 0.48-1.00; p=0.05, noninferiority demonstrated). The per-protocol analysis gave a similar estimated aHR of 0.69 (95% CI 0.48-1.00). Kaplan-Meier estimates for virological failure was significantly lower in the INI versus PI group (aHR 0.54; 95% CI 0.33-0.88, p=0.013); however, clinical events were similar between groups (Figure 1). Incidence of drug-related AE (grade ≥2) was 13.7 in the INI group versus 21.7 per 100 person-years in the PI group (p=0.04). The incidence of grade 3-4 drug-related AEs (p=0.99), AE leading to study drugs interruption (p=0.92), and serious AEs (p=0.82) did not differ between groups. Conclusions: In PWAH the bictegravir containing regimen was non-inferior to the darunavir containing regimen in terms of the composite outcome but had a better virologic response at week 48 and fewer overall AE.

Poster Abstracts

657

Intracellular Pharmacokinetics of Favipiravir-5’-Ribofuranosyl Triphosphate in People With COVID-19 Elizabeth Challenger 1 , Laura J. Else 1 , Laura Dickinson 1 , Tim Rowland 2 , Colin Hale 3 , Rebecca Lyon 3 , Helen E. Reynolds 1 , Justin Chiong 1 , Beth Thompson 1 , Richard Fitzgerald 3 , Henry Pertinez 1 , Andrew Owen 1 , Tom E. Fletcher 2 , Saye Khoo 1 , for the AGILE CST-6 Study Group 1 University of Liverpool, Liverpool, UK, 2 Liverpool School of Tropical Medicine, Liverpool, UK, 3 Royal Liverpool University Hospital, Liverpool, UK Background: Favipiravir (FVP) is an anti-influenza agent but preclinical data support broad spectrum antiviral activity against RNA viruses including SARS-CoV-2 and haemorrhagic fevers. Pharmacokinetic (PK) data on the active form, favipiravir ribofuranosyl-5’-triphosphate (FRTP), are lacking in humans. We measured liquid plasma (LPL) FVP and intracellular FRTP measurements in PBMC and compared this with HemaSep filter cards that separate cells (HC) and plasma (HPL) upon contact. Methods: AGILE CST-6 (NCT04746183) is a phase Ib dose escalation study to evaluate intravenous FVP for treatment of COVID-19. Patients (n=6/cohort) with SARS-CoV-2 were randomised 2:1 to receive FVP (600 mg, 1200mg, 1800mg, 2400 mg BD) or standard of care. LPL and HemaSep were collected on Day (d) 1, 3 and 5 over 0-12 hours post-completion of infusion and PBMC at 6-12 hours. FVP was quantified in LPL and HPL, and FRTP from HC and PBMC using validated LC-MS/MS methods. FRTP concentrations were expressed as pmol/ sample (12mm punch, HC) and pmol/10 6 cells (PBMC). PK parameters were calculated using WinNonlin. Results: 16 patients [7 female at birth; median (range) age, weight: 77 years (52-93), 79kg (52-125)] were enrolled. Analysis included 153 HemaSep|38 PBMC, of which 47 (31%)|25 (66%) had quantifiable FRTP. In PBMC, there was high interindividual variability and limited evidence for accumulation of FRTP from d1-d5, confounded by sampling issues (26% haemolysed). PBMC FRTP ranged from 20.8-141.4 pmol/10 6 cells. In HC, all d1 samples were

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