CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

659

Safety, Tolerability, and Efficacy of a BIC/FTC/TAF Dose Reduction Strategy Ivan Chivite 1 , Elisa De Lazzari 1 , Abiu Sempere 1 , Berta Torres 1 , Esther Fagundez 1 , Pilar Callau 1 , Sònia Vicens-Artés 2 , Cristina Rovira 1 , José Alcamí 1 , Maria Mar Mosquera-Gutierrez 1 , Amedeo De Nicolò 3 , Sonsoles Sánchez-Palomino 2 , Antonio D'Avolio 3 , Jose L. Blanco 1 , Esteban Martinez 1 , for the BETAF-RED Study Team 1 Hospital Clinic of Barcelona, Barcelona, Spain, 2 August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain, 3 University of Turin, Turin, Italy Background: The high potency and genetic barrier of BIC/TAF/FTC (BETAF), and the long-half lives of their components could allow for longer than once-daily dosing (OD) with low risk of developing resistance mutations. We assessed the feasibility of reducing BETAF OD to 3 (3W), 2 (2W), or 1 (1W) doses per week. Methods: Pilot randomized controlled trial (Clinicaltrials.gov NCT05602506). Consecutive PWH on BETAF OD ≥6 months with plasma HIV RNA (VL) <50 c/ mL, CD4 cells >350/µL, no resistance mutations to BETAF drugs, and no active hepatitis B or C were randomized (n=10 per arm) to: OD, 3W (Mon-Wed-Fri), 2W (Tue-Fri), or 1W (Wed) with visits at baseline, 4, 12, 24, 36, and 48 weeks. Primary endpoints were VL <50 c/mL (Snapshot ITT-exposed population) at 12 and 48 weeks. Individuals with viral failure (confirmed VL ≥50 c/mL) underwent genotypic resistance testing and were switched to OD up to 48 weeks. We measured ultrasensitive VL; total, defective and intact HIV reservoir (IPDA); CD4 and CD8 cells; hsCRP and IL-6; and plasma and intracellular trough drug levels at baseline, 12, and 48 weeks. The stopping rule was >30% viral failure in any of the dose reduction arms. Results: One person withdraw consent at baseline (OD). Two persons prematurely discontinued the study due to their own decision, both at 12 weeks (OD, and 1W). Three persons had confirmed VL >50 c/mL: 2 in 1W (both at 4 weeks, VL 780 and 29800 c/mL, no resistance mutations); and 1 in 3W (at 12 weeks, VL 60 c/mL, not amplified) but all returned to <50 c/mL on switching to OD as pre-scheduled. PWH with VL <50 c/mL (Snapshot ITT-exposed population) at 12 and 48 weeks were: OD, 9 (100%) and 8 (89%); 3W, 9 (90%) and 10 (100%); 2W, 10 (100%) and 10 (100%); 1W, 10 (100%) and 9 (90%). There were no significant differences in ultrasensitive VL, HIV reservoir, CD4 or CD8 cells, and hsCRP or IL-6 among arms. Although trough plasma and intracellular drug levels significantly decreased in 3W, 2W, and 1W relative to OD at 12 and 48 weeks, mean trough levels at 12 and 48 weeks in 3W and 2W, but not in 1W, were generally above the known inhibitory concentrations ( Table ). Conclusions: In virally suppressed PWH on BETAF OD, the strategy of reducing the BETAF OD dose to 3W, 2W, or 1W for 48 weeks was safe, well tolerated, and effective as compared with continuing OD. Consistent with subtherapeutic drug levels, the risk of viral failure was higher with 1W than with 2W or 3W; there was no emergent resistance and viral control was regained upon switching to OD.

Methods: The bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)- elderly study was an open-label, randomized, non-inferiority trial conducted at two sites in Kenya. HIV-1 positive adults ≥60 years old with HIV viral load (VL) <50 copies/mL for at least 12 weeks prior to enrollment while on any first line regimen were randomized 1:1 to switch to B/F/TAF or continue current ARV regimen (CAR). We report the key secondary outcomes at week 96 including proportion of participants with VL ≥50 copies/mL using the FDA snapshot algorithm with a 4% non-inferiority margin, the mean percentage change in lumbar spine BMD, safety and incident co-morbidities. ClinicalTrials.gov NCT05243602. Results: Between Feb and May 2022, 520 participants were randomized (260 B/F/TAF, 260 CAR) and a subset of 296 had BMD monitoring (143 B/F/ TAF, 153 CAR). All participants were black African, 267 (51%) were female and the median age was 64 years (range 60-79). Baseline characteristics were balanced between arms. At enrollment, 495 (95%) participants were on tenofovir disoproxil fumarate (TDF) and 179 (60%) of the BMD population had osteoporosis. At week 96, 7/260 participants (2.7%) in each arm had VL ≥50 copies/mL (difference [95% CI], 0% [-2.8 to 2.8]), meeting non-inferiority (Figure). The mean percentage change in lumbar spine BMD was +3.98% (SD 6.10) on B/F/TAF and +2.29% (SD 6.02) on CAR (difference [95% CI], 1.70 [0.25 to 3.14], p=0.021). There were no treatment-related serious adverse events (AEs) in either arm. Participants discontinuing study drug due to any AE were 1 (0.4%, due to Tuberculosis) on B/F/TAF and 30 (11.5%, due to declining kidney function) on CAR. Percentage change in creatinine clearance was 1.7 on B/F/ TAF and -3.5 on CAR. Percentage change in weight was 0 on B/F/TAF and -2.6 on CAR, 13.4% and 6.4% of participants on B/F/TAF and CAR respectively had >5% weight gain, 60/166 (51.7%) on B/F/TAF and 46/100 (49.1%) on CAR had incident hypertension, 69/207 (33%) on B/F/TAF and 58/218 (26.6%) on CAR had incident dyslipidemia. Conclusions: A first line switch strategy to B/F/TAF was effective and safe in a population of older African adults and associated with less requirement for treatment modification due to declining kidney function compared to CAR. Juan Tiraboschi 1 , Maria J. Crusells 2 , Pere Domingo 3 , Roberto Guerri-Fernandez 4 , Enrique Bernal 5 , Boris Revollo 6 , Maria-Jesus Vazquez 7 , Marta De Miguel 8 , Pablo Ryan 9 , Lucio Jesús Garcia Fraile Fraile 10 , Mar Masiá 11 , Jose L. Blanco 12 , Belen Alejos 13 , Esteban Martinez 12 , Adrian Curran 14 , for the PASO-DOBLE Study Team 1 Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain, 2 Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain, 3 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 4 Hospital del Mar, Barcelona, Spain, 5 Hospital General Universitario Reina Sofía, Murcia, Spain, 6 Institute for Health Science Research Germans Trias i Pujol, Badalona, Spain, 7 ViiV Healthcare, Madrid, Spain, 8 Fundación SEIMC-GeSIDA, Madrid, Spain, 9 Hospital Universitario Infanta Leonor, Madrid, Spain, 10 Hospital Universitario de La Princesa, Madrid, Spain, 11 Hospital General Universitario de Elche, Elche, Spain, 12 Hospital Clinic of Barcelona, Barcelona, Spain, 13 Independent Consultant, Madrid, Spain, 14 Hospital Universitari Vall d'Hebron, Barcelona, Spainn Background: The PASO-DOBLE study (ClinicalTrials.gov NCT04884139) demonstrated non-inferior efficacy and less weight gain when switching to DTG/3TC vs BIC/FTC/TAF in virologically suppressed people with HIV (PWH). We planned to assess subgroup analyses of efficacy (HIV RNA <50 copies/mL at 48 weeks) and clinically meaningful weight changes (>5% from baseline) by predefined baseline demographic, clinical and treatment characteristics. Methods: Clinically stable, virologically suppressed PWH on regimens containing ≥1 pill/day, boosters, or drugs with cumulative toxicity such as EFV or TDF were randomized (1:1) to switch to DTG/3TC or BIC/FTC/TAF stratifying by sex at birth and TAF at baseline. According to the statistical analysis plan, we calculated unadjusted differences with 95% confidence intervals DTG/3TC minus BIC/FTC/TAF in the proportions of PWH with: 1) HIV RNA <50 copies/mL, and 2) weight gain >5% in the exposed intention-to-treat population between study arms at 48 weeks according to sex at birth, age, race/ethnicity, previous AIDS, CD4 cells, and antiretrovirals at baseline. Results: Between 14-July-2021 and 24-March-2023, 553 PWH switched to DTG/3TC (n=277) or BIC/FTC/TAF (n=276), including 147 (27%) women and 155 (28%) with TAF at baseline. In general, there were consistent effects on efficacy across major subgroups. Significant differences in viral suppression favored DTG/3TC vs BIC/FTC/TAF in the following subgroups: age 35-50 years (9.6%, 95%CI 0.3 to 18.9), Latin-American ethnicity (11.8%, 95%CI 1.0 to 22.7), The figure, table, or graphic for this abstract has been removed. Switch to DTG/3TC vs B/F/TAF (PASO-DOBLE Study): Efficacy & Weight Changes by Predefined Subgroups

Poster Abstracts

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Switch of Virally Suppressed Adults ≥ 60 Years From First-Line ART to B/F/TAF: Week 96 Results Loice Ombajo 1 , Jeremy Penner 2 , Joseph Nkuranga 1 , Victor Mbewa 1 , Edwin Otieno 1 , Jared Mecha 1 , Simon Wahome 3 , Florentius Ndinya 4 , Rose Wafula 5 , Anton Pozniak 6 , for the B/F/TAF-Elderly Study Group 1 University of Nairobi, Nairobi, Kenya, 2 University of British Columbia, Vancouver, Canada, 3 Kenyatta National Hospital, Nairobi, Kenya, 4 Jaramogi Oginga Odinga Teaching & Referral Hospital, Kisumu, Kenya, 5 National AIDS and STI Prevention and Control Program, Nairobi, Kenya, 6 Chelsea and Westminster Hospital, London, UK Background: Antiretroviral options for older adults are limited by age related co-morbidities and drug toxicities. We evaluated whether a first line switch strategy in older adults maintains viral suppression while minimizing contribution to comorbidities.

CROI 2025 184