Pilot Study to Evaluate Efficacy and Safety of Switching to BIC/FTC/TAF in PWH With a Previous Virological Failure Under CAB/RPV LAI

Official title

Retrospective/Prospective Pilot Study to Evaluate Efficacy and Safety of Switching to BIC/FTC/TAF in PWH With a Previous Virological Failure Under CAB/RPV LAI

Overview

This study is a pilot, multi-center, observational retrospective-prospective study, with two different Parts, as follows: 1. Part 1(retrospective and prospective part): to evaluate efficacy and safety of switching to BIC/FTC/TAF in People living with HIV (PWH) who previously failed CAB/RPV LAI in the last three years and received in the last three years boosted PI since any INSTI mutations were detected on RNA and/or DNA through NGS at failure 2. Part 2 (prospective part only): to evaluate efficacy and safety of switching directly to BIC/FTC/TAF in PWH who failed CAB/RPV LAI without any RAMs on RNA and/or DNA through NGS considered of potential relevance for bictegravir Inclusion Criteria: * PWH with age \>18 years * PWH with a confirmed virological failure on CAB/RPV LAI in the last three years * PWH without RAMs versus FTC and TAF Study population: 30 subjects failing CAB/RPV LAI will be included in the study

Detailed description

BIC/FTC/TAF has been studied in treatment-naïve and virologically suppressed people with HIV (PWH) with a cumulative exposure of \>3.1 million person-years of treatment.

Cabotegravir/Rilpivirine (CAB/RPV) is the first long-acting injectable (LAI) regimen approved and could be a game-changer in the world of HIV treatment, as it is the first ever HIV drug combination that does not need to be taken every day. However, although data from randomized clinical trials demonstrated the non-inferiority efficacy of CAB/RPV LAI in PWH switching from triple therapies, a higher rate of emergent resistance associated mutations (RAMs) to INSTI and NNRTIs emerged. The risk of acquired RAMs may be even higher in clinical practice, outside the controlled conditions of clinical trials. Although the rate of virological failure is quite rare (1%-2%), resistance to these types of drugs (especially INSTI) is a major problem for PWH, as it severely limits the future treatment options. In the light of these considerations, it becomes important to understand if the reduced susceptibility is really relevant in clinical practice, identifying the remaining treatment options; are PIs the only possible choice or is there still room for INSTIs? In this sense, bictegravir has the longest dissociation time from the target among INSTIs (retaining its inhibitory activity against HIV replication for a longer time) and showed an improved resistance profile compared with other INSTIs, including DTG, in vitro. Moreover, a recent in vitro phenotype assessment of isolates with a CAB failure-like patterns of RAMs showed that 54% and 40% of the isolates maintained susceptibility or partial susceptibility to bictegravir, respectively.

Finally, it is currently unknown if INSTI mutations will persist on DNA or if they will disappear.

This study is a pilot, multi-center, observational retrospective-prospective study, that will include 30 subjects failing CAB/RPV LAI. The primary objective is to describe drug efficacy at week 24. Secondary objectives are to describe drug efficacy at week 48, to describe drug failure at week 24 and week 48, to describe immunological changes at week 24 and week 48, to describe drug safety and to describe changes in patient's quality of life.

Primary outcome measures

• Rate of virological suppression (proportion of PWH with HIV-RNA <50 copies/mL) at week 24 (after the switch to BIC/FTC/TAF) [Time frame: From enrollment to week 24]

Secondary outcome measures (6)

• Rate of virological suppression (proportion of PWH with HIV-RNA <50 copies/mL) at week 48 [Time frame: From enrollment to week 48]
• Rate of virologic failure (2 consecutive VL ≥50 copies/mL) at weeks 24 and 48 [Time frame: From enrollment to week 48]
• Change from baseline in CD4+ T-cell count (absolute and %) and CD4/CD8 ratio at weeks 24 and 48 [Time frame: From enrollment to week 48]
• WHO grade 3-4 toxicity [Time frame: From enrollment to week 48]
• Rate of discontinuation of BIC/FTC/TAF for AEs [Time frame: From enrollment to week 48]
• Change in treatment satisfaction after the switch to BIC/FTC/TAF (changes in HIVTSQ) [Time frame: From enrollment to week 48]

Eligibility criteria

Inclusion criteria

• PWH with age >18 years
• PWH with a confirmed virological failure on CAB/RPV LAI in the last three years
• PWH without RAMs versus FTC and TAF

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Other

Study locations

Italy · 1 center

• AOU Modena — Modena

Publications

• Jongen VW, Wit FWNM, Boyd A, van Eeden A, Brouwer AE, Soetekouw R, El Moussaoui R, Stalenhoef J, Sigaloff KCE, Mudrikova T, Gisolf J, Burger D, Wensing AMJ, van der Valk M; ATHENA National Observational HIV Cohort. Effectiveness of bi-monthly long-acting injectable cabotegravir and rilpivirine as maintenance treatment for HIV-1 in the Netherlands: results from the Dutch ATHENA national observation PMID 39779044
• Iannone V, Lombardi F, Ciccullo A, Lamanna F, Salvo PF, Sanfilippo A, Baldin G, Borghetti A, Torti C, Di Giambenedetto S. Real World Data from an Italian Outpatient Clinical Setting and from Home Care Assistance of Treatment-Experienced PWH Switching to CAB + RPV Regimen: A Prospective Observational Study. AIDS Behav. 2025 Apr;29(4):1228-1234. doi: 10.1007/s10461-024-04597-4. Epub 2025 Jan 9. PMID 39779624
• Mchantaf G, Chaillon A, Charre C, Melard A, Gardiennet E, Guinard J, Prazuck T, Guillaume C, Mariaggi AA, Bois J, Hocqueloux L, Avettand-Fenoel V. Learning From Full Characterization of HIV Proviruses in People Receiving Long-Acting Cabotegravir/Rilpivirine With a History of Replication on the Antiretroviral Classes. Open Forum Infect Dis. 2024 Dec 24;12(1):ofae748. doi: 10.1093/ofid/ofae748. eCol PMID 39872809
• McCall KL, Cabral DL, Coghlan JF, Concepcion AM, Denimarck KE, Shalumov SS. Therapeutic failure reported with HIV long-acting injectables: An analysis of the FDA Adverse Event Reporting System from 2021 to 2024. HIV Med. 2025 Jan;26(1):173-178. doi: 10.1111/hiv.13709. Epub 2024 Sep 5. PMID 39234659
• Perez Navarro A, Nutt CT, Siedner MJ, McCluskey SM, Hill A. Virologic Failure and Emergent Integrase Strand Transfer Inhibitor Drug Resistance With Long-Acting Cabotegravir for HIV Treatment: A Meta-analysis. Clin Infect Dis. 2025 Sep 16;81(2):274-285. doi: 10.1093/cid/ciae631. PMID 39724249
• Cutrell AG, Schapiro JM, Perno CF, Kuritzkes DR, Quercia R, Patel P, Polli JW, Dorey D, Wang Y, Wu S, Van Eygen V, Crauwels H, Ford SL, Baker M, Talarico CL, Clair MS, Jeffrey J, White CT, Vanveggel S, Vandermeulen K, Margolis DA, Aboud M, Spreen WR, van Lunzen J. Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: a multivariable analysis. AIDS. 2021 Jul 1 PMID 33730748

Identifiers

NCT: NCT07620652 · BICPREVIR · 2573

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗