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

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

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

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.

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