The PIBIK trial has demonstrated that switching virologically suppressed HIV patients from boosted protease inhibitor (bPI) therapy to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) maintains effectiveness despite historical nucleoside reverse transcriptase inhibitor (NRTI) resistance.
In this phase IV, multicenter, open-label study conducted across seven centers in England, 72 participants with documented NRTI resistance mutations were randomized to either immediate switch to B/F/TAF or delayed switch after 24 weeks of continued bPI therapy.
Efficacy Results
The trial achieved its primary endpoint with 100% (33/33) of immediate switch participants maintaining viral suppression at 24 weeks compared to 97.4% (38/39) in the delayed switch group. This high level of suppression was sustained through 48 weeks of follow-up.
Notably, the regimen remained effective across various resistance patterns, including patients with M184V/I mutations and up to two thymidine analogue mutations (TAMs). Among participants, 29.2% had M184V/I mutations, while 43.1% had one TAM with or without M184V/I, and 20.8% had two TAMs with or without M184V/I.
Safety and Tolerability Profile
During the first 24 weeks, adverse events were reported in 75.8% of immediate switch participants versus 61.5% in the delayed switch group. Drug-related adverse events were more common in the B/F/TAF arm (30.3%) compared to the bPI arm (2.6%).
Common side effects included:
- Headaches
- Weight gain (median 2.5 kg in immediate switch arm)
- Central nervous system-related events
- Sleep disturbances
- Mood changes
Six participants discontinued the study, with four B/F/TAF discontinuations due to drug-related adverse events including weight gain, worsening depression, and hypersensitivity.
Metabolic and Laboratory Outcomes
Participants switching to B/F/TAF showed improvements in lipid parameters, with decreases in total cholesterol, non-HDL cholesterol, and triglycerides. However, there were increases in HbA1c and weight compared to those remaining on bPI therapy.
Renal function, assessed by estimated glomerular filtration rate (eGFR), showed slight improvement in the B/F/TAF group while declining in those continuing bPI therapy.
Clinical Implications
These findings expand the evidence supporting B/F/TAF's effectiveness in patients with historical NRTI resistance beyond just M184V/I mutations. The study suggests B/F/TAF can maintain viral suppression even in the presence of multiple resistance mutations, including those affecting tenofovir susceptibility.
The results are particularly relevant for treatment-experienced patients with documented resistance who might benefit from simplifying their regimen. However, careful monitoring of metabolic parameters and potential side effects is warranted, particularly in the initial months after switching.
