Patient with extensive treatment history and resistance.
DHHS and Liverpool suggest BIC should 'not be coadministered' with ATV/c due to increase of 300% in exposure. However there were no grade 3-4 toxicities in the ATV-BIC drug drug interaction studies.
1.Would you consider using ATV/c with BIC/TAF/FTC in order to minimize pill burden and preserve once/daily dosing in a person with poor treatment adherence and extensive resistance?
2.Would you consider the ATV/c or ATV/r with DTG regimens and dose the DTG daily with expectation of increased DTG exposures due to the drug interactions?
Below is a (very rough) synthesis of a discussion involving a small number of consultants with the national HIV Warmline/Natl Clinician Consultation Center (UCSF):
1- First, thank you for sharing this case -- complicated because of the treatment history/mutations identified but also very interesting areas for learning and dialogue
2- In response to the question regarding co-use of ATV/c with BIC/F/TAF: overall, our discussants were not so enthusiastic/comfortable with this combo although we do recognize and acknowledge its very real appeal in a situation where a patient strongly prefers a once-daily regimen. Because of the limited data available regarding this interaction, in addition to emerging awareness of the tolerability and toxicity profile of BIC (and TAF here too, if ATV/c will be used concurrently), we were hesitant about this option. Although AUC increase of 300% was observed in a small participant sample with no grade 3-4 events, it's unclear how this finding might translate into clinical practice and how we could/should counsel patients about this combo. Our consultants really haven't used ATV/cobi + BIC/F/TAF in their personal practices; 1 person has (their pt had possible DRV allergy). Additionally, for someone with a history of intermittent ARV adherence and multi-class/multi-drug resistance, ATV/c + BIC/F/TAF just seems like it would require a bit of a leap of faith... plus close clinical + lab monitoring.
3- In response to the question re: co-use of boosted ATV with DTG, we would similarly be cautious with trying to use once-daily DTG in this setting -- already know that INI-associated mutations have been identified. Without understanding better what DTG bid might look like compared to BIC in this scenario, we're not so hopeful that a modest drug interaction would increase DTG exposures to the point of being able to 'overcome' the mutations identified.
Our team had a much more drawn-out discussion when actually trying to land on an optimal regimen/preferred option(s) to consider, as multiple combos should be viable. A few thoughts: would a phenotype be helpful to better characterize PI activity? How strongly do the patient and treating provider feel about once-daily vs twice-daily? Happy to chat more about this piece of the case (nccc.ucsf.edu, #s can be found on our website), but ultimately the most "successful" combo will be the one the patient takes.
Thanks so much for sharing!
The NCCC HIV Warmline team