Rob Burton
Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.
The next INSTI on the block?
Greetings from Seattle. I would like to start by thanking ASHM for giving me the opportunity to attend this world-class conference and also thank the readers for taking time to read my blog.
Gilead dominated the morning session that I attended, presenting 2 novel drugs in different stages of development. I will talk about the more conventional of the novel drugs, which is now undergoing phase 3 clinical trials (4 active trials).
Bictegravir (BIC) is a novel, once daily INSTI. In-vitro studies have demonstrated it’s high level of activity against wild-type and many INSTI-resistant viruses. The drug has good oral absorption and an excellent PK profile, with a trough level well above IC95. The drug is mainly metabolised through CYP3A4 and UGT1A1 and has a favourable DDI profile. Similar to dolutegravir (DTG), there can be increased metformin levels (39%) and potentially clinically relevant interactions in the presence of potent inducers such a rifampicin. The 50mg once daily BIC dose was selected in coformulation with FTC/TAF as a single tablet regimen to progress in further studies.
Paul Sax then presented the 48 week data from a relatively small randomised double-blind active control study. 98 participants were included (from 125 screened) BIC = 65, DTG = 33. Patients with chronic hepatitis (B and C) were excluded. Overall rates of viral suppression were excellent in both groups at 24 and 48 weeks. In the BIC group, viral suppression (Defined as VL < 50 copies/ml) was 97% at 24 and 48 weeks. There were 2 discontinuations in both arms (1 lost to follow-up in each arm, 1 non-compliance in DTG, 1 AE in BIC). In terms of adverse events, diarrhoea was the most common side-effect reported in 12% of subjects in the BIC arm. Overall, AE profiles and lab abnoralities were reassuring. A minor decline in eGFR of -7.0 ml/min was observed BIC. No treatment-emergent mutations (INSTI or NRTI) were noted through week 48 in either group.
In summary, bictegravir is an exciting novel INSTI which has moved on to phase 3 clinical trials. Should it progress and eventually receive approval, it will be coformulated with FTC/TAF in a single tablet regimen, joining what is becoming a rather crowded market.