by Carolyn Chu, MD, MSc, AAHIVS, AAHIVM Chief Medical Officer
September 26, 2023
Podzamczer D, Imaz A, Lopez-Lirola A, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) plus darunavir/cobicistat in heavily antiretroviral-experienced, virologically suppressed HIV-infected adults receiving complex regimens. J Antimicrob Chemother. 2023 Sep 19; dkad285. doi: 10.1093/jac/dkad285. PMID: 37725999
Sixty-three participants were enrolled in this single-arm, open-label multi-center pilot evaluating efficacy and safety of BIC/F/TAF + DRV/cobicistat as a switch regimen. Prior to switch, participants had been taking combinations involving three or more ARV classes and three or more pills/day. People with known or suspected INSTI resistance were excluded, as well as people with a darunavir resistance mutation score of ≥15 per the Stanford HIV Drug Resistance Database. Median time on ART was 24.3 years, with a current median of 4 pills daily (some took as many as 10 pills/day). Ten people switched from a regimen which included twice-daily boosted darunavir. Proviral DNA from 39 (62%) participants revealed that 85% had resistance associated mutations at baseline; calculated GSS using DNA genotype results indicated that 95% of participants had two or more sensitive ARVs. After 48 weeks, 95% maintained an undetectable VL. Three people discontinued therapy due to adverse events including rash, headache and mood symptoms (anxiety), and grade 2 eGFR decrease. The participant who experienced eGFR decrease had a history of low eGFR attributed to prior TDF use. Pre-dose bictegravir concentrations increased by 11-31% compared with reference Cmin values and were 24% higher than reference Cmax. Both treatment satisfaction and perception of adherence increased.
Although this was a single-arm study involving a fairly uniform patient demographic (95% were assigned male at birth and all sites were in Spain), all participants were switching from complex regimens involving multiple pills. No virologic failures were observed over 48 weeks of follow-up and the new combination appeared to be highly acceptable among participants, with few discontinuations. Given various drug interaction concerns about the co-use of bictegravir, TAF, and cobicistat, the inclusion of bictegravir levels in this analysis is informative (N.B. TAF levels were not measured). Due to the high prevalence of kidney disease and TDF exposure among many older PWH, as well as the known interaction between bictegravir and cobicistat and certain renal transporters, further investigation (including potential use of additional biomarkers) into the safety of this switch regimen are needed. Nevertheless, results of this pilot help support the consideration of additional, larger studies examining this combination.
View archived Clinical Research Update entries here.