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Chief, Division of HIV Medicine
Harbor-UCLA Medical Center
Professor of Medicine
David Geffen School of Medicine at UCLA
Los Angeles, California
Eric S. Daar, MD, has disclosed that he has received consulting fees from Genentech, Gilead Sciences, Merck, and ViiV and funds for research support from Gilead Sciences, Merck, and ViiV.
The treatment of HIV in patients with end-stage renal diseases has typically required complex regimens with dose adjustments. Since the prevalence of end-stage renal disease is relatively high in patients with HIV and is likely to increase with an aging population, an effective, safe, and convenient regimen for this population of patients is sorely needed. Fortunately data are accumulating on such simplified regimens for these patients, including those involving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), bictegravir/emtricitabine/TAF, and abacavir/lamivudine/dolutegravir. Here I discuss new data that have been recently presented on bictegravir/emtricitabine/TAF to help us assess the efficacy and safety this strategy.
Background: Previous Data on Simplified Regimens for Individuals With End-stage Renal Disease
A previous study reported by Eron and colleagues demonstrated that E/C/F/TAF given once daily to 55 individuals on hemodialysis for at least 6 months was safe and efficacious. Indeed, no grade ≥ 3 adverse event was deemed treatment related by the site investigators. They further noted that there were lower plasma tenofovir levels than those seen in typical dose-adjusted weekly tenofovir disoproxil fumarate in this patient population. Although these data suggested that E/C/F/TAF could be used as a single-tablet option for those on hemodialysis, it was limited by the fact that this regimen is no longer considered a preferred first-line option due to tolerability disadvantages and a lower barrier to resistance than newer agents.
New Data From IDWeek 2020
At IDWeek 2020, Eron and colleagues reported results from an open-label extension study of those on hemodialysis who were virologically suppressed on daily E/C/F/TAF for at least 96 weeks. Ten participants switched to bictegravir/emtricitabine/TAF with 48 weeks of follow-up. They found that bictegravir concentrations were lower than those seen in people with HIV not on hemodialysis, although troughs remained well above the protein-adjusted 95% effective concentration for wild-type virus. Emtricitabine and tenofovir concentrations were higher than previously seen with E/C/F/TAF use in those with normal renal function. However, tenofovir levels were lower than those seen historically in hemodialysis patients receiving dose-adjusted, once-weekly tenofovir disoproxil fumarate. Overall tolerability was good with no serious adverse events related to study drugs. In addition, all 10 participants had HIV-1 RNA < 50 copies/mL throughout 48 weeks of follow-up.
Benefits and Limitations of the IDWeek 2020 Data
Although the IDWeek authors conclude that simplification to bictegravir/emtricitabine/TAF offers a safe and effective regimen for those on hemodialysis, the data remain somewhat limited. First, data are only available for 10 individuals with 48 weeks of follow-up. Second, as was the case in the original study of E/C/F/TAF in patients on hemodialysis, no information was available on the potential impact on residual renal function that may have been present in select study participants. This is potentially relevant since there are data showing that maintaining even low levels of residual renal function can be clinically important. As a result, when considering these new data, it is important to consider a risk–benefit assessment for use of any nephrotoxic agent in those on hemodialysis with residual renal function. Finally, data are limited as to how TAF might influence bone mineral density in this patient population. Ultimately, these potential concerns must be balanced with the convenience associated with using simplified regimens in patients on hemodialysis.
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