Bictegravir/Emtricitabine/Tenofovir Alafenamide in Older Individuals With HIV

Results of a 96-Week, Phase 3b, Open-Label, Switch Trial in Virologically Suppressed People >65 Years of Age

Franco Maggiolo; Giuliano Rizzardini; Jean-Michel Molina; Federico Pulido; Stephane De Wit; Linos Vandekerckhove; Juan Berenguer; Michelle L. D'Antoni; Christiana Blair; Susan K. Chuck; David Piontkowsky; Hal Martin; Richard Haubrich; Ian R. McNicholl; Joel Gallant

Disclosures

HIV Medicine. 2023;24(1):27-36. 

In This Article

Abstract and Introduction

Abstract

Objectives: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is an effective treatment for HIV-1 infection; however, clinical trial data in older people living with HIV (PLWH) are lacking. The primary 24-week and secondary 48-week analyses of study GS-US-380-4449 (NCT03405935), which assessed the efficacy and safety of switching to B/F/TAF in older PLWH, have been published. Here we report the results of the final 96-week analyses from the study.

Methods: In this 96-week, phase 3b, open-label, single-arm trial, virologically suppressed PLWH aged ≥65 years switched from elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen to B/F/TAF. Viral suppression, resistance, immune response, safety, tolerability and adherence were evaluated through week 96.

Results: Of 90 participants screened, 86 were enrolled and switched to B/F/TAF. No participants had HIV-1 RNA ≥50 copies/ml (by FDA Snapshot algorithm) at weeks 72 or 96; virologic suppression rates were 94.2% (81/86; 95% CI 87.0–98.1) and 74.4% (64/86; 95% CI 63.9–83.2), respectively. No treatment-emergent resistance was observed, and CD4 counts remained stable. There were no study drug-related serious adverse events. Three participants experienced drug-related treatment-emergent adverse events that led to premature drug discontinuation. There were no clinically relevant changes from baseline to week 96 in fasting lipid parameters, and the median change in body weight at week 96 was 0.0 kg (IQR −2.3, 2.0). Median self-reported adherence was 100% (IQR 100–100%).

Conclusions: Switching to B/F/TAF is an effective long-term option for virologically suppressed adults ≥65 years of age, with favourable safety and tolerability profiles in this population.

Introduction

Older people living with HIV (PLWH) represent an important and growing population around the world. In the USA in 2018, 51% of the HIV-diagnosed population were ≥50 years of age, with 10% aged ≥65 years.[1] By 2030, the median age of PLWH in the USA is projected to increase from 50 to 53 years.[2] Furthermore, overall life expectancy among 20-year-old PLWH has greatly increased, with one study reporting improvement from 11.8 years (1988–1991) to 54.9 years (2006–2013).[3]

Older PLWH experience specific medical challenges not faced by younger PLWH. By 2030, it is predicted that 36% of PLWH will have two or more comorbidities,[2] and the likelihood of non-HIV illness increases with age.[4] One US study found that PLWH have rates of non-HIV conditions and non-antiretroviral therapy (ART) use that are comparable to those of people without HIV who are 5–10 years their senior.[5] Polypharmacy is common in PLWH ≥50 years of age, with one study finding that this population was prescribed an average of 11.6 concomitant non-ART medications and that over one-third received 16 or more medications.[6] As a result of these increased levels of comorbidities and polypharmacy, drug–drug interactions (DDIs) tend to be more common in older PLWH,[7] and additional scrutiny may be necessary to limit the risk of ART-related DDIs in this population. It is critical that the efficacy, safety and adherence of ART regimens are investigated in older PLWH; however, clinical trial data in this population are notably lacking.

Two- and three-drug ART regimens are recommended for the initial treatment of HIV infection.[8,9] Three-drug regimens usually consist of two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (INSTI).[8,9] Individuals may switch ART for a number of reasons, including to reduce pill burden or to simplify the dosing regimen, as well as to avoid side effects or decrease the risk of drug–food interactions or DDIs.[8] Switching ART regimens may occur more frequently in older PLWH, who have a higher prevalence of comorbidities and polypharmacy.

B/F/TAF, a coformulation of bictegravir (B), emtricitabine (F) and tenofovir alafenamide (TAF), is indicated as a complete regimen for the treatment of HIV-1 infection in individuals without present or past evidence of viral resistance to the INSTI class or to the individual components of the regimen.[10,11] Bictegravir is a potent, unboosted, once-daily INSTI with a favourable pharmacokinetic profile.[12] The combination of emtricitabine and either TAF or tenofovir disoproxil fumarate (TDF) is commonly recommended as an NRTI backbone.[8,9] TAF is a newer alternative to TDF with a more favourable bone and renal safety profile,[13] and is an effective treatment for hepatitis B.[14] B/F/TAF has been shown to have an acceptable safety profile and to be well tolerated and effective in treatment-naïve PLWH, virologically suppressed PLWH, and suppressed PLWH with pre-existing NRTI resistance.[15–21] Additionally, switching to B/F/TAF has been demonstrated to reduce the risk of DDIs in treatment-experienced individuals.[22]

The present 96-week phase 3b study evaluates the efficacy and safety of switching to B/F/TAF from an elvitegravir (E)/cobicistat (C)/F/TAF fixed-dose or TDF-containing regimen in virologically suppressed PLWH ≥65 years of age. To our knowledge, this is the first European trial investigating the efficacy and safety of B/F/TAF in older PLWH. Previously published data from this study indicated that switching to B/F/TAF was effective and well tolerated through 48 weeks.[18] Here, we report the final 96-week analysis performed at trial completion.

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