Tenofovir alafenamide, emtricitabine, elvitegravir, and cobicistat combination therapy for the treatment of HIV

ABSTRACT

Introduction: Tenofovir alafenamide (TAF) is a novel prodrug of the nucleotide analogue reverse-transcriptase inhibitor, tenofovir. TAF has been co-formulated with emtricitabine (FTC), elvitegravir (EVG) and the EVG metabolic enhancer, cobicistat (COBI) as a single-tablet regimen being the first TAF-containing antiretroviral combination available.

Areas covered: This article summarizes the available information on the pharmacology of the novel compound TAF and overviews TAF/FTC/EVG/COBI use for HIV-1 infected patients, with specific focus on clinical efficacy and safety data. Information sources include peer-reviewed scientific literature, conference proceedings and publically available regulatory reports. Compared to tenofovir disoproxil fumarate, TAF results in higher concentrations of the active metabolite tenofovir diphosphate within lymphoid cells, whereas plasma tenofovir exposure is about 90% lower. The efficacy and safety of TAF/FTC/EVG/COBI in treatment-naïve HIV-infected patients has been assessed in phase-III randomized trials, showing non-inferior virological suppression in comparison with TDF/FTC/EVG/COBI, and significantly lower renal and bone toxicity. In addition, TAF/FTC/EVG/COBI has demonstrated efficacy and safety as a switching strategy in suppressed HIV-1 infected individuals, including those with mild or moderate renal impairment.

Expert commentary: Approval of the single-tablet TAF/FTC/EVG/COBI regimen is an important advance in HIV therapy, as it is associated with very high efficacy and a better kidney and bone safety profile compared to TDF-containing regimens due to the incorporation of TAF.

KEYWORDS:

• Tenofovir alafenamide
• elvitegravir
• cobicistat
• antiretroviral therapy
• HIV-1 infection

Information resources

Mechanistic studies: 15, 26, 27, 38, 39

Phase I and Phase II studies and pharmacokinetics data: 16, 17, 40, 48, 51

Efficacy and safety data from Phase III clinical trials: 17-19, 47-50

Resistance data: 16-17, 47, 49, 52-54

Declaration of interest

A. Imaz has received financial compensation for lectures, consultancies, and educational activities or funds for research from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme, and ViiV Healthcare.

D. Podzamczer has received research grants and/or honoraria for advisories and/or conferences from, ViiV Healthcare, BMS, Abbott, Gilead, Janssen, and Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.