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Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection

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Abstract

Darunavir/cobicistat/emtricitabine/tenofovir AF (Symtuza®) is the first protease inhibitor (PI)-based single-tablet regimen (STR) available for the treatment of adults and adolescents (aged ≥ 12 years) with HIV-1 infection. It combines the PI darunavir (which has a high genetic barrier to resistance) with the pharmacokinetic booster cobicistat and the nucleos(t)ide reverse transcriptase inhibitors emtricitabine and tenofovir alafenamide (tenofovir AF), the latter being associated with less off-target tenofovir exposure than its predecessor tenofovir disoproxil fumarate (tenofovir DF). Over 48 weeks in phase 3 trials, darunavir/cobicistat/emtricitabine/tenofovir AF was noninferior to darunavir/cobicistat plus emtricitabine/tenofovir DF in establishing virological suppression in antiretroviral therapy (ART)-naïve adults and, likewise, was noninferior to an ongoing boosted PI, emtricitabine plus tenofovir DF regimen in preventing virological rebound in virologically-suppressed, ART-experienced adults. Resistance did not emerge to the STR components, with the exception being an emtricitabine resistance-associated mutation (RAM) [M184I/V] in one of seven recipients who experienced virological failure (although M184V was a minority variant at screening in this patient). Darunavir/cobicistat/emtricitabine/tenofovir AF was generally well tolerated, with renal and bone profile improvements but less favourable effects on some lipids versus tenofovir DF-based regimens. Thus, although longer-term and cost-effectiveness data would be beneficial, darunavir/cobicistat/emtricitabine/tenofovir AF is a welcome addition to the STRs available for the treatment of adults and adolescents with HIV-1 infection, being the first to combine the high genetic resistance barrier of darunavir with the renal/bone profile of tenofovir AF, thus expanding the patient population for whom an STR may be suitable.

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Acknowledgements

During the peer review process, the manufacturer of darunavir/cobicistat/emtricitabine/tenofovir AF was also offered the opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Emma D. Deeks

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Correspondence to Emma D. Deeks.

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The preparation of this review was not supported by any external funding.

Conflict of interest

Emma Deeks is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: C. Godfrey, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; F. Maggiolo, Division of Infectious Diseases, ASST Papa Giovanni XXIII, Bergamo, Italy; M. Nelson, Imperial College School of Medicine, London, UK.

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Deeks, E.D. Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection. Drugs 78, 1013–1024 (2018). https://doi.org/10.1007/s40265-018-0934-2

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