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HIV Rx: After Truvada Comes TAF

HIV Rx: After Truvada Comes TAF

In 2001, the US FDA-approved tenofovir disoproxil fumarate (TDF), a nucleotide analogue of adenosine monophosphate, for the treatment of HIV when combined with other antiretrovirals.  TDF is a pro-drug, which is converted to tenofovir after diester hydrolysis and subsequent cellular diphosphorylation to the active form, tenofovir diphosphate. Since its approval, TDF has been coformulated with emtricitabine, with elvitegravir plus cobicistat plus emtricitabine, and with rilpivirine plus emtricitabine. The combination of TDF plus emtricitabine, marketed under the name of Truvada,® is one of the most widely-prescribed antiretroviral fixed-dose combination products, and is one of the components of four of the five regimens recommended by the Department of Health and Human Services (DHHS) Antiretroviral Guidelines Panel.1 In addition, it is the only FDA-approved antiretroviral product for pre-exposure prophylaxis (PrEP).

Tenofovir molecule. © Unfortunately, Truvada® is associated with increased risk of kidney injury and loss of bone mineral density. Over the last several years, a different formulation of tenofovir, tenofovir alafenamide (TAF), has been developed and put into multiple clinical trials. We heard about several of these trials at the recently-completed IDWeek conference in San Diego. Dr. Melanie Thompson, from Atlanta, presented the 48-week results of the Gilead Sciences-sponsored GS-US-292-0109 trial that looked at the efficacy and safety of the combination of TAF plus elvitegravir (E) plus cobicistat (C) plus emtricitabine (F) [E/C/F/TAF] versus [E/C/F/TDF] in virologically-suppressed HIV-infected persons.2 The results showed that the TAF group maintained virologic suppression to <50 copies/mL as well as the TDF group, and had statistically significant less renal tubular proteinuria and improved bone mineral density compared to the TDF group. However, only 9% of the 459 persons enrolled in the trial were women, a group of particular interest for the endpoint of bone mineral density loss.

Two other presentations on TAF-containing products in that same session deserve mention:

1) Dr. Greg Huhn, of Chicago, presented the results of a Gilead Sciences-sponsored trial of HIV-infected persons with 2-antiretroviral class resistance comparing [E/C/F/TAF] plus darunavir 800mg daily versus continued current therapy.3 The results showed favorable virologic suppression rates and good tolerability at 48 weeks in the TAF group compared to the current therapy group. 

2) Dr. Joseph Custidio, of Gilead Sciences, presented a very important pharmacokinetic study of TAF-containing products including rilpivirine-based, elvitegravir-based, and emtricitabine-based, that showed no clinically relevant drug-drug interactions with any of the products when combined with ledipasvir/sofosbuvir (Harvoni®), the most commonly-used treatment for persons infected with hepatitis C virus.

These trials are important because the FDA approval of several TAF-containing co-formulated products is likely to occur very soon. Approval of [E/C/F/TAF] is expected in November of this year, followed by the approval of rilpivirine/emtricitabine/TAF and emtricitabine/TAF in March – April of 2016. Approval of darunavir/cobicistat/TAF likely will follow in late 2016. 

The era of TAF is here.


1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services.  Accessed 13 October 2015; Table 6.

2. Thompson M, Morales-Ramirez J, McDonald C, et al.  Switching from a Tenofovir Disoproxil Fumarate (TDF) to a Tenofovir Alafenamide (TAF)-Based Single Tablet Regimen (STR): Week 48 Data in HIV-1 Infected Virologically Suppressed Adults.  Abstracts of IDWeek; 07 – 11 October 2015, San Diego; Session 125; Abstract Number 725.

3. Huhn G, Tebas P, Gallant J, et al.  Strategic simplification: the efficacy and safety of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) plus darunavir (DRV) in treatment-experienced HIV-1 infected adults (NCT01968551).  Abstracts of IDWeek; 07 – 11 October 2015, San Diego; Session 125; Abstract Number 726.

4. Custodio J, Doyle E, Pang PS, et al.  Lack of drug interactions between boosted and unboosted tenofovir alafenamide-based antiretroviral single tablet regimens (emtricitabine/rilpivirine/tenofovir alafenamide and elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) and the anti-HCV single tablet regimen ledipasvir/sofosbuvir.  Abstracts of IDWeek; 07 – 11 October 2015, San Diego; Session 124; Abstract Number 727.


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