Tenefovir Alafenamide Fumarate (TAF) Sign-On Letter to Gilead
Treatment Action Group, HIV i-Base, and Project Inform
Tenefovir Alafenamide Fumarate (TAF) Sign-On Letter to Gilead Sciences
June 13, 2013
John C. Martin
Chief Executive Officer
333 Lakeside Drive
Foster City, CA 94404
Dear Mr. Martin:
With a phase II clinical trial of tenofovir alafenamide fumarate (TAF) yielding encouraging preliminary results and regulatory planning for TAF-inclusive fixed-dose combinations (FDCs) under way, we are compelled to reach out to you regarding the need for a stand-alone formulation of the drug.
We are concerned that Gilead’s current development plans, as we understand them, might limit TAF to a component of FDCs only. Though this exemplifies Gilead’s leadership in manufacturing simplified and convenient innovator company antiretroviral (ARV) regimens, it overlooks the potential importance of a stand-alone TAF formulation for use in combination with a variety of non-Gilead agents—notably low-cost generic ARVs in low-, middle-, and high-income countries—and as a component of tailored regimens for treatment-experienced people living with HIV, including those with mutated strains conferring resistance to tenofovoir disoproxil fumarate (TDF).
Based on our communications with senior Gilead staff, it is our understanding that TAF’s regulatory plans are limited to an FDC containing elvitegravir, cobicistat, emtricitabine, and TAF; an FDC containing darunavir, cobicistat, emtricitabine and TAF; and, possibly, an FDC containing emtricitabine and TAF. By extension, we are under the strong impression that a stand-alone formulation of TAF is not a part of Gilead’s development plans for the drug.
Stand-Alone TAF for First-Line Treatment
Activists and the scientific community have known about the potential benefits of TAF, over those of tenofovir disoproxil fumarate (TDF), for twelve years; it is disappointing that its clinical development was delayed until the twilight of TDF’s patent protection. Still, the encouraging interim 24-week analysis from Study GS-US-292-0102, presented at the 20th Conference on Retroviruses and Opportunistic Infections, indicate that TAF shows significant potential as an effective alternative to TDF in first-line therapy regimens, with a potentially reduced impact on bone mineral density, serum creatinine, and eGFR.
The value of a stand-alone formulation of TAF cannot be overstated, and we urge Gilead to figure this into its regulatory plans for the drug, as the potential benefits for millions living with HIV may be significant.
Many providers and people living with HIV prefer FDCs. Yet there is a paucity of prospective clinical trial data supporting their potential advantages—either in adherence outcomes or biomarker endpoints—over once-daily, multiple-pill regimens. Moreover, of the four preferred initial combination regimens for ARV-naive HIV-infected adults and adolescents specified in the U.S. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, two require three tablets once a day and one requires twice-daily dosing. In effect, making TAF available as a stand-alone agent does not necessarily preclude its potential acceptance as a preferred first-line agent.
Going forward, we anticipate that generic efavirenz will be considered as a preferred first-line component of ARV therapy, combined with an innovator FDC (e.g., TDF/emtricitabine) or generic lamivudine plus TDF. Rochelle Walensky, MD, and colleagues project that uptake of these regimens could yield substantial cost savings during the first year of use in the United States alone, a factor guidelines authors, prescribers, people living with HIV, and payers now need to contend with—along with an ARV product’s efficacy, safety, and dosing convenience—in determining use.
We need to recognize that a shift toward generic ARVs is not so much a desire as it is a necessity and that the two-tier access to choice of ARVs in the United States—based on insurance coverage and ability to pay—will possibly widen further, potentially putting premium products such as TAF-inclusive FDCs out of reach for many. In Europe, national health systems have also had to make antiretroviral choices based on cost.
For these individuals, for whom generic-based therapy is either the most desirable or economically feasible, ensuring access to the safest, most effective regimen components is an imperative. It is therefore necessary that stand-alone TAF be studied and made available for use in combination with generic efavirenz, generic lamivudine, and other generic versions of HHS-preferred and -alternative ARVs with patents set to expire over the next five years.
TAF’s potential safety advantages and comparable efficacy, versus TDF, are also considerable in resource-poor countries, where TDF has emerged as a preferred component of first-line therapy. Yet in these settings, where highly effective ARV therapy is available for less than US$200 per patient, per year, the emphasis is now on developing and securing access to stand-alone agents and FDCs with ideal target product profiles: treatment that is simple, tolerable, durable, universal, and affordable. In these settings, there are also considerable numbers of children and adolescents who need treatment. TAF’s relatively low milligram dose—making co-formulation easier—and the possibility of reduced bone toxicity, could make it an important ARV for these individuals.
At the 2nd Conference on Antiretroviral Dose Optimization (CADO 2), held in April 2013 in Cape Town, there was a very strong interest in TAF as a potential component of an ideal target regimen. We appreciate Gilead’s commitment to ensuring access to antiretroviral products in low- and middle-income countries over the past decade. Through work with generic licensing partners, the Medicines Patent Pool, and other stakeholders, the price of TDF has reduced by almost 75 percent since 2006, both as a stand-alone and in FDCs that are not always the same as the innovator products.
Should TAF be confirmed to have safety advantages over TDF, its value as a component of low-cost regimens—notably those employing efavirenz and lamivudine—will need to be studied for superiority over existing first-line options. However, this will require the development, evaluation, regulatory approval, and market availability of TAF as a stand-alone component of combination ARV therapy in the United States. We implore Gilead to consider this, considering TAF’s potential in ongoing efforts to further optimize ARV treatment in resource-limited settings.
Stand-Alone TAF for Treatment-Experienced Patients
Also of great potential is TAF’s utility for treatment-experienced people living with HIV. According to in vitro data presented by Gilead researchers at the June 4–8, 2013, International Workshop on HIV and Hepatitis Virus Drug Resistance Curative Strategies in Toronto, 25 mg TAF leads to an intracellular 95 percent inhibitory quotient (IQ95) that is five times higher than the TDF IQ95, which is sufficient to overcome the K65R RT mutation, the multi-NRTI T69S and Q151M mutations, and other thymidine analog mutation (TAM)–inclusive variants.
TAF is therefore not just a promising alternative to TDF in first-line regimens, it is a candidate for second-line and salvage regimens for individuals who have developed HIV resistance to nucleoside/nucleotide reverse transcriptase inhibitors including, but not limited to, TDF. As many of these individuals likely developed resistance to other ARVs included in current and planned TAF-inclusive FDCs, development of a stand-alone TAF formulation is necessary so that it may be combined with other approved and experimental compounds as needed.
We understand that additional trials will likely be needed to confirm the appropriate dose for use in combination with other ARVs, at a cost that must be borne by Gilead alone. This must include complete pharmacokinetic (PK) evaluations. The TAF-inclusive FDCs currently in development contain cobicistat and there is an established relationship between TAF exposure when used in boosted and unboosted regimens. Without a full assessment of TAF’s Cmin, Cmax, and AUC as they correspond with safety and efficacy in an unboosted regimen, generic manufacturers will be unable to demonstrate bioequivalence of TAF when used without cobicistat or ritonavir.
Given TAF’s potential, however, we believe that the additional market value of combining TAF with multiple other regimens would more than cover the cost of these additional trials, and could have tremendous benefits in both high- and lower-income countries.
We appreciate your time and careful consideration of this request. We hope this letter will be followed by a meeting or teleconference to discuss this matter further. In the meantime, should you have any questions or immediate feedback, please do not hesitate to be in touch.
Tim Horn, Treatment Action Group
Polly Clayden, HIV i-Base
David Evans, Project Inform
Norbert W. Bischofberger, PhD
Executive Vice President, Research and Development
Chief Scientific Officer
Greg H. Alton
Executive Vice President, Corporate and Medical Affairs
293 Signatories as of Jue 24, 2013
Haresh Advani, Thailand
Vikas Ahuja, Delhi Network of Positive People, India
Jose Antonio Alfao Ruiz, Spain
Dirk Alvera, diego62.wordpress.com, germany
Julius Amoako, Young Activists Against Aids, Ghana
Elijah Amooti, The African Eye Trust, UK
Michael Antinucci, U.S.A.
Thomas Approbato, U.S.A.
William Arnold, Comminity Access National Networ - CANN, U.S.A.
Robergt Atkins, Partnership for a Healthier Arlington, U.S.A.
Johann Averbeck Krammer, Germany
ANGEL AYALA GONZALEZ, SPAIN
Karen Barnes, University of Cape Town, South Africa
Jody Barnofsky, U.S.A.
Sean Barry, Voices Of Community Leaders & Activists (VOCAL-NY), U.S.A.
Donald Bean, MD, U.S.A.
Timothy Beauchamp, Member of Open Table Untied Church of Christ Owasso, Oklahoma, U.S.A.
David Becker, U.S.A.
Paul Curtis Bellman M.D. P. C. , U.S.A.
Jeff Berry, Test Positive Aware Network, U.S.A.
Damir Bikmukhametov, AIDS Healthcare Foundation, Russia
Janhuib Blans, Netherland
Corinne Blum, U.S.A.
Kamil Borowik, U.S.A.
Chureeratana Bowonwatanuwong, Chonburi Hospital, Thailand
Peter Boxill, Germany
Wanda Brendle-Moss, Living with AIDS, U.S.A.
Garry Brough, Bloomsbury Patients Network, United Kingdom
Reginald Brown, Unity Fellowship Church NYC, U.S.A.
Matthias Caba, Germany
Pere Calvo, spain
Robert Cameron, U.S.A.
Rob Camp, Spain
Jaya Canterbury-Counts, Riverfund, Inc., U.S.A.
Jorge Cao, spain
Richard Cardillo, U.S.A.
Darry Carlstone, U.S.A.
Joan Centelles, none, Spain
Alessandra Cerioli, LILA Italian League for Fighting Aids, Italy
Brenda Chambers, U.S.A.
Matt Chappell LCSW, U.S.A.
Enrique Chavez, AID FOR AIDS, Latin America
Daniel Chiarilli, Gay Health Advocacy Project, Columbia University Health Service, U.S.A.
Jerry Clark, U.S.A.
Paul Clift, England
Ben Collins, International HIV Partnerships, UK
Chris Collins, amfAR, the Foundation for AIDS Research, U.S.A.
Simon Collins, HIV i-Base, United Kingdom
Wanda Commander, Lifelinc of MD, U.S.A.
Giulio Maria Corbelli, Italy
Mark Cotton, Stellenbosch University, South Africa
Ben Cromarty, North Yorkshire AIDS Action, United Kingdom
William Curran, U.S.A.
john cutz, U.S.A.
Peter Daley, Memorial University, Canada
arianne dar, U.S.A.
vijay Dasari, U.S.A.
Kendrick Davis, U.S.A.
Peter Davis, U.S.A.
Jose de Marco, ACT UP Philadelphia, U.S.A.
Paul Decle, Forum Link, Engaland
Nikos Dedes, Positive Voice, Greece
Michael Deighan, Nightsweats & T-cell,s Co., U.S.A.
Alex Delgado, U.S.A.
Margaret Denison, Health Education Network, U.S.A.
Terry Dennison, U.S.A.
Penny DeNoble, U.S.A.
Philip Dickey, U.S.A.
Joseph Joey Dluzak, Ordained Minister, U.S.A.
Jolene Donatelli, CTAC, Canada
Michael Dorosh, Treatment Eduat10n Network, U.S.A.
John Drohan, U.S.A.
Vuyiseka Dubula, Treatment Action Campaign, South Africa
James Dunn, Member CAB, San Diego
Saswata Dutt, Institute of Human Virology, Nigeria, Nigeria
Benjamin Dzivenu, Hope Care Foundation, Ghana
Raymond Egolf, U.S.A.
Cordula Ehlers, Take That TB, Germany
Jim Eigo, U.S.A.
Max Erickson, U.S.A.
Adam Fairbanks, U.S.A.
Robert Ferguson, U.S.A.
JosÈ Fern·ndez, Spain
Robert Fieldhouse, BASELINE Magazine, United Kingdom
Paul Fitzgerald, AIDS Care Ocean State, U.S.A.
Natalie Flath, U.S.A.
Xavier Franquet, Spanish HIV Community Advisory Board (FEAT) and European AIDS Treatment Group (EATG), Catalonia/Spain
Jennifer Furin, U.S.A.
Andrew Fyne, Marin AIDS Project, U.S.A.
Jeff Gamel , U.S.A.
COULIBALY Gaoussou, Stop Tuberculosis BOUAKE, CÙte d'Ivoire
Margie Garber-Steinberg, U.S.A.
Diego GarcÌa Morcillo, ADHARA, Spain
Diego GarcÌa Morcillo, FEAT, Spain
Nathan Geffen, Centre for Social Science Research, UCT, South Africa
Benjamin Gerritz, U.S.A.
Denis Godlevskiy, AIDS Healthcare Foundation, Russia
Gorka Goitiz, Spain
Sergey Golovin, International Treatment Preparedness Coalition, Russia
Andriy Gorobets, All-Ukrainian Network of PLWH Krivoy Rog, Ukraine
James Gouldmann, U.S.A.
Massimo Greco, Italy
Maurice Greenham, UK
Howard Grossman, MD, U.S.A.
Etienne Guillard, France
Anthony Guillaume, U.S.A.
Alejandro GuillÈn, Spain
David Hamburger, U.S.A.
Gary Hammond, UK
David Hardy, MD, U.S.A.
Jason Harper, United Kingdom
Patrick Hazelton, UCSF - Center for AIDS Prevention Studies, U.S.A.
Kenneth Henderson, The Richmond/Ermet AIDS Foundation, USA
Brad Hepburn, United Kingdom
Roberto Hermida, AsociaciÛn T4 de lucha contra el Sida, Spain
rafael hernandex, espaÒa
ANGEL HERNANDEZ, Puerto Rico
Juanse Hernandez, Grupo de Trabajo sobre Tratamientos del VIH (gTt-VIH), Spain
Raymond Hilerio, U.S.A.
Francis Hill, USA
David Holland, Duke University, United States
Oliver Horn, Germany
Tina Hylton-Kong, Jamaica
D L:eo-Thiha Ike, U.S.A.
Petros Isaakidis, MÈdecins Sans Frontieres, India
Edward Iwanicki, U.S.A.
Raul Jimenez Martinez, Spain
David Johnson, U.S.A.
Loren Jones, Positive Women's Network-united states of america, usa
Rebecca Jordan-Young, Barnard College, Columbia University (for identification only), USA
Maxime Journiac, EATG, France
Rose kaberia, ITPC-EA, Kenya
Gbemuotor Kama, Professionals For Humanity (PROFOH), Germany
Sharon Kathrens, U.S.A.
James Clovis KAYO, ITPC Central Africa, Cameroun
Andy Kaytes, Drug Development Committee of the AIDS Treatment Activists Coalition, U.S.A.
John Keller, United Kingdom
Bruce Kellerhouse, Ph.D., U.S.A.
Chad Kenney, PWA Coalition Colorado, USA
Tatyana Khan, ITPCru, Ukraine
Bactrin Killingo, ITPC, Kenya
Vincent Konetsky, U.S.A.
Marcin Koziol, Germany
Kate Krauss, AIDS Policy Project, U.S.A.
Tapiwanashe Kujinga, Pan-African Treatment Access Movement, Zimbabwe
Volodymyr Kurpita, Ukraine
JOSEPH KWASHIE, COMMUNITY AND FAMILY AID FOUNDATION (GHANA), Ghana
Charles Lacombe, U.S.A.
Kristen Lamberjack, U.S.A.
Fredric Larsson-Prive', Thailand
Jack Lewis, South Africa
Tobias Linke, Germany
Gabrielle Linton, U.S.A.
Annette Lizzul, U.S.A.
Richard Loftus, M.D., Eisenhower Medical Center, U.S.A.
Edward Low, Positive Malaysian Treatment Access & Advocacy Group (MTAAG+), Malaysia
George Lowe, U.S.A.
Michael Luciano, MUSC/Lowcountry AIDS Svces Consumer Advisory Board, U.S.A.
Gomer weko Lulendo, Botswana
Alan Timothy Lunceford - Stevens, End AIDS Now, U.S.A., France, Denmark
Larry Lyle, Larry N Lyle, DO, U.S.A.
curtis lyles, usa
Gary Maartens, South Africa
Alby Maccarone, Treatment Action Group, U.S.A.
Derrick Mapp, U.S.A.
Michael Marco, Dept. of Epidemioloy, Columbia University School of Public Health, U.S.A.
Simone Marcotullio, Nadir Onlus, Italy
sergio t marecha, mozambique
aranjuelo san sebastian maria isabel, espaÒa
Michael Marr, Waverley Care & UKCAB, Scotland-UK
Cipriana MartÌn, Spain
Juan Alejandro Martinez Palafox, Mexico
Dr. Joshua Matacotta, U.S.A.
Dabu Mayanglambam, Community Network for Empowerment (CoNE), India
John J. McCarthy, U.S.A.
Robert McCormick, U.S.A.
Stephen McGILL, Stop AIDs in Liberia (SAIL), Liberia
Helen McIlleron, University of Cape Town, South Africa
Lindsay McKenna, Treatment Action Group, U.S.A.
Abou Mere, Indian Drug User's Forum, India
Michael Meulbroek, Projecte dels NOMS-Hispanosida, Spain
mark meyer, U.S.A.
Barbra Minch, William F. Ryan Community Health Network, U.S.A.
Lonely Mlumbe, ght, Malawi
SUBRAT MOHANTY, The Union, India
Herman Morales, Cornell Clinical Trails Unit C.A.B.member, U.S.A.
STEVE MORITZ, U.S.A.
Absalom moyo, south africa
Steven Muchnick, PhD, U.S.A.
Jose Joaquin Mulinelli-Rodriguez, Coai, Inc., U.S.A.
David Ernesto Munar, AIDS Foundation of Chicago, U.S.A.
Robert Munk, U.S.A.
salim mustafa, dissabled HIV positives, kenya
Christopher Nettles, The George Washington University, U.S.A.
Kim Nichols, African Services Committee, U.S.A.
Mark Niedzolkowski, New York Buyer's Club, U.S.A.
Alessandra Nilo, LACCASO, LAC
Edward Nizolek,Jr., U.S.A.
Jean Pierre NJOCK, I-CHANGE (International Centre for Humanitarian Action, Networking and Grassroots Empowerment), Cameroon
kennedy olango, MEN AGAINST AIDS YOUTH GROUP, Kenya
Bjorn Olson, Architect, U.S.A.
Godwyns Onwuchekwa, UK
Nelson Otwoma, NEPHAK, Kenya
agata pacho, UK
DEAN PAGE, U.S.A.
Bijay Pandey, ANPUD, Nepal
Manoj Pardeshi, NATIONAL COALITION OF PLHIV IN INDIA (NCPI+), india
Ron Parisi, U.S.A.
Roger Pebody, NAM, UK
Philip Penrose, Canada
Silvia Petretti, Positively UK, United Kingdom
REX PILGRIM, Australia
Coalition PLUS, International
Roy J. Puciato, U.S.A.
Lee Raines, U.S.A.
SANJAY RATHOD, sairam health care charitable trust, India
Thomas Reed, U.S.A.
Robert Reinhard, U.S.A.
Luke Reiser, Marin AIDS Project, U.S.A.
Chris Ritter, U.S.A.
Denisse Rivera , U.S.A.
Daniel Robison, Being Alive, U.S.A.
Sherry Rodio, U.S.A.
jose alexis rodriguez sanchez, spain
RONALD ROSENES, Ron Rosenes Consulting, Canada
Guffran Rostom, Mauritius
Alberto Rubio, U.S.A.
Asia Russell, Health GAP, U.S.A.
Memory Sachikonye, UKCAB, UK
Shona Schonning, belgium
John Schuster, U.S.A.
Evan Schwartz, U.S.A.
gerry scoppettuolo, ACT UP BOSTON, U.S.A.
Sam See, Yale University, U.S.A.
Frank Selvaggi, U.S.A.
Waheedah Shabazz-El, Positive Women's Network-USA -Phila, U.S.A.
Ramya Sheshadri, India
Ed Sikov, U.S.A.
KENLY SIKWESE, AFROCAB, Zambia
samuel silling, U.S.A.
sue simon, U.S.A.
Theo Smart, Treatment Science Writers (treatmentsciencewriters.com), U.S.A./South Africa
Debi Ann Smith Harvey, poz.com, firstname.lastname@example.org, Isle of Man
Igor Sobolev, Estonia
Ontshabetse Arnold Imaan Sokwa, Fight Crime In Botswana, Botswana,Southern Africa.
Nathan Solomon, U.S.A.
Jose Sousa, Canada
Peter Staley, U.S.A.
Quintin Stroud, U.S.A.
Suzy Subways, Prison Health News, U.S.A.
Paul Sutton, CTAC (Canadian Treatment Action Council), Canada
Tracy Swan, Treatment Action Group, U.S.A.
Joan Tallada, Spain
Stuart Tan, singapore
Jeff Taylor, AIDS Treatment Activists Coalition, U.S.A.
Chloe Thio, Johns Hopkins University, U.S.A.
Audrey Thom, Private, South Africa
Stephanie Topp, Centre for Infectious Disease Research in Zambia, Zambia
Elizabeth Tracey, Cleveland State University, U.S.A.
Roy Trevelion, UK
Jerry Turner, U.S.A.
Pilar ustero, swaziland
Ricardo Valtuena, Spain
Carole Vance, Columbia University Mailman Sch Pub Health, U.S.A.
Wim Vandevelde, TB CAB, South Africa
Ricardo Vargas, U.S.A.
Telmo Vasquez, U.S.A.
Andrew Velez, ACT UP New York-, U.S.A.
JC Vera, U.S.A.
Giovanni Vitacolonna, U.S.A.
Jay Vithalani, U.S.A.
filippo von schloesser, NADIR - EATG, Italy
Marc Wagner, U.S.A.
Mark Walter, U.S.A.
Lee Waters, U.S.A.
James Weihe, U.S.A.
Tendayi Westerhof, Women's Health, HIV and AIDS Southern Africa, Zimbabwe
Tod Weymouth, U.S.A.
Laura Whitehorn, U.S.A.
Matthias Wienold, Germany
Christopher Williams, UK
Forrest Williams, U.S.A.
Matt Williams, UK
b willis, U.S.A.
Michael Willis, U.S.A.
Will Wilson, U.S.A.
Mark Woodcock, U.S.A.
clinton woods, Mr., U.S.A.
George Worthington, World Foundation for Medical Research and Prevention, U.S.A.
Mark Wyn, U.S.A.
Abdullahi Yakubu, TB & Leprosy Control Programme, Nigeria
Anna Zakowicz, GNP+, Poland
Paul Zeitz, Endgame, U.S.A.
Eisenberg EJ, He GX, Lee WA. Metabolism of GS-7340, a novel phenyl monophosphoramidate intracellular prodrug of PMPA, in blood. Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):1091–8. doi: 10.1081/NCN-100002496. http://www.ncbi.nlm.nih.gov/pubmed/11562963.
Zolopa A, DeJesus E, D Berger D, et al. Comparative study of tenofovir alafenamide vs. tenofovir disoproxil fumarate, each with elvitegravir, cobicistat, and emtricitabine, for HIV treatment (Abstract 99LB). Paper presented at: 20th Conference on Retroviruses and Opportunistic Infections; 2013 March 3–6; Atlanta, GA. http://www.retroconference.org/2013b/Abstracts/47979.htm.
Buscher A, Hartman C, Kallen MA, Giordano TP. Impact of antiretroviral dosing frequency and pill burden on adherence among newly diagnosed, antiretroviral-naïve HIV patients. Int J STD AIDS. 2012 May;23(5):351–5. doi: 10.1258/ijsa.2011.011292.
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Washington, D.C.: Department of Health and Human Services; 2013 March. Available from: http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf.
Walensky RP, Sax PE, Nakamura YM, et al. The clinical and economic impact of a generic first-line antiretroviral regimen in the U.S. (Abstract FRLBX06). Paper presented at: 19th International AIDS Conference; 2012 July 22–27; Washington, D.C. Available from: http://pag.aids2012.org/abstracts.aspx?aid=21075.
World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, 2013 (forthcoming).
Clinton Health Access Initiative. Antiretroviral (ARV) ceiling price list. New York: Clinton Health Access Initiative; 2013 May. Available from: http://www.clintonhealthaccess.org/files/CHAI_ARV_Ceiling_Price_List_May_2013.pdf.
Margot N, Lui Y, Babusis D, et al. Antiviral activity of tenofovir alafenamide (TAF) against major NRTI-resistant viruses: improvement over TDF/TFV is driven by higher TFV-DP loading in target cells (Abstract 23). Paper presented at: International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies; 2013 June 4–8, Toronto. Available from: http://i-base.info/higher-intracellular-concentrations-with-tenofovir-alafenamide-taf-overcomes-k65r-and-other-key-nrti-resistance-in-vitro/