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1

Gibson, Amanda K., Bhavik M. Shah, Puja H. Nambiar, and Jason J. Schafer. "Tenofovir Alafenamide." Annals of Pharmacotherapy 50, no. 11 (July 28, 2016): 942–52. http://dx.doi.org/10.1177/1060028016660812.

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2

Mothobi, Nomvuyo Z., Jeffrey Masters, and Deborah J. Marriott. "Fanconi syndrome due to tenofovir disoproxil fumarate reversed by switching to tenofovir alafenamide fumarate in an HIV-infected patient." Therapeutic Advances in Infectious Disease 5, no. 5 (July 10, 2018): 91–95. http://dx.doi.org/10.1177/2049936118785497.

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A case of tenofovir-induced Fanconi syndrome in a patient receiving antiretroviral therapy for HIV infection, with resolution of the related electrolyte abnormalities upon switch from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate, is reported. Tenofovir alafenamide fumarate, a novel prodrug of tenofovir containing significantly lower doses of tenofovir than tenofovir disoproxil fumarate, has been associated with a favourable renal profile compared to tenofovir disoproxil fumarate. Generally, the rare complication of tenofovir disoproxil fumarate–induced Fanconi syndrome is managed by cessation of tenofovir. There are limited reports of the impact of a switch strategy from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate, which may be necessary in patients unable to discontinue tenofovir.
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3

Lengauer, Hannes, Damjan Makuc, Damjan Šterk, Franc Perdih, Arthur Pichler, Tina Trdan Lušin, Janez Plavec, and Zdenko Časar. "Co-crystals, Salts or Mixtures of Both? The Case of Tenofovir Alafenamide Fumarates." Pharmaceutics 12, no. 4 (April 10, 2020): 342. http://dx.doi.org/10.3390/pharmaceutics12040342.

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Tenofovir alafenamide fumarate (TAF) is the newest prodrug of tenofovir that constitutes several drug products used for the treatment of HIV/AIDS. Although the solid-state properties of its predecessor tenofovir disoproxil fumarate have been investigated and described in the literature, there are no data in the scientific literature on the solid state properties of TAF. In our report, we describe the preparation of two novel polymorphs II and III of tenofovir alafenamide monofumarate (TA MF2 and TA MF3). The solid-state structure of these compounds was investigated in parallel to the previously known tenofovir alafenamide monofumarate form I (TA MF1) and tenofovir alafenamide hemifumarate (TA HF). Interestingly, the single-crystal X-ray diffraction of TA HF revealed that this derivative exists as a co-crystal form. In addition, we prepared a crystalline tenofovir alafenamide free base (TA) and its hydrochloride salt (TA HCl), which enabled us to determine the structure of TA MF derivatives using 15N-ssNMR (15N-solid state nuclear magnetic resonance). Surprisingly, we observed that TA MF1 exists as a mixed ionization state complex or pure salt, while TA MF2 and TA MF3 can be obtained as pure co-crystal forms.
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4

Wassner, Chanie, Nicole Bradley, and Yuman Lee. "A Review and Clinical Understanding of Tenofovir: Tenofovir Disoproxil Fumarate versus Tenofovir Alafenamide." Journal of the International Association of Providers of AIDS Care (JIAPAC) 19 (January 1, 2020): 232595822091923. http://dx.doi.org/10.1177/2325958220919231.

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HIV is a serious chronic medical condition. Significant improvements in antiretroviral therapy have led to a transformation in its management. No curative treatment is available for HIV, and lifelong therapy is required with a combination of agents to control viral replication and prevent complications. Some of the older agents are notorious for many side effects, making patient compliance difficult, which is critical to preventing HIV resistance. Tenofovir is one of the newer, more tolerable, nucleotide reverse transcriptase inhibitors on the market; is a mainstay of many antiretroviral therapy combinations; and is now available in 2 different formulations, tenofovir disoproxil fumarate (TDF) and, the more recent, tenofovir alafenamide (TAF). These 2 formulations have very different pharmacokinetics, which seem to affect their efficacy and safety. This manuscript provides insight into the history of TDF and TAF development, their unique pharmacokinetics and pharmacology, clinically important adverse effects, monitoring, interactions, resistance, review of clinical studies, and guideline recommendations and clinical applications for tenofovir’s various indications.
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5

Álvarez, Hortensia, and Josep M. Llibre. "Fanconi Syndrome and Tenofovir Alafenamide." Annals of Internal Medicine 171, no. 8 (October 15, 2019): 598. http://dx.doi.org/10.7326/l19-0476.

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6

Bahr, Nathan C., and Sri G. Yarlagadda. "Fanconi Syndrome and Tenofovir Alafenamide." Annals of Internal Medicine 171, no. 8 (October 15, 2019): 599. http://dx.doi.org/10.7326/l19-0477.

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7

Khawaja, Akif A., Kirk A. Taylor, Andrew O. Lovell, Mark Nelson, Brian Gazzard, Marta Boffito, and Michael Emerson. "HIV Antivirals Affect Endothelial Activation and Endothelial-Platelet Crosstalk." Circulation Research 127, no. 11 (November 6, 2020): 1365–80. http://dx.doi.org/10.1161/circresaha.119.316477.

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Rationale: People living with HIV on effective antiretroviral therapy are at increased risk of cardiovascular complications, possibly due to off-target drug effects. Some studies have associated antiretroviral therapy with increased risk of myocardial infarction and endothelial dysfunction, but a link between endothelial function and antiretrovirals has not been established. Objective: To determine the effects of antiretrovirals in common clinical use upon in vitro endothelial function to better understand cardiovascular risk in people living with HIV. Methods and Results: Human umbilical cord vein endothelial cells or human coronary artery endothelial cells were pretreated with the antiretrovirals abacavir sulphate (ABC), tenofovir disoproxil fumarate, or tenofovir alafenamide. Expression of adhesion molecules, ectonucleotidases (CD39 and CD73), tissue factor (TF), endothelial-derived microparticle (EMP) numbers and phenotype, and platelet activation were evaluated by flow cytometry. TF and ectonucleotidase activities were measured using colourimetric plate-based assays. ABC-treated endothelial cells had higher levels of ICAM (intercellular adhesion molecule)-1 and TF expression following TNF (tumor necrosis factor)-α stimulation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide treatment gave rise to greater populations of CD39 + CD73 + cells. These cell surface differences were also observed within EMP repertoires. ABC-treated cells and EMP had greater TF activity, while tenofovir disoproxil fumarate- and tenofovir alafenamide-treated cells and EMP displayed higher ectonucleotidase activity. Finally, EMP isolated from ABC-treated cells enhanced collagen-evoked platelet integrin activation and α-granule release. Conclusions: We report differential effects of antiretrovirals used in the treatment of HIV upon endothelial function. ABC treatment led to an inflammatory, prothrombotic endothelial phenotype that promoted platelet activation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide conferred potentially cardioprotective properties associated with ectonucleotidase activity. These observations establish a link between antiretrovirals and specific functional effects that provide insight into cardiovascular disease in people living with HIV.
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8

Biagi, MJ, CA Schriever, TD Chiampas, SM Michienzi, MC Patel, JD Young, and ME Badowski. "Development of gynecomastia following initiation of bictegravir/emtricitabine/tenofovir alafenamide." International Journal of STD & AIDS 31, no. 4 (February 10, 2020): 380–82. http://dx.doi.org/10.1177/0956462419895665.

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Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is a recently approved single-tablet antiretroviral regimen and is recommended as a first-line agent. No cases of gynecomastia were reported in clinical trials. We report development of ultrasound-confirmed gynecomastia in a previously antiretroviral-naïve patient approximately two months after starting BIC/FTC/TAF, which resolved ten weeks after discontinuing bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) based therapy.
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9

Yamada, Hiroyuki, Takuma Yonemura, Takanori Nemoto, Noriko Ninomiya, and Shin Irie. "Pharmacokinetics of Tenofovir Alafenamide, Tenofovir, and Emtricitabine Following Administration of Coformulated Emtricitabine/Tenofovir Alafenamide in Healthy Japanese Subjects." Clinical Pharmacology in Drug Development 8, no. 4 (October 16, 2018): 511–20. http://dx.doi.org/10.1002/cpdd.623.

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10

Satsangi, Sandeep. "To use entecavir, tenofovir disoproxil fumarate or tenofovir alafenamide." European Journal of Gastroenterology & Hepatology 30, no. 6 (June 2018): 689–90. http://dx.doi.org/10.1097/meg.0000000000001104.

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11

Gupta, Samir K., Frank A. Post, José R. Arribas, Joseph J. Eron, David A. Wohl, Amanda E. Clarke, Paul E. Sax, et al. "Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate." AIDS 33, no. 9 (July 2019): 1455–65. http://dx.doi.org/10.1097/qad.0000000000002223.

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12

Brainard, Diana, and Scott McCallister. "Tenofovir Alafenamide for HIV Preexposure Prophylaxis." Annals of Internal Medicine 173, no. 1 (July 7, 2020): 77–78. http://dx.doi.org/10.7326/l20-0300.

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13

Krakower, Douglas S., Demetre C. Daskalakis, Judith Feinberg, and Julia L. Marcus. "Tenofovir Alafenamide for HIV Preexposure Prophylaxis." Annals of Internal Medicine 173, no. 1 (July 7, 2020): 78. http://dx.doi.org/10.7326/l20-0301.

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14

Boyd, Mark A., and David A. Cooper. "Tenofovir alafenamide: safer, but questions remain." Lancet HIV 3, no. 4 (April 2016): e148-e149. http://dx.doi.org/10.1016/s2352-3018(16)00039-4.

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15

Abbasi, Anna Amjad, Ravikaran Patti, Arindam Ghatak, Chanaka Seneviratne, Yizhak Kupfer, and Stephan Kamholz. "Tenofovir Alafenamide-Induced Renal Tubular Acidosis." American Journal of Therapeutics 26, no. 5 (2019): e627-e628. http://dx.doi.org/10.1097/mjt.0000000000000834.

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16

Sax, Paul E., Edwin DeJesus, Gordon Crofoot, Douglas Ward, Paul Benson, Robin Dretler, Anthony Mills, et al. "Coformulated bictegravir, emtricitabine, tenofovir alafenamide after initial treatment with bictegravir or dolutegravir and emtricitabine/tenofovir alafenamide." AIDS 32, no. 12 (July 2018): 1723–25. http://dx.doi.org/10.1097/qad.0000000000001894.

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17

Dhanireddy, Shireesha, and Jared M. Baeten. "Tenofovir alafenamide for HIV: time to switch?" Lancet Infectious Diseases 16, no. 1 (January 2016): 3–5. http://dx.doi.org/10.1016/s1473-3099(15)00412-0.

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18

Hussar, Daniel A., and Rachel C. Boardman. "Bictegravir/emtricitabine/tenofovir alafenamide, Ibalizumab, and Ozenoxacin." Journal of the American Pharmacists Association 58, no. 4 (July 2018): 460–63. http://dx.doi.org/10.1016/j.japh.2018.06.010.

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19

De Clercq, Erik. "Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF)." Biochemical Pharmacology 119 (November 2016): 1–7. http://dx.doi.org/10.1016/j.bcp.2016.04.015.

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20

Jaroszewicz, Jerzy. "The role of tenofovir alafenamide (TAF) in treatment of HBV infection." Zakażenia XXI wieku 2018, no. 2 (June 1, 2018): 67–72. http://dx.doi.org/10.31350/zakazenia/2018/2/zz2018013.

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21

Darnell, Julia, Sonia Jain, Xiaoying Sun, Huifang Qin, Timothy Reynolds, Maile Young Karris, and Lucas A. Hill. "Impact of switching to tenofovir alafenamide on weight gain as compared to maintaining a non-tenofovir alafenamide containing regimen." Medicine 100, no. 34 (August 27, 2021): e27047. http://dx.doi.org/10.1097/md.0000000000027047.

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22

K, Pushpa Kumari, and Gowri Sankar D. "STABILITY INDICATING UPLC METHOD FOR SIMULTANEOUS ESTIMATION OF EMTRICITABINE, BICTEGRAVIR AND TENOFOVIR ALAFENAMIDE." INDIAN DRUGS 57, no. 01 (January 28, 2020): 44–50. http://dx.doi.org/10.53879/id.57.01.11717.

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A simple, specific, precise and robust method for the estimation of emtricitabine, bictegravir and tenofovir alafenamide in the presence of impurities was developed and validated. The separation was performed on Aquity UPLC system with SB C8 50 x 2.1 mm, 1.7μ column under isocratic elution mode. The components were eluted using 0.01 N phosphate buffer and acetonitrile in the ratio of 50:50 V/V and detected at UV wavelength of 272 nm. The retention times were found to be 1.017 min, 1.484 min and 1.864 min for emtricitabine, bictegravir and tenofovir alafenamide, respectively. The developed method was validated as per ICH guidelines. The method was stable and specific and when the sample was stressed under different conditions (acid, base, peroxide, photolytic, neutral, no interference of degradants were observed.
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23

Post, Frank, Paul Sax, Michael Saag, Michael Yin, Shinichi Oka, Ellen Koenig, Benoit Trottier, Jaime Andrade, Huyen Cao, and Marshall Fordyce. "P99 Renal and bone safety of tenofovir alafenamide vs tenofovir disoproxil fumarate." Sexually Transmitted Infections 91, Suppl 1 (May 18, 2015): A48.3—A49. http://dx.doi.org/10.1136/sextrans-2015-052126.142.

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24

Funderburg, Nicholas T., Grace A. McComsey, Manjusha Kulkarni, Tammy Bannerman, Jessica Mantini, Bernadette Thornton, Hui C. Liu, et al. "Equivalent Decline in Inflammation Markers with Tenofovir Disoproxil Fumarate vs. Tenofovir Alafenamide." EBioMedicine 13 (November 2016): 321–27. http://dx.doi.org/10.1016/j.ebiom.2016.10.009.

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25

Michienzi, Sarah M., Mikayla Johnson, Thomas D. Chiampas, Eric Wenzler, Rodrigo M. Burgos, Renata O. Smith, and Melissa E. Badowski. "Real-world impact of switching from tenofovir disoproxil fumarate to tenofovir alafenamide." Drugs in Context 10 (July 21, 2021): 1–6. http://dx.doi.org/10.7573/dic.2021-2-1.

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26

Kumar, Pankaj, Jane Jacob, Khadjeeth Ajina, Jazeela, and Fathima. "Spectroscopic Estimation of Tenofovir Alafenamide, an antiretroviral drug." Research Journal of Pharmacy and Technology 9, no. 5 (2016): 538. http://dx.doi.org/10.5958/0974-360x.2016.00101.3.

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27

Bahr, Nathan C., and Sri G. Yarlagadda. "Fanconi Syndrome and Tenofovir Alafenamide: A Case Report." Annals of Internal Medicine 170, no. 11 (January 29, 2019): 814. http://dx.doi.org/10.7326/l18-0592.

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28

Wyatt, Christina, and Jared M. Baeten. "Tenofovir alafenamide for HIV infection: is less more?" Lancet 385, no. 9987 (June 2015): 2559–60. http://dx.doi.org/10.1016/s0140-6736(15)60725-5.

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29

Brouwer, Willem P. "Tenofovir alafenamide for hepatitis B: evolution or revolution?" Lancet Gastroenterology & Hepatology 1, no. 3 (November 2016): 174–75. http://dx.doi.org/10.1016/s2468-1253(16)30083-8.

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30

"Tenofovir alafenamide." Reactions Weekly 1761, no. 1 (July 2019): 348. http://dx.doi.org/10.1007/s40278-019-64720-1.

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31

"Tenofovir alafenamide." Reactions Weekly 1832, no. 1 (November 2020): 269. http://dx.doi.org/10.1007/s40278-020-86802-0.

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32

"Tenofovir alafenamide." Reactions Weekly 1726, no. 1 (November 2018): 318. http://dx.doi.org/10.1007/s40278-018-53957-6.

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33

"Tenofovir-alafenamide." Reactions Weekly 1834, no. 1 (December 2020): 239. http://dx.doi.org/10.1007/s40278-020-87431-2.

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34

"Tenofovir alafenamide." Reactions Weekly 1699, no. 1 (April 2018): 280. http://dx.doi.org/10.1007/s40278-018-45548-0.

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35

"Tenofovir-alafenamide/tenofovir-disoproxil-fumarate." Reactions Weekly 1699, no. 1 (April 2018): 281. http://dx.doi.org/10.1007/s40278-018-45549-0.

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36

"Tenofovir alafenamide/tenofovir disoproxil fumarate." Reactions Weekly 1868, no. 1 (August 2021): 388. http://dx.doi.org/10.1007/s40278-021-00845-2.

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37

"Tenofovir alafenamide/emtricitabine." Reactions Weekly 1654, no. 1 (June 2017): 324. http://dx.doi.org/10.1007/s40278-017-31057-4.

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38

"Gentamicin/tenofovir alafenamide." Reactions Weekly 1820, no. 1 (September 2020): 143. http://dx.doi.org/10.1007/s40278-020-82963-4.

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39

"Adefovir/tenofovir-alafenamide." Reactions Weekly 1762, no. 1 (July 2019): 20. http://dx.doi.org/10.1007/s40278-019-64759-y.

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40

"Emtricitabine/tenofovir alafenamide." Reactions Weekly 1673, no. 1 (October 2017): 163. http://dx.doi.org/10.1007/s40278-017-37251-8.

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41

Lagoutte-Renosi, Jennifer, Mylène Flammang, Catherine Chirouze, Geneviève BeckWirth, Fabienne Bozon, Anne-Sophie Brunel, Marie-Christine Drobacheff-Thiebaut, et al. "Real-Life Impact on Lipid Profile of a Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected Patients." Current HIV Research 18 (August 24, 2020). http://dx.doi.org/10.2174/1570162x18666200824101838.

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Background: Tenofovir disoproxil fumarate is a prodrug of tenofovir diphosphate that exposes patients to renal toxicity over the long term. Tenofovir alafenamide, a new prodrug, now makes it possible to reduce toxicity, but at the cost of an alteration in lipid profile. There is currently no recommendation for follow-up of lipid profile when switching from tenofovir disoproxil fumarate to tenofovir alafenamide. Objective: Our study aimed to evaluate the effects on renal function and lipid profile of a switch from tenofovir disoproxil fumarate to tenofovir alafenamide, and the consequences for patient management. Methods: Demographic, clinical and biological data was recorded from a retrospective clinical cohort study in real-life, including patients who switched from tenofovir disoproxil fumarate to tenofovir alafenamide. A descriptive analysis of the study population, with comparison of biological parameters using the paired Student t test for paired data was performed. Results: From January 2016 to January 2019, a total of 103 patients were included. There was no significant difference in renal function before vs after the switch in therapy (p=0.29 for creatinine, p=0.30 for phosphoremia). We observed a change in lipid profile, with a significant increase in total cholesterol (p=0.0006), HDL cholesterol (p=0.0055) and triglycerides (p=0.0242). Four patients received lipid-lowering therapy after switching. Conclusion: In patients who switch from tenofovir disoproxil fumarate to tenofovir alafenamide, lipid profile is altered, and may require initiation of lipid-lowering therapy. It seems necessary to monitor lipid parameters after this switch, despite the absence of an official recommendation.
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42

"Dolutegravir/emtricitabine/tenofovir alafenamide." Reactions Weekly 1778, no. 1 (November 2019): 183. http://dx.doi.org/10.1007/s40278-019-70986-z.

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43

"Bictegravir/emtricitabine/tenofovir-alafenamide." Reactions Weekly 1825, no. 1 (October 2020): 65. http://dx.doi.org/10.1007/s40278-020-84305-3.

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44

"Bictegravir/emtricitabine/tenofovir alafenamide." Reactions Weekly 1826, no. 1 (October 2020): 82. http://dx.doi.org/10.1007/s40278-020-84529-x.

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45

"Bictegravir/emtricitabine/tenofovir-alafenamide." Reactions Weekly 1826, no. 1 (October 2020): 83. http://dx.doi.org/10.1007/s40278-020-84530-9.

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46

"Bictegravir/emtricitabine/tenofovir-alafenamide." Reactions Weekly 1828, no. 1 (October 2020): 112. http://dx.doi.org/10.1007/s40278-020-85188-9.

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47

"Bictegravir/emtricitabine/tenofovir-alafenamide." Reactions Weekly 1793, no. 1 (February 2020): 103. http://dx.doi.org/10.1007/s40278-020-75445-y.

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48

"Bictegravir/emtricitabine/tenofovir alafenamide." Reactions Weekly 1799, no. 1 (April 2020): 99. http://dx.doi.org/10.1007/s40278-020-77101-2.

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49

"Bictegravir/emtricitabine/tenofovir-alafenamide." Reactions Weekly 1836, no. 1 (January 2021): 176. http://dx.doi.org/10.1007/s40278-021-87995-7.

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50

"Dolutegravir/emtricitabine/tenofovir-alafenamide." Reactions Weekly 1738, no. 1 (February 2019): 111. http://dx.doi.org/10.1007/s40278-019-57485-9.

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