Current and Future PrEP Medications and Modalities: On-demand, Injectables, and Topicals
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Purpose of Review
Pre-exposure prophylaxis (PrEP) is a potent HIV prevention strategy, but uptake of daily oral PrEP remains low. This review covers PrEP agents currently available and agents and modalities under investigation.
Injectable ARV preparations have high acceptability among users but are likely to require adherence to 8-week interval injections. Topical microbicide gels and vaginal rings have underperformed by intention-to-treat analyses in efficacy studies, at least in large part due to challenges with adherence and/or sustained use. However, daily oral TDF-FTC also underperformed in randomized, placebo-controlled trials compared to expectations and subsequent real-world pragmatic use.
On-demand (2-1-1 dosing strategy for MSM) and injectable PrEP appear to be acceptable among participants in clinical trials. These modalities are particularly compelling alternatives for individuals who either do not want to take a daily medication (both on-demand and injectable) and/or want to take PrEP without a long commitment (on-demand). Emerging modalities such as vaginal films, microneedles, and subdermal implants have numerous advantages but are still in early stages of development.
KeywordsPre-exposure prophylaxis (PrEP) HIV/AIDS On-demand Injectables Microbicide gels Vaginal rings
Matthew R. Beymer was supported by the UCLA Postdoctoral Fellowship Training Program in Global HIV Prevention Research (Currier and Gorbach, PIs); T32MH080634.
Ian W. Holloway and Raphael J. Landovit were supported by the Center for HIV Identification, Prevention, and Treatment (CHIPTS; NIMH grant MH58107) and the UCLA Center for AIDS Research (CFAR; NIAID grant AI028697).
Ian W. Holloway was supported by California HIV/AIDS Research Program (CHRP; grant RP15-LA-007) and the National Center for Advancing Translational Sciences through UCLA (CSTI; grant UL1TR000124). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH.
Compliance with Ethics Guidelines
Conflict of Interest
Matthew R. Beymer, Ian W. Holloway and Craig Pulsipher declare that they have no conflict of interest.
Raphael J. Landovit has received research grants from, and served as a consultant to Gilead Sciences; and served as a consultant to Merck and Co, Inc.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.Anderson PL, Glidden DV, Liu A, Buchbinder S, Lama JR, Guanira JV, et al. Emtricitabine-Tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012;4(151):151ra125. https://doi.org/10.1126/scitranslmed.3004006.CrossRefPubMedPubMedCentralGoogle Scholar
- 3.United States Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States. 2014. https://www.cdc.gov/hiv/pdf/prepguidelines2014.pdf. Accessed January 26, 2017 2017.
- 4.• Hosek SG, Landovitz RJ, Kapogiannis B, Siberry GK, Rudy B, Rutledge B, et al. Safety and feasibility of antiretroviral Preexposure prophylaxis for adolescent men who have sex with men aged 15 to 17 years in the United States. JAMA Pediatr. 2017;171(11):1063–71. https://doi.org/10.1001/jamapediatrics.2017.2007. This study was responsible for expanding the TDF/FTC PrEP indication down to include youth (weight of 35 kg or more) by the U.S. Food and Drug Administration.
- 5.AIDS Vaccine Advocacy Coalition (AVAC). Regulatory status of Truvada for PrEP. 2019.Google Scholar
- 6.Smith DK, Van Handel M, Huggins R. Estimated coverage to address financial barriers to HIV Preexposure prophylaxis among persons with indications for its use, United States, 2015. J Acquir Immune Defic Syndr. 2017;76(5):465–72. https://doi.org/10.1097/QAI.0000000000001532.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Gandhi M, Glidden DV, Mayer K, Schechter M, Buchbinder S, Grinsztejn B, et al. Association of age, baseline kidney function, and medication exposure with declines in creatinine clearance on pre-exposure prophylaxis: an observational cohort study. Lancet HIV. 2016;3(11):e521–e8. https://doi.org/10.1016/S2352-3018(16)30153-9.
- 10.Solomon MM, Lama JR, Glidden DV, Mulligan K, McMahan V, Liu AY, et al. Changes in renal function associated with oral emtricitabine/tenofovir disoproxil fumarate use for HIV pre-exposure prophylaxis. AIDS. 2014;28(6):851–9. https://doi.org/10.1097/QAD.0000000000000156.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Glidden DV, Mulligan K, McMahan V, Anderson PL, Guanira J, Chariyalertsak S, et al. Brief report: recovery of bone mineral density after discontinuation of Tenofovir-based HIV pre-exposure prophylaxis. J Acquir Immune Defic Syndr. 2017;76(2):177–82. https://doi.org/10.1097/QAI.0000000000001475.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Marcus JL, Hurley LB, Hare CB, Nguyen DP, Phengrasamy T, Silverberg MJ, et al. Preexposure prophylaxis for HIV prevention in a large integrated health care system: adherence, renal safety, and discontinuation. J Acquir Immune Defic Syndr. 2016;73(5):540–6. https://doi.org/10.1097/QAI.0000000000001129.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Institute of Medicine (US) Committee on a Comprehensive Review of the HHS Office of Family Planning Title X Program; Stith Butler A, Wright Clayton E, editors. A Review of the HHS Family Planning Program: Mission, Management, and Measurement of Results. Washington (DC): National Academies Press (US); 2009. 2, Overview of Family Planning in the United States. Available from: https://www.ncbi.nlm.nih.gov/books/NBK215219/.
- 14.• Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, et al. On-demand Preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015;373(23):2237–46. https://doi.org/10.1056/NEJMoa1506273. This was the first study to show that on-demand PrEP (2-1-1 dosing strategy for MSM) is efficacious for preventing HIV among MSM.
- 15.Antoni G, Tremblay C, Charreau I, Cua E, Rojas-Castro D, Hall N, et al. On-demand PrEP with TDF/FTC remains highly effective among MSM with infrequent sexual intercourse: a sub-study of the ANRS IPERGAY trial. Paris: International AIDS Society; 2017.Google Scholar
- 16.Molina JM, Charreau I, Spire B, Cotte L, Chas J, Capitant C, et al. Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study. Lancet HIV. 2017;4(9):e402–e10. https://doi.org/10.1016/S2352.3018(17)30089-9.
- 18.Cottrell ML, Yang KH, Prince HM, Sykes C, White N, Malone S, et al. A translational pharmacology approach to predicting outcomes of Preexposure prophylaxis against HIV in men and women using Tenofovir Disoproxil fumarate with or without Emtricitabine. J Infect Dis. 2016;214(1):55–64. https://doi.org/10.1093/infdis/jiw077.CrossRefPubMedPubMedCentralGoogle Scholar
- 19.United States Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States - 2017 Update. 2017. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf.
- 20.Grant RM, Mannheimer S, Hughes JP, Hirsch-Moverman Y, Loquere A, Chitwarakorn A, et al. Daily and nondaily Oral Preexposure prophylaxis in men and transgender women who have sex with men: the human immunodeficiency virus prevention trials network 067/ADAPT study. Clin Infect Dis. 2018;66(11):1712–21. https://doi.org/10.1093/cid/cix1086.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Bekker LG, Roux S, Sebastien E, Yola N, Amico KR, Hughes JP, et al. Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town trial): a randomised, open-label, phase 2 trial. Lancet HIV. 2018;5(2):e68–78. https://doi.org/10.1016/S2352-3018(17)30156-X.CrossRefPubMedGoogle Scholar
- 22.Parsons JT, Rendina HJ, Grov C, Ventuneac A, Mustanski B. Accuracy of highly sexually active gay and bisexual men's predictions of their daily likelihood of anal sex and its relevance for intermittent event-driven HIV pre-exposure prophylaxis. J Acquir Immune Defic Syndr. 2015;68(4):449–55. https://doi.org/10.1097/QAI.0000000000000507.CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Massud I, Mitchell J, Babusis D, Deyounks F, Ray AS, Rooney JF, et al. Chemoprophylaxis with Oral Emtricitabine and Tenofovir Alafenamide combination protects macaques from rectal simian/human immunodeficiency virus infection. J Infect Dis. 2016;214(7):1058–62. https://doi.org/10.1093/infdis/jiw312.CrossRefPubMedGoogle Scholar
- 24.Massud I, Cong ME, Ruone S, Mitchell J, Deyounks F, Holder A et al. Oral FTC/TAF Combination Prevents Vaginal SHIV Infection in Pigtail Macaques. Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts; 2018.Google Scholar
- 25.Cottrell ML, Garrett KL, Prince HMA, Sykes C, Schauer A, Emerson CW, et al. Single-dose pharmacokinetics of tenofovir alafenamide and its active metabolite in the mucosal tissues. J Antimicrob Chemother. 2017;72(6):1731–40. https://doi.org/10.1093/jac/dkx064.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Hare CB, Coll J, Ruane P, Molina J, Mayer KH, Jessen H, et al. The Phase 3 Discover Study: Daily F/TAF Or F/TDF For HIV Preexposure Prophylaxis. Conference on Retroviruses and Opportunistic Infections; Seattle, Washington; 2019.Google Scholar
- 28.McGowan I, Dezzutti CS, Siegel A, Engstrom J, Nikiforov A, Duffill K, et al. Long-acting rilpivirine as potential pre-exposure prophylaxis for HIV-1 prevention (the MWRI-01 study): an open-label, phase 1, compartmental, pharmacokinetic and pharmacodynamic assessment. Lancet HIV. 2016;3(12):e569–e78. https://doi.org/10.1016/S2352-3018(16)30113-8.CrossRefPubMedGoogle Scholar
- 29.Jackson AG, Else LJ, Mesquita PM, Egan D, Back DJ, Karolia Z, et al. A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV-negative volunteers for pre-exposure prophylaxis. Clin Pharmacol Ther. 2014;96(3):314-23. https://doi.org/10.1038/clpt.2014.118.CrossRefPubMedGoogle Scholar
- 30.Walensky RP, Jacobsen MM, Bekker LG, Parker RA, Wood R, Resch SC, et al. Potential clinical and economic value of long-acting Preexposure prophylaxis for south African women at high-risk for HIV infection. J Infect Dis. 2016;213(10):1523–31. https://doi.org/10.1093/infdis/jiv523.CrossRefPubMedGoogle Scholar
- 31.Bekker LG, Li SS, Tolley B, Marzinke M, Mgodi NM, Justman J et al. HPTN 076: TMC278 LA Safe, Tolerable, and Acceptable for HIV Preexposure Prophylaxis. Conference on Retroviruses and Opportunistic Infections; Seattle, Washington; 2017.Google Scholar
- 32.Sista N, Li SS, Marzinke M, Mgodi NM, Justman J, Swaminathan S, et al. HPTN 076: safety and pharmacokinetics of rilpivirine LA through week 76 in HIV-uninfected women. Paris, France: International AIDS Society; 2017.Google Scholar
- 35.Dobard C, Makarova N, Nishiura K, Sterling M, Dinh C, Mitchell J et al. Long-Acting Cabotegravir Protects Macaques against Repeated Penile SHIV Exposures. Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts; 2018.Google Scholar
- 37.Spreen W, Ford SL, Chen S, Wilfret D, Margolis D, Gould E, et al. GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects. J Acquir Immune Defic Syndr. 2014;67(5):481–6. https://doi.org/10.1097/QAI.0000000000000301.CrossRefPubMedGoogle Scholar
- 38.Spreen W, Williams P, Margolis D, Ford SL, Crauwels H, Lou Y, et al. Pharmacokinetics, safety, and tolerability with repeat doses of GSK1265744 and rilpivirine (TMC278) long-acting nanosuspensions in healthy adults. J Acquir Immune Defic Syndr. 2014;67(5):487–92. https://doi.org/10.1097/QAI.0000000000000365.CrossRefPubMedGoogle Scholar
- 39.Meyers K, Rodriguez K, Brill AL, Wu Y, La Mar M, Dunbar D, et al. Lessons for patient education around long-acting injectable PrEP: findings from a mixed-method study of phase II trial participants. AIDS Behav. 2018;22(4):1209–16. https://doi.org/10.1007/s10461-017-1871-x.CrossRefPubMedPubMedCentralGoogle Scholar
- 40.Markowitz M, Frank I, Grant RM, Mayer KH, Elion R, Goldstein D, et al. Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial. Lancet HIV. 2017;4(8):e331–e40. https://doi.org/10.1016/S2352-3018(17)30068-1.CrossRefPubMedGoogle Scholar
- 41.• Landovitz R, Li S, Grinsztejn B, Dawood H, Liu A, Magnus M, et al. Safety, tolerability and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected women and men: HPTN 077. Paris, France: International AIDS Society; 2017. This study showed that injectable cabotegravir as PrEP administered every eight weeks met pharmocokinetic targets and was well tolerated.Google Scholar
- 43.Parikh UM, Dobard C, Sharma S, Cong ME, Jia H, Martin A, et al. Complete protection from repeated vaginal simian-human immunodeficiency virus exposures in macaques by a topical gel containing tenofovir alone or with emtricitabine. J Virol. 2009;83(20):10358–65. https://doi.org/10.1128/JVI.01073-09.CrossRefPubMedPubMedCentralGoogle Scholar
- 44.Mayer KH, Maslankowski LA, Gai F, El-Sadr WM, Justman J, Kwiecien A, et al. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006;20(4):543–51. https://doi.org/10.1097/01.aids.0000210608.70762.c3.CrossRefPubMedGoogle Scholar
- 45.Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010;329(5996):1168–74. https://doi.org/10.1126/science.1193748.CrossRefPubMedPubMedCentralGoogle Scholar
- 46.Rees H D-MS, Lombard C. FACTS 001 Phase III Trial of Pericoital Tenofovir 1% Gel for HIV Prevention in Women. Conference on Retroviruses and Opportunistic Infections; February 23–26, 2015; Seattle, Washington; 2015.Google Scholar
- 49.Carballo-Diéguez A, Balán IC, Brown W, Giguere R, Dolezal C, Leu CS, et al. High levels of adherence to a rectal microbicide gel and to oral pre-exposure prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women. PLoS One. 2017;12(7):e0181607. https://doi.org/10.1371/journal.pone.0181607.CrossRefPubMedPubMedCentralGoogle Scholar
- 51.Chen BA, Panther L, Marzinke MA, Hendrix CW, Hoesley CJ, van der Straten A, et al. Phase 1 safety, pharmacokinetics, and pharmacodynamics of Dapivirine and Maraviroc vaginal rings: a double-blind randomized trial. J Acquir Immune Defic Syndr. 2015;70(3):242–9. https://doi.org/10.1097/QAI.0000000000000702.CrossRefPubMedPubMedCentralGoogle Scholar
- 52.van der Straten A, Panther L, Laborde N, Hoesley CJ, Cheng H, Husnik MJ, et al. Adherence and acceptability of a multidrug vaginal ring for HIV prevention in a phase I study in the United States. AIDS Behav. 2016;20(11):2644–53. https://doi.org/10.1007/s10461-016-1299-8.CrossRefPubMedPubMedCentralGoogle Scholar
- 54.Nel A, Bekker LG, Bukusi E, Hellstrm E, Kotze P, Louw C, et al. Safety, acceptability and adherence of Dapivirine vaginal ring in a microbicide clinical trial conducted in multiple countries in sub-Saharan Africa. PLoS One. 2016;11(3):e0147743. https://doi.org/10.1371/journal.pone.0147743.CrossRefPubMedPubMedCentralGoogle Scholar
- 57.Baeten JM, Palanee T, Mgodi NM, Mayo A, Nel A, Rosenberg Z et al. High Uptake and Reduced HIV-1 Incidence in an Open-Label Trial of the Dapivirine Ring. Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts; 2018.Google Scholar
- 58.Nel A, Van Niekerk N, Van Baelen B, Rosenberg Z. HIV Incidence and Adherence in Dream: An Open-Label Trial of Dapivirine Vaginal Ring. Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts; 2018.Google Scholar
- 59.Derby N, Aravantinou M, Kenney J, Ugaonkar SR, Wesenberg A, Wilk J, et al. An intravaginal ring that releases three antiviral agents and a contraceptive blocks SHIV-RT infection, reduces HSV-2 shedding, and suppresses hormonal cycling in rhesus macaques. Drug Deliv Transl Res. 2017;7(6):840–58. https://doi.org/10.1007/s13346-017-0389-0.CrossRefPubMedPubMedCentralGoogle Scholar
- 60.Smith JM, Moss JA, Srinivasan P, Butkyavichene I, Gunawardana M, Fanter R, et al. Novel multipurpose pod-intravaginal ring for the prevention of HIV, HSV, and unintended pregnancy: pharmacokinetic evaluation in a macaque model. PLoS One. 2017;12(10):e0185946. https://doi.org/10.1371/journal.pone.0185946.CrossRefPubMedPubMedCentralGoogle Scholar
- 61.Akil A, Parniak MA, Dezzuitti CS, Moncla BJ, Cost MR, Li M, et al. Development and characterization of a vaginal film containing Dapivirine, a non- nucleoside reverse transcriptase inhibitor (NNRTI), for prevention of HIV-1 sexual transmission. Drug Deliv Transl Res. 2011;1(3):209–22. https://doi.org/10.1007/s13346-011-0022-6.CrossRefPubMedPubMedCentralGoogle Scholar
- 62.Machado A, Cunha-Reis C, Araujo F, Nunes R, Seabra V, Ferreira D, et al. Development and in vivo safety assessment of tenofovir-loaded nanoparticles-in-film as a novel vaginal microbicide delivery system. Acta Biomater. 2016;44:332–40. https://doi.org/10.1016/j.actbio.2016.08.018.CrossRefPubMedGoogle Scholar
- 64.Bunge KE, Dezzutti CS, Rohan LC, Hendrix CW, Marzinke MA, Richardson-Harman N, et al. A phase 1 trial to assess the safety, acceptability, pharmacokinetics, and pharmacodynamics of a novel Dapivirine vaginal film. J Acquir Immune Defic Syndr. 2016;71(5):498–505. https://doi.org/10.1097/QAI.0000000000000897.CrossRefPubMedPubMedCentralGoogle Scholar
- 66.Bunge KE, Dezzutti CS, Hendrix C, Marzinke MA, Spiegel H, Moncla B et al. Phase I trial to assess safety, PK, and PD of film and gel formulations of Tenofovir. Conference on Retroviruses and Opportunistic Infections; Boston; 2016.Google Scholar
- 67.Robinson JA, Marzinke MA, Fuchs EJ, Bakshi RP, Spiegel HML, Coleman JS, et al. Comparison of the pharmacokinetics and pharmacodynamics of single-dose Tenofovir vaginal film and gel formulation (FAME 05). J Acquir Immune Defic Syndr. 2018;77(2):175–82. https://doi.org/10.1097/QAI.0000000000001587.CrossRefPubMedPubMedCentralGoogle Scholar
- 70.MCCrudden M. Two-step casting of dissolving MN arrays for use in the sustained release of rilpivirine for HIV pre-exposure prophylaxis. Proc. 43rd Annu. Meet. Controlled release Soc; 2016.Google Scholar
- 71.Gunawardana M, Remedios-Chan M, Miller CS, Fanter R, Yang F, Marzinke MA, et al. Pharmacokinetics of long-acting tenofovir alafenamide (GS-7340) subdermal implant for HIV prophylaxis. Antimicrob Agents Chemother. 2015;59(7):3913–9. https://doi.org/10.1128/AAC.00656-15.CrossRefPubMedPubMedCentralGoogle Scholar
- 72.Prathipati PK, Mandal S, Pon G, Vivekanandan R, Destache CJ. Pharmacokinetic and tissue distribution profile of long acting Tenofovir Alafenamide and Elvitegravir loaded nanoparticles in humanized mice model. Pharm Res. 2017;34(12):2749–55. https://doi.org/10.1007/s11095-017-2255-7.CrossRefPubMedPubMedCentralGoogle Scholar
- 73.Gatto G, Girouard N, Brand RM, Johnson LM, Marzinke M, Sudie R et al. Pharmacokinetics of Tenofovir Alafenamide by Subcutaneous Implant for HIV PrEP. Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts; 2018.Google Scholar
- 75.Julg B, Tartaglia LJ, Keele BF, Wagh K, Pegu A, Sok D, et al. Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge. Sci Transl Med. 2017;9(406):eaal1321. https://doi.org/10.1126/scitranslmed.aal1321.CrossRefPubMedPubMedCentralGoogle Scholar
- 76.Rosenberg YJ, Montefiori DC, LaBranche CC, Lewis MG, Sack M, Lees JP, et al. Protection against SHIV challenge by subcutaneous Administration of the Plant-Derived PGT121 broadly neutralizing antibody in macaques. PLoS One. 2016;11(3):e0152760. https://doi.org/10.1371/journal.pone.0152760.CrossRefPubMedPubMedCentralGoogle Scholar
- 78.Ledgerwood JE, Coates EE, Yamshchikov G, Saunders JG, Holman L, Enama ME, et al. Safety, pharmacokinetics and neutralization of the broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. Clin Exp Immunol. 2015;182(3):289–301. https://doi.org/10.1111/cei.12692.CrossRefPubMedPubMedCentralGoogle Scholar
- 79.Mayer KH, Seaton KE, Huang Y, Grunenberg N, Isaacs A, Allen M, et al. Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: results of a phase 1 randomized trial. PLoS Med. 2017;14(11):e1002435. https://doi.org/10.1371/journal.pmed.1002435.CrossRefPubMedPubMedCentralGoogle Scholar
- 80.Gaudinski MR, Coates EE, Houser KV, Chen GL, Yamshchikov G, Saunders JG, et al. Safety and pharmacokinetics of the fc-modified HIV-1 human monoclonal antibody VRC01LS: a phase 1 open-label clinical trial in healthy adults. PLoS Med. 2018;15(1):e1002493. https://doi.org/10.1371/journal.pmed.1002493.CrossRefPubMedPubMedCentralGoogle Scholar
- 81.Tyo KM, Vuong HR, Malik DA, Sims LB, Alatassi H, Duan J, et al. Multipurpose tenofovir disoproxil fumarate electrospun fibers for the prevention of HIV-1 and HSV-2 infections in vitro. Int J Pharm. 2017;531(1):118–33. https://doi.org/10.1016/j.ijpharm.2017.08.061.CrossRefPubMedPubMedCentralGoogle Scholar
- 88.Xiao P, Gumber S, Marzinke M, Date AA, Hoang T, Hanes J et al. Hypo-osmolar Rectal Enema TFV Formulation Prevents SHIV Acquisition. Conference on Retroviruses and Opportunistic Infections; Boston, USA; 2018.Google Scholar
- 90.Schlesinger E, Johengen D, Luecke E, Rothrock G, McGowan I, van der Straten A, et al. A tunable, biodegradable, thin-film polymer device as a long-acting implant delivering Tenofovir Alafenamide fumarate for HIV pre-exposure prophylaxis. Pharm Res. 2016;33(7):1649–56. https://doi.org/10.1007/s11095-016-1904-6.CrossRefPubMedPubMedCentralGoogle Scholar