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Current HIV/AIDS Reports

Erschienen in:

20.06.2019 | The Science of Prevention (JD Stekler and JM Baeten, Section Editors)

Current and Future PrEP Medications and Modalities: On-demand, Injectables, and Topicals

verfasst von: Matthew R. Beymer, Ian W. Holloway, Craig Pulsipher, Raphael J. Landovitz

Erschienen in: Current HIV/AIDS Reports | Ausgabe 4/2019

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Abstract

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.

Recent Findings

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.

Summary

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.

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.CrossRefPubMedPubMedCentral

Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367(5):399–410. https://doi.org/10.1056/NEJMoa1108524.CrossRefPubMedPubMedCentral

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.

• 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.

AIDS Vaccine Advocacy Coalition (AVAC). Regulatory status of Truvada for PrEP. 2019.

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.CrossRefPubMedPubMedCentral

Siegler A, Mouhanna F, Mera Giler R, Weiss KM, Pembleton E, Guest JL, et al. The prevalence of PrEP use and the PrEP-to-need ratio in the fourth quarter of 2017, United States. Ann Epidemiol. 2018;28:841–9. https://doi.org/10.1016/j.annepidem.2018.06.005.CrossRefPubMedPubMedCentral

Anderson PL, Reirden D, Castillo-Mancilla J. Pharmacologic considerations for Preexposure prophylaxis in transgender women. J Acquir Immune Defic Syndr. 2016;72(Suppl 3):S230–4. https://doi.org/10.1097/QAI.0000000000001105.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.

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.

17.

Seifert SM, Glidden DV, Meditz AL, Castillo-Mancilla JR, Gardner EM, Predhomme JA, et al. Dose response for starting and stopping HIV preexposure prophylaxis for men who have sex with men. Clin Infect Dis. 2015;60(5):804–10. https://doi.org/10.1093/cid/ciu916.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.

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.CrossRefPubMedPubMedCentral

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.

27.

Denton PW, Garcia JV. Mucosal HIV-1 transmission and prevention strategies in BLT humanized mice. Trends Microbiol. 2012;20(6):268–74. https://doi.org/10.1016/j.tim.2012.03.007.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.

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.

33.

Radzio J, Spreen W, Yueh YL, Mitchell J, Jenkins L, Garcia-Lerma JG, et al. The long-acting integrase inhibitor GSK744 protects macaques from repeated intravaginal SHIV challenge. Sci Transl Med. 2015;7(270):270ra5. https://doi.org/10.1126/scitranslmed.3010297.CrossRefPubMed

34.

Andrews CD, Spreen WR, Mohri H, Moss L, Ford S, Gettie A, et al. Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus. Science. 2014;343(6175):1151-4. https://doi.org/10.1126/science.1248707.CrossRefPubMedPubMedCentral

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.

36.

Andrews CD, Bernard LS, Poon AY, Mohri H, Gettie N, Spreen WR, et al. Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251. AIDS. 2017;31(4):461–7. https://doi.org/10.1097/QAD.0000000000001343.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.

42.

Landovitz RJ, Kofron R, McCauley M. The promise and pitfalls of long-acting injectable agents for HIV prevention. Curr Opin HIV AIDS. 2016;11(1):122–8. https://doi.org/10.1097/coh.0000000000000219.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.

47.

Marrazzo JM, Ramjee G, Richardson BA, Gomez K, Mgodi N, Nair G, et al. Tenofovir-based Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015;372(6):509-18. https://doi.org/10.1056/NEJMoa1402269.CrossRefPubMedPubMedCentral

48.

Cranston RD, Lama JR, Richardson BA, Carballo-Diéguez A, Kunjara Na Ayudhya RP, Liu K, et al. MTN-017: a rectal phase 2 extended safety and acceptability study of Tenofovir reduced-glycerin 1% gel. Clin Infect Dis. 2017;64(5):614–20. https://doi.org/10.1093/cid/ciw832.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

50.

Nel A, Haazen W, Nuttall J, Romano J, Rosenberg Z, van Niekerk N. A safety and pharmacokinetic trial assessing delivery of dapivirine from a vaginal ring in healthy women. AIDS. 2014;28(10):1479–87. https://doi.org/10.1097/QAD.0000000000000280.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

53.

Romano J, Variano B, Coplan P, Van Roey J, Douville K, Rosenberg Z, et al. Safety and availability of dapivirine (TMC120) delivered from an intravaginal ring. AIDS Res Hum Retrovir. 2009;25(5):483–8. https://doi.org/10.1089/aid.2008.0184.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

55.

Baeten JM, Palanee-Phillips T, Brown ER, Schwartz K, Soto-Torres LE, Govender V, et al. Use of a vaginal ring containing Dapivirine for HIV-1 prevention in women. N Engl J Med. 2016;375(22):2121–32. https://doi.org/10.1056/NEJMoa1506110.CrossRefPubMedPubMedCentral

56.

Nel A, van Niekerk N, Kapiga S, Bekker LG, Gama C, Gill K, et al. Safety and efficacy of a Dapivirine vaginal ring for HIV prevention in women. N Engl J Med. 2016;375(22):2133–43. https://doi.org/10.1056/NEJMoa1602046.CrossRefPubMed

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.

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.

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMed

63.

Cunha-Reis C, Machado A, Barreiros L, Araujo F, Nunes R, Seabra V, et al. Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs. J Control Release. 2016;243:43–53. https://doi.org/10.1016/j.jconrel.2016.09.020.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

65.

Robinson JA, Marzinke MA, Bakshi RP, Fuchs EJ, Radebaugh CL, Aung W, et al. Comparison of Dapivirine vaginal gel and film formulation pharmacokinetics and pharmacodynamics (FAME 02B). AIDS Res Hum Retrovir. 2017;33(4):339–46. https://doi.org/10.1089/AID.2016.0040.CrossRefPubMedPubMedCentral

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.

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.CrossRefPubMedPubMedCentral

68.

Donnelly RF, Larraneta E. Microarray patches: potentially useful delivery systems for long-acting nanosuspensions. Drug Discov Today. 2018;23(5):1026–33. https://doi.org/10.1016/j.drudis.2017.10.013.CrossRefPubMed

69.

Arnou R, Eavis P, Pardo JR, Ambrozaitis A, Kazek MP, Weber F. Immunogenicity, large scale safety and lot consistency of an intradermal influenza vaccine in adults aged 18-60 years: randomized, controlled, phase III trial. Hum Vaccin. 2010;6(4):346–54.CrossRefPubMed

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.

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.

74.

Gautam R, Nishimura Y, Pegu A, Nason MC, Klein F, Gazumyan A, et al. A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges. Nature. 2016;533(7601):105–9. https://doi.org/10.1038/nature17677.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

77.

Pardi N, Secreto AJ, Shan X, Debonera F, Glover J, Yi Y, et al. Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge. Nat Commun. 2017;8:14630. https://doi.org/10.1038/ncomms14630.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

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.CrossRefPubMedPubMedCentral

82.

Grooms TN, Vuong HR, Tyo KM, Malik DA, Sims LB, Whittington CP, et al. Griffithsin-modified electrospun fibers as a delivery scaffold to prevent HIV infection. Antimicrob Agents Chemother. 2016;60(11):6518–31. https://doi.org/10.1128/AAC.00956-16.CrossRefPubMedPubMedCentral

83.

Ball C, Chou SF, Jiang Y, Woodrow KA. Coaxially electrospun fiber-based microbicides facilitate broadly tunable release of maraviroc. Mater Sci Eng C Mater Biol Appl. 2016;63:117–24. https://doi.org/10.1016/j.msec.2016.02.018.CrossRefPubMedPubMedCentral

84.

Ball C, Woodrow KA. Electrospun solid dispersions of Maraviroc for rapid intravaginal preexposure prophylaxis of HIV. Antimicrob Agents Chemother. 2014;58(8):4855–65. https://doi.org/10.1128/AAC.02564-14.CrossRefPubMedPubMedCentral

85.

Krogstad EA, Woodrow KA. Manufacturing scale-up of electrospun poly(vinyl alcohol) fibers containing tenofovir for vaginal drug delivery. Int J Pharm. 2014;475(1–2):282–91. https://doi.org/10.1016/j.ijpharm.2014.08.039.CrossRefPubMedPubMedCentral

86.

Carson D, Jiang Y, Woodrow KA. Tunable release of multiclass anti-HIV drugs that are water-soluble and loaded at high drug content in polyester blended electrospun fibers. Pharm Res. 2016;33(1):125–36. https://doi.org/10.1007/s11095-015-1769-0.CrossRefPubMed

87.

Hoang T, Date AA, Ortiz Ortiz J, Young TW, Bensouda S, Xiao P, et al. Development of rectal enema as microbicide (DREAM): preclinical progressive selection of a tenofovir prodrug enema. Eur J Pharm Biopharm. 2018;138:23–9. https://doi.org/10.1016/j.ejpb.2018.05.030.CrossRefPubMedPubMedCentral

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.

89.

Khan AB, Thakur RS. Design and evaluation of mucoadhesive vaginal tablets of tenofovir disoproxil fumarate for pre-exposure prophylaxis of HIV. Drug Dev Ind Pharm. 2018;44(3):472–83. https://doi.org/10.1080/03639045.2017.1399272.CrossRefPubMed

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.CrossRefPubMedPubMedCentral

Titel: Current and Future PrEP Medications and Modalities: On-demand, Injectables, and Topicals
verfasst von: Matthew R. Beymer
Ian W. Holloway
Craig Pulsipher
Raphael J. Landovitz
Publikationsdatum: 20.06.2019
Verlag: Springer US
Erschienen in: Current HIV/AIDS Reports / Ausgabe 4/2019
Print ISSN: 1548-3568
Elektronische ISSN: 1548-3576
DOI: https://doi.org/10.1007/s11904-019-00450-9

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Current and Future PrEP Medications and Modalities: On-demand, Injectables, and Topicals

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Purpose of Review

Recent Findings

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Abstract

Purpose of Review

Recent Findings

Summary

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