171 HIV (highly active antiretroviral therapy, HAART) 1997 90-90-90 (pre-exposure prophylaxis, PrEP) PrEP 40~90% PrEP tenofovir PrEP PrEP PrEP 2018:28:171-182 107 5 1 107 7 6 360 31 (02) 8966-7000 2182 DOI: 10.6526/ICJ.201808_28(4).0003 107 8
172 HIV 90-90-90 1981 (acquired immune deficiency syndrome, AIDS) (highly active antiretroviral therapy, HAART) (human immunodeficiency virus, HIV) (genetic barrier) 1~2 HIV HIV HIV HIV [1] (United Nations Programme on HIV/AIDS, UNAIDS) 2014 90-90-90 90-90-90 2020 90% 90% 90% 72% HIV 2030 95-95-95 HIV 86% HIV 90-90-90 90% 90% 90% [1] HIV HIV 2017 79%-87%-
173 90% HIV (pre-exposure prophylaxis, PrEP) HIV HIV tenofovir disoproxil/emtricitabine (TDF/FTC) PrEP HIV truvada PrEP PrEP 100% PrEP [2] HIV Cremin 2013 HIV HAART [3] HIV ( ) () HIV 1.38% 0.51% () (PrEP) 0.04% 13 (World Health Organization, WHO) 2015 PrEP HIV 3% [4] (The European AIDS Clinical Society, EACS) 2017 TDF/FTC PrEP [5] 107 8
174 HIV HAART TDF/FTC TDF/FTC tenofovir ( TDF ) 7 21 [6] TDF/FTC ( HIV ) ( ) (transgender women) Grant 2010 iprex ( ) TDF/FTC 44% (95% 15~63%, P = 0.005) PrEP 9% [7] iprex-ole 2 TDF/FTC 44% (95% - 31~77%) 2~3 84% (95% 21~99%) 4 95% (95% 88~100%) [8] PrEP 2016 PROUD (Post-exposure Prophylaxis, PEP) PrEP 86% (95% 64~96%) [9] Molina IPERGAY PrEP (on-demand PrEP) 2~24 2 TDF/FTC
175 PrEP (% HR) [95% ] () [2,4,5] iprex [7] TDF+FTC 2,499 44% [95% CI, 15~63] PROUD [9] TDF+FTC 544 86% [95% CI, 64~96] early vs delay IPERGAY [10] TDF+FTC 414 86% [95% CI, 40~98] (On-demand) () [2,4,5] Partners PrEP [11] TDF 4,747 67% [95% CI, 44~81] TDF+FTC 75% [95% CI, 55~87] () [2,4,5] TDF2 [13] TDF+FTC 1,219 62% [95% CI, 22~83] FEM-PrEP [14] TDF+FTC 2,120 HR 0.94 [95% CI, 0.59~1.52] VOICE [15] TDF 12,320 HR 1.49 [95% CI, 0.97~2.29] TDF+FTC HR 1.04 [95% CI, 0.73~1.49] TFV gel HR 0.85 [95% CI, 0.61~1.21] MVC-PrEP [22] MVC MVC+TDF 188 MVC+FTC TDF+FTC () [2,4,5] Bangkok TDF [16] TDF 2,413 48.9% [95% CI, 9.6~72.2] TDF/FTC 1 TDF/ FTC 7 TDF/FTC 86% (95% 40~98%) (14% vs. 5%, P = 0.002)[10] 107 8
176 HIV PrEP 2 B TDF B 15 PrEP 4,747 Partners-PrEP TDF/FTC HIV 75% (95% 55~87%) 84% 66% TDF HIV 67% (95% 44~81%) 63% 71% B B B [11] ( 6.2 6.8 ) [12] 1,219 TDF/FTC 62.2% (95% 21.5~83.4%) PrEP (P < 0.001) [13] FEM-PrEP VOICE TDF TDF/FTC 4~-49% ( )
177 50% [14,15] iprex 2,413 Bangko TDF TDF 80% (daily directly observed treatment, DOT) TDF 48.9% HIV (95% 9.6~72.2%) 40 TDF TDF TDF 73.5% (95% 16.6~94%) [16] ( ) PrEP 9,230 HIV ( FTC ) 5 0.05% 6,678 1 0.015% PrEP 60% Abbas (1) (antiretroviral therapy, ART) (2) PrEP (3) ART PrEP ART PrEP 20% 21% PrEP PrEP iprex [7] 0 1,251 0 1,248 Partners PrEP [11] 0 3,163 0 1,584 TDF2 [13] 0 610 0 606 FEM-PrEP [14] 4 1,024 1 1,032 VOICE [15] 1 1,978 0 999 Bangkok TDF [16] 0 1,204 0 1,209 5 9,230 1 6,678 107 8
178 HIV 6.6% 0.5% ART PrEP 35% 8.2% ART PrEP ART PrEP [17] ART PrEP ART PrEP TDF/FTC ART TDF/ FTC 37% 7.2% ART TDF/FTC PrEP 80% 90% 80% 12% PrEP HIV PrEP PrEP PrEP HIV [17] PrEP PrEP 2017 (conference on retroviruses and opportunistic infections, CROI) 55 TDF/FTC 100 90 TDF 2,243 2,258 fmol/punch (> 1,250 fmol/ punch ) HIV ART (wild type) TDF PrEP
179 PrEP HIV [18] Partners-PrEP PrEP HIV (sexually transmitted infections, STI) B C Sharon LH TDF [19] PrEP PrEP PrEP TDF/FTC tenofovir disoproxil (creatinine clearance rate, CrCl) 50 ml/min tenofovir alafenamide (TAF) TDF TAF (CrCl > 30 ml/ min) [20] TAF/FTC PrEP PrEP PrEP TDF rilpivirine TDF CCR5 maraviroc (MVC) 188 MVC MVC/TDF MVC/FTC TDF/FTC 48 2% 30% 60% [21] PrEP 107 8
180 HIV 40~90% PrEP tenofovir PrEP PrEP PrEP 1. UNAIDS (2017, January 1): 90-90-90-An ambitious treatment target to help end the AIDS epidemic. Available http://www.unaids.org/sites/ default/files/media_asset/90-90-90_en.pdf 2. (2016 5 2 ) http://www. aids-care.org.tw/ 3. Cremin I, Alsallaq R, Dybul M, et al: The new role of antiretrovirals in combination HIV prevention: a mathematical modelling analysis. AIDS 2013;27:447-58. 4. WHO (2015, September 30): Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. Available http://www.who. int/hiv/pub/guidelines/earlyrelease-arv/en/ 5. European AIDS Clinical Society (2017, October): The 2017 European AIDS Clinical Society (EACS) Guidelines for the treatment of adult HIV-positive persons version 9.0. Available http://www. eacsociety.org/files/guidelines_9.0-english 6. Cottrell ML, Srinivas N, Kashuba ADM: Pharmacokinetics of Antiretrovirals in Mucosal Tissue. Expert Opin Drug Metab Toxicol 2015;11:893-905. 7. Grant RM, Lama JR, Anderson PL, et al: Preexposure chemoprophylaxis for HIV prevention in men who have sex with men (iprex). N Engl J Med 2010;363:2587-99. 8. Grant RM, Anderson PL, McMahan V, et al: Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men (iprex-ole): a cohort study. Lancet Infect Dis 2014;14:820-9. 9. McCormack S, Dunn DT, Desai M, et al: Preexposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet 2016;387:53-60. 10. Molina JM, Capitant C, Spire B, et al: On-demand preexposure prophylaxis in men at high risk for HIV-1 infection (IPERGAY). N Engl J Med 2015;373:2237-46. 11. Baeten JM, Donnell D, Ndase P, et al: Antiretroviral prophylaxis for HIV prevention in heterosexual men and women (Partners PrEP). N Engl J Med 2012;367:399-410. 12. Mugwanya KK, Donnell D, Celum C, et al: Sexual behaviour of heterosexual men and women receiving antiretroviral pre-exposure prophylaxis for HIV prevention: a longitudinal analysis. Lancet Infect Dis 2013;13:1021-8. 13. Thigpen MC, Kebaabetswe PM, Paxton LA, et al: Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.N Engl J Med 2012;367:423-34. 14. Van Damme L, Corneli A, Ahmed K, et al: Preexposure prophylaxis for HIV infection among African women (FEM-PrEP). N Engl J Med 2012;367:411-22. 15. Marrazzo JM, Ramjee G, Richardson BA, et al: Tenofovir-based preexposure prophylaxis for HIV
181 infection among African women (VOICE). N Engl J Med 2015;372:509-18. 16. Choopanya K, Martin M, Suntharasamai P, et al: Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, doubleblind, placebo-controlled phase 3 trial. Lancet 2013;381:2083-90. 17. Abbas UL, Glaubius R, Mubayi A, et al: Antiretroviral therapy and pre-exposure prophylaxis: combined impact on HIV transmission and drug resistance in South Africa. J Infect Dis 2013;208:224-34. 18. Elske H, Godelieve JB (2017, February 13): Acute infection with a wild-type HIV-1 virus in PrEP user with high TDF level. Conference on Retroviruses and Opportunistic Infections (CROI) Abstract Number: 953. Available http://www. croiconference.org/sessions/acute-infection-wildtype-hiv-1-virus-prep-user-high-tdf-levels. 19. Sharon LH, Leslie AM, Katherine B, et al: (2017, February 13): Impact of vaginal microbiota on genital tissue and plasma concentration of tenofovir. Conference on Retroviruses and Opportunistic Infections (CROI) Abstract Number: 86LB. Available http://www.croiwebcasts.org/ p/2017croi/croi33459. 20. Micromedex: Drug information of tenofovir alafenamide/emtricitabine. Available http:// www.micromedexsolutions.com/micromedex2/ librarian/pfdefaultactionid/evidencexpert. DoIntegratedSearch#. 21. Gulick RM, Wilkin TJ, Chen YQ, et al: Safety and tolerability of maraviroc-containing regimens to prevent HIV infection in women: a phase 2 randomized trial. Ann Intern Med 2017;167:384-93. 107 8
182 HIV The Impact of Pre-exposure Prophylaxis on HIV Infection Control Ming-Shen Lin, Wei-Lun Chang, Shu-Hui Sun Department of Pharmacy, Far Eastern Memorial Hospital, New Taipei, Taiwan The mortality associated with human immunodeficiency virus infection has declined with current treatment and public health policy. For better disease control, UNAIDS established a new strategy on HIV management and a new, ambitious treatment target. Achieving these targets by 2020 will potentially end the AIDS epidemic by 2030, which in turn will generate profound health and economic benefits. Although many strategies had been implemented to achieve these targets, further interventions are required. Pre-exposure Prophylaxis (PrEP) is key to promote current strategies. Current clinical trials indicate that PrEP offers great protection from HIV infection depending on various populations. But sadly, no strategy is perfect. PrEP with poor adherence provides not only poor protection but also potentially increase resistant mutations. For this reason, we need further education and support policy to enhance patient s adherence. PrEP is definitely a landmark for HIV infection control. It requires more support from different sectors to make it better. It also needs more empathy and tolerance given from others. I believe that we can bring us closer to the goal of zero HIV infection in the future. Key words: Human immunodeficiency virus (HIV), highly active antiretroviral therapy, HAART, Pre-exposure Prophylaxis (PrEP), tenofovir disoproxil/emtricitabine (TDF/FTC), acquired immune deficiency syndrome (AIDS)