[1. M. Peeters, M. D’Arc and E. Delaporte, The origin and diversity of human retroviruses, AIDS Rev. 16 (2014) 23–34.]Search in Google Scholar
[2. World Health Organization, Progress Report 2016: Prevent HIV, Test and Treat All: WHO Support for Country Impact, WHO, 2016; http://www.who.int/iris/handle/10665/251713; last access date January 18, 2019.]Search in Google Scholar
[3. J. M. Excler and N. L. Michael, Lessons from HIV-1 vaccine efficacy trials, Curr. Opin. HIV AIDS11 (2016) 607–613; https://doi.org/10.1097/COH.000000000000031210.1097/COH.0000000000000312]Search in Google Scholar
[4. Z. A. Stein, Vaginal microbicides and prevention of HIV infection, Lancet343 (1994) 362–363; https://doi.org/10.1016/S0140-6736(94)91205-X10.1016/S0140-6736(94)91205-X]Search in Google Scholar
[5. J. Balzarini and L. Van Damme, Microbicide drug candidates to prevent HIV infection, Lancet369 (2007) 787–797; https://doi.org/10.1016/S0140-6736(07)60202-510.1016/S0140-6736(07)60202-5]Search in Google Scholar
[6. L. M. Ferguson and L. C. Rohan, The importance of the vaginal delivery route for antiretrovirals in HIV prevention, Ther. Deliv.2 (2011) 1535–1550; https://doi.org/10.4155/tde.11.12610.4155/tde.11.126331433722468220]Search in Google Scholar
[7. Z. Si, N. Madani, J. M. Cox, J. J. Chruma, J. C. Klein, A. Schön, N. Phan, L. Wang, A. C. Biorn, S. Cocklin, I. Chaiken, E. Freire, A. B. Smith III and J. G. Sodroski, Small-molecule inhibitors of HIV-1 entry block receptor-induced conformational changes in the viral envelope glycoproteins, Proc. Natl. Acad. Sci. USA101 (2004) 5036–5041; https://doi.org/10.1073/pnas.030795310110.1073/pnas.030795310138736915051887]Search in Google Scholar
[8. L. D. Saravolatz and M. S. Saag, Emtricitabine, a new antiretroviral agent with activity against HIV and hepatitis B virus, Clin. Infect. Dis.42 (2006) 126–131; https://doi.org/http://doi.org/10.1086/49834810.1086/49834816323102]Search in Google Scholar
[9. N. Ray, Maraviroc in the treatment of HIV infection, Drug Des. Devel. Ther.2 (2008) 151–161; https://doi.org/10.2147/DDDT.S347410.2147/DDDT.S3474276119219920903]Search in Google Scholar
[10. J. Kenney, M. Aravantinou, R. Singer, M. Hsu, A. Rodriguez, L. Kizima, C. J. Abraham, R. Menon, S. Seidor, A. Chudolij, A. Gettie, J. Blanchard, J. D. Lifson, M. Piatak Jr., J. A. Fernández-Romero, T. M. Zydowsky and M. Robbiani, Antiretroviral/zinc combination gel provides 24 hours of complete protection against vaginal SHIV infection in macaques, PLoS ONE6 (2011) e15835; https://doi.org/10.1371/journal.pone.001583510.1371/journal.pone.0015835301641321246052]Search in Google Scholar
[11. T. Bar-Magen, R. D. Sloan, D. A. Donahue, B. D. Kuhl, A. Zabeida, H. Xu, M. Oliveira, D. J. Hazuda and M. A. Wainberg, Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor, J. Virol.84 (2010) 9210–9216; https://doi.org/10.1128/JVI.01164-1010.1128/JVI.01164-10293759720610719]Search in Google Scholar
[12. A. S. Ray, M. W. Fordyce and M. J. Hitchcock, Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of human immunodeficiency virus, Antiviral Res.125 (2016) 63–70; https://doi.org/10.1016/j.antiviral.2015.11.00910.1016/j.antiviral.2015.11.00926640223]Search in Google Scholar
[13. B. P. Kearney, J. F. Flaherty and J. Shah, Tenofovir disoproxil fumarate clinical pharmacology and pharmacokinetics, Clin. Pharmacokinet.43 (2004) 595–616; https://doi.org/10.2165/00003088-200443090-0000310.2165/00003088-200443090-00003]Search in Google Scholar
[14. S. Di Fabio, J. Van Roey, G. Giannini, G. van den Mooter, M. Spada, A. Binelli, M. F. Pirillo, E. Germinario, F. Belardelli, M. P. de Bethune and S. Vella, Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by the non-nucleoside reverse transcriptase inhibitor TMC120 in a gel formulation, AIDS17 (2003) 1597–1604; https://doi.org/10.1097/01.aids.0000072663.21517.6310.1097/00002030-200307250-00003]Search in Google Scholar
[15. J. Balzarini, H. Pelemans, S. Aquaro, C. F. Perno, M. Witvrouw, D. Schols, E. De Clercq and A. Karlsson, Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication, Mol. Pharmacol. 50 (1996) 394–401.]Search in Google Scholar
[16. T. J. Wilkin, Z. Su, A. Krambrink, J. Long, W. Greaves, R. Gross, M. D. Hughes, C. Flexner, P. R. Skolnik, E. Coakley, C. Godfrey, M. Hirsch, D. R. Kuritzkes and R. M. Gulick, Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1-infected, treatment-experienced patients, J. Acquir. Immune Defic. Syndr.5 (2010) 470–476; http://doi.org/10.1097/QAI.0b013e3181e2cba010.1097/QAI.0b013e3181e2cba0]Search in Google Scholar
[17. N. J. Alexander, E. Baker, M. Kaptein, U. Karc, L. Mille and E. Zampaglione, Why consider vaginal drug administration?, Fertil. Steril.82 (2004) 1–12; https://doi.org/10.1016/j.fertnstert.2004.01.02510.1016/j.fertnstert.2004.01.025]Search in Google Scholar
[18. D. R. Friend and P. F. Kiser, Assessment of topical microbicides to prevent HIV-1 transmission: Concepts, testing, lessons learned, Antiviral Res.99 (2013) 391–400; https://doi.org/10.1016/j.antiviral.2013.06.02110.1016/j.antiviral.2013.06.021]Search in Google Scholar
[19. D. J. Schaeffer and V. S. Krylov, Anti-HIV activity of extracts and compounds from algae and cyanobacteria, Ecotoxicol. Environ. Saf.45 (2000) 208–227; https://doi.org/10.1006/eesa.1999.186210.1006/eesa.1999.1862]Search in Google Scholar
[20. B. Cutler and J. Justman, Vaginal microbicides and the prevention of HIV transmission, Lancet Infect. Dis.8 (2008) 685–697; https://doi.org/10.1016/S1473-3099(08)70254-810.1016/S1473-3099(08)70254-8]Search in Google Scholar
[21. D. Huskens, K. Vermeire, A. T. Profy and D. Schols, The candidate sulfonated microbicide, PRO 2000, has potential multiple mechanisms of action against HIV-1, Antiviral Res.84 (2009) 38–47; https://doi.org/10.1016/j.antiviral.2009.07.01310.1016/j.antiviral.2009.07.01319664662]Search in Google Scholar
[22. L. Van Damme, R. Govinden, F. M. Mirembe, F. Guédou, S. Solomon, M. L. Becker, B. S. Pradeep, A. K. Krishnan, M. Alary, B. Pande, G. Ramjee, J. Deese, T. Crucitti, D. Taylor and CS study group, Lack of effectiveness of cellulose sulfate gel for the prevention of vaginal HIV transmission, N. Engl. J. Med.359 (2008) 463–472; https://doi.org/10.1056/NEJMoa070795710.1056/NEJMoa070795718669425]Search in Google Scholar
[23. D. Tyssen, S. A. Henderson, A. Johnson, J. Sterjovski, K. Moore, J. La, M. Zanin, S. Sonza, P. Karellas, M. P. Giannis, G. Krippner, S. Wesselingh, T. McCarthy, P. R. Gorry, P. A. Ramsland, R. Cone, J. R. Paull, G. R. Lewis and G. Tachedjian, Structure activity relationship of dendrimer microbicides with dual action antiviral activity, PLoS ONE5 (2010) e12309; https://doi.org/10.1371/journal.pone.001230910.1371/journal.pone.0012309292589320808791]Search in Google Scholar
[24. D. Serfaty, Contraception during perimenopause: The spermicides option, J. Gynecol. Obstet. Hum. Reprod. 46 (2017) 211–218; https://doi.org/10.1016/j.jogoh.2016.10.00710.1016/j.jogoh.2016.10.00728403917]Search in Google Scholar
[25. L. Van Damme, G. Ramjee, M. Alary, B. Vuylsteke, V. Chandeying, H. Rees, P. Sirivongrangson, L. Mukenge-Tshibaka, V. Ettiègne-Traoré, C. Uaheowitchai, S. S. Karim, B. Mâsse, J. Perriëns, M. Laga and COL-1492 study group, Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial, Lancet360 (2002) 971–977; https://doi.org/10.1016/S0140-6736(02)11079-810.1016/S0140-6736(02)11079-8]Search in Google Scholar
[26. J. Kreiss, E. Ngugi, K. Holmes, J. Ndinya-Achola, P. Waiyaki, P. L. Roberts, I. Ruminjo, R. Sajabi, J. Kimata, T. R. Fleming, A. Anzala, D. Holton and F. Plummer, Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes, JAMA268 (1992) 477–482; https://doi.org/10.1001/jama.1992.0349004005302510.1001/jama.1992.03490040053025]Search in Google Scholar
[27. R. E. Roddy, L. Zekeng, K. A. Ryan, U. Tamoufé, S. S. Weir and E. L. Wong, A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases, N. Engl. J. Med.339 (1998) 504–510; https://doi.org/10.1056/NEJM19980820339080310.1056/NEJM199808203390803]Search in Google Scholar
[28. D. Wilkinson, M. Tholandi, G. Ramjee and G. W. Rutherford, Nonoxynol-9 spermicide for prevention of vaginally acquired HIV and other sexually transmitted infections: systematic review and meta-analysis of randomised controlled trials including more than 5000 women, Lancet Infect. Dis. 2 (2002) 613–617; https://doi.org/10.1016/S1473-3099(02)00396-110.1016/S1473-3099(02)00396-1]Search in Google Scholar
[29. P. J. Feldblum, A. Adeiga, R. Bakare, S. Wevill, A. Lendvay, F. Obadaki, M. O. Olayemi, L. Wang, K. Nanda and W. Rountree, SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria, PLoS ONE3 (2008) e1474; https://doi.org/10.1371/journal.pone.000147410.1371/journal.pone.0001474]Search in Google Scholar
[30. S. Skoler-Karpoff, G. Ramjee, K. Ahmed, L. Altini, M. G. Plagianos, B. Friedland, S. Govender, A. De Kock, N. Cassim, T. Palanee, G. Dozier, R. Maguire and P. Lahteenmaki, Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial, Lancet372 (2008) 1977–1987; https://doi.org/10.1016/S0140-6736(08)61842-510.1016/S0140-6736(08)61842-5]Search in Google Scholar
[31. The Carraguard Phase II South Africa study team, Expanded safety and acceptability of the candidate vaginal microbicide Carraguard® in South Africa, Contraception82 (2010) 563–571; https://doi.org/10.1016/j.contraception.2010.04.01910.1016/j.contraception.2010.04.019]Search in Google Scholar
[32. S. McCormack, G. Ramjee, A. Kamali, H. Rees, A. M. Crook, M. Gafos, U. Jentsch, R. Pool, M. Chisembele, S. Kapiga, R. Mutemwa, A. Vallely, T. Palanee, Y. Sookrajh, C. J. Lacey, J. Darbyshire, H. Grosskurth, A. Profy, A. Nunn, R. Hayes and J. Weber, PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides development programme 301): a phase 3, randomised, double-blind, parallel-group trial, Lancet376 (2010) 1329–1337; https://doi.org/10.1016/S0140-6736(10)61086-010.1016/S0140-6736(10)61086-0]Search in Google Scholar
[33. V. Pirrone, B. Wigdahl and F. C. Krebs, The rise and fall of polyanionic inhibitors of the human immunodeficiency virus type 1, Antiviral. Res.90 (2011) 168–182; https://doi.org/10.1016/j.antiviral.2011.03.17610.1016/j.antiviral.2011.03.17621439325]Search in Google Scholar
[34. T. D. McCarthy, P. Karellas, S. A. Henderson, M. Giannis, D. F. O’Keefe, G. Heery, J. R. Paull, B. R. Matthews and G. Holan, Dendrimers as drugs: discovery and preclinical and clinical development of dendrimer-based microbicides for HIV and STI prevention, Mol. Pharm. 2 (2005) 312–318; https://doi.org/10.1021/mp050023q10.1021/mp050023q16053334]Search in Google Scholar
[35. C. F. Price, D. Tyssen, S. Sonza, A. Davie, S. Evans, G. R. Lewis, S. Xia, T. Spelman, P. Hodsman, T. R. Moench, A. Humberstone, J. R. Paull and G. Tachedjian, SPL7013 Gel (VivaGel®) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans, PLoS ONE6 (2011) e24095; https://doi.org/10.1371/journal.pone.002409510.1371/journal.pone.0024095]Search in Google Scholar
[36. M. Hiorth, S.Nilsen and I. Tho, Bioadhesive mini-tablets for vaginal drug delivery, Pharmaceutics6 (2014) 494–511; https://doi.org/10.3390/pharmaceutics603049410.3390/pharmaceutics6030494]Search in Google Scholar
[37. C. Kempf, P. Jentsch, F. B. Barre-Sinoussi, B. Poirier, J. J. Morgenthaler, A. Morell and D. Germann, Inactivation of human immunodeficiency virus (HIV) by low pH and pepsin, J. Acquir. Immune Defic. Syndr. 4 (1991) 828–830.]Search in Google Scholar
[38. S. S. A. Karim, B. A. Richardson, G. Ramjee, I. F. Hoffman, Z. M. Chirenje, T. Taha, M. Kapina, L. Maslankowski, A. Coletti, A. Profy, T. R. Moench, E. Piwowar-Manning, B. Mâsse, S. L. Hillier, L. Soto-Torres and HIV prevention trials network (HPTN) 035 study team, Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women, AIDS25 (2011) 957–966; https://doi.org/10.1097/QAD.0b013e32834541d910.1097/QAD.0b013e32834541d9]Search in Google Scholar
[39. K. H. Mayer, L. A. Maslankowski, F. Gai, W. M. El-Sadr, J. Justman, A. Kwiecien, B. Mâsse, S. H. Eshleman, C. Hendrix, K. Morrow, J. F. Rooney, L. Soto-Torres and HPTN 050 protocol team, Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women, AIDS20 (2006) 543–451; https://doi.org/10.1097/01.aids.0000210608.70762.c310.1097/01.aids.0000210608.70762.c3]Search in Google Scholar
[40. Q. A. Karim, S. S. A. Karim, J. A. Frohlich, A. C. Grobler, C. Baxter, L. E. Mansoor, A. B. Kharsany, S. Sibeko, K. P. Mlisana, Z. Omar, T. N. Gengiah, S. Maarschalk, N. Arulappan, M. Mlotshwa, L. Morris, D. Taylor and CAPRISA 004 trial group, Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women, Science329 (2010) 1168–1174; https://doi.org/10.1126/science.119374810.1126/science.1193748]Search in Google Scholar
[41. A. D. Kashuba, T. N. Gengiah, L. Werner, K. H. Yang, N. R. White, Q. A. Karim and S. S. A. Karim, Genital tenofovir concentrations correlate with protection against HIV infection in the CAPRISA 004 trial: Importance of adherence for microbicide effectiveness, J. Acquir. Immune Defic. Syndr. 69 (2015) 264–269; https://doi.org/10.1097/QAI.000000000000060710.1097/QAI.0000000000000607]Search in Google Scholar
[42. J. M. Marrazzo, G. Ramjee, B. A. Richardson, K. Gomez, N. Mgodi, G. Nair, T. Palanee, C. Nakabiito, A. van der Straten, L. Noguchi, C. W. Hendrix, J. Y. Dai, S. Ganesh, B. Mkhize, M. Taljaard, U. M. Parikh, J. Piper, B. Mâsse, C. Grossman, J. Rooney, J. L. Schwartz, H. Watts, M. A. Marzinke, S. L. Hillier, I. M. McGowan, Z. M. Chirenje and VOICE study team, Tenofovir-based preexposure prophylaxis for HIV infection among African women, N. Engl. J. Med. 372 (2015) 509–518; https://doi.org/10.1056/NEJMoa140226910.1056/NEJMoa1402269]Search in Google Scholar
[43. Q. A. Karim, C. Baxter and S. A. Karim, Microbicides and their potential as a catalyst for multi-purpose sexual and reproductive health technologies, BJOG12 (2014) 53–61; https://doi.org/10.1111/1471-0528.1284310.1111/1471-0528.12843]Search in Google Scholar
[44. H. Rees, S. A. Delany-Moretlwe, C. Lombard, D. Baron, R. Panchia, L. Myer, J. L. Schwartz, G. F. Doncel and G. Gray, FACTS 001 phase III trial of pericoital tenofovir 1% gel for HIV prevention in women, in Conference on Retroviruses and Opportunistic Infections, February 23-26, 2015, Seattle, Washington, abstract no. 26LB; https://www.croiconference.org/sessions/facts-001-phase-iii-trial-pericoital-tenofovir-1-gel-hiv-prevention-women; last access date January 18, 2019.10.1016/S1473-3099(18)30428-6]Search in Google Scholar
[45. L. E. Mansoor, Q. A. Karim, K. T. Mngadi, S. Dlamini, C. Montague, N. Nkomonde, N. Mvandaba, C. Baxter, T. N. Gengiah, N. Samsunder, H. Dawood, A. Grobler, J. A. Frohlich and S. S. A. Karim, Assessing the implementation effectiveness and safety of 1% tenofovir gel provision through family planning services in KwaZulu-Natal, South Africa: study protocol for an open-label randomized controlled trial, Trials15 (2014) Article ID 496 (9 pages); https://doi.org/10.1186/1745-6215-15-49610.1186/1745-6215-15-496430082825527071]Search in Google Scholar
[46. K. M. MacQueen, S. Dlamini, B. Perry, E. Okumu, S. Sortijas, C. Singh, D. Pillay, A. Majors, S. Jerome, S. Watson, S. A. Karim, Q. A. Karim and L. E. Mansoor, Social context of adherence in an open-label 1% tenofovir gel trial: gender dynamics and disclosure in KwaZulu-Natal, South Africa, AIDS Behav. 20 (2016) 2682–2691; https://doi.org/10.1007/s10461-016-1339-410.1007/s10461-016-1339-4506932726945585]Search in Google Scholar
[47. J. Cohen, Infectious disease. Vaginal microbiome affects HIV risk, Science353 (2016) 331; https://doi.org/10.1126/science.353.6297.33110.1126/science.353.6297.33127463647]Search in Google Scholar
[48. N. R. Klatt, R. Cheu, K. Birse, A. S. Zevin, M. Perner, L. Noël-Romas, A. Grobler, G. Westmacott, I. Y. Xie, J. Butler, L. Mansoor, L. R. McKinnon, J. S. Passmore, Q. A. Karim, S. S. A. Karim and A. D. Burgener, Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women, Science356 (2017) 938–945; https://doi.org/10.1126/science.aai938310.1126/science.aai938328572388]Search in Google Scholar
[49. A. M. Nel, P. Coplan, J. H. van de Wijgert, S. H. Kapiga, C. von Mollendorf, E. Geubbels, J. Vyankandondera, H. V. Rees, G. Masenga, I. Kiwelu, J. Moyes and S. C. Smythe, Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women, AIDS23 (2009) 1531–1538; https://doi.org/10.1097/QAD.0b013e32832c413d10.1097/QAD.0b013e32832c413d19550287]Search in Google Scholar
[50. A. M. Nel, S. C. Smythe, S. Habibi, P. E. Kaptur and J. W. Romano, Pharmacokinetics of 2 dapivirine vaginal microbicide gels and their safety vs. hydroxyethyl cellulose-based universal placebo gel, J. Acquir. Immune Defic. Syndr.55 (2010) 161–169; https://doi.org/10.1097/QAI.0b013e3181e3293a10.1097/QAI.0b013e3181e3293a20574411]Search in Google Scholar
[51. B. Devlin, J. Nuttall, S. Wilder, C. Woodsong and Z. Rosenberg, Development of dapivirine vaginal ring for HIV prevention, Antiviral Res.100 (2013) S3–S8; https://doi.org/10.1016/j.antiviral.2013.09.02510.1016/j.antiviral.2013.09.02524188702]Search in Google Scholar
[52. R. K. Malcolm, P. J. Boyd, C. F. McCoy and D. J. Murphy, Microbicide vaginal rings: Technological challenges and clinical development, Adv Drug Deliv Rev.103 (2016) 33–56; https://doi.org/10.1016/j.addr.2016.01.01510.1016/j.addr.2016.01.01526829289]Search in Google Scholar
[53. A. Nel, L. G. Bekker, E. Bukusi, E. Hellstrӧm, P. Kotze, C. Louw, F. Martinson, G. Masenga, E. Montgomery, N. Ndaba, A. van der Straten, N. van Niekerk and C. Woodsong, Safety, acceptability and adherence of dapivirine vaginal ring in a microbicide clinical trial conducted in multiple countries in Sub-Saharan Africa, PLoS ONE11 (2016) e0147743; https://doi.org/10.1371/journal.pone.014774310.1371/journal.pone.0147743478633626963505]Search in Google Scholar
[54. J. M. Baeten, T. Palanee-Phillips, E. R. Brown, K. Schwartz, L. E. Soto-Torres, V. Govender, N. M. Mgodi, F. Matovu Kiweewa, G. Nair, F. Mhlanga, S. Siva, L. G. Bekker, N. Jeenarain, Z. Gaffoor, F. Martinson, B. Makanani, A. Pather, L. Naidoo, M. Husnik, B. A. Richardson, U. M. Parikh, J. W. Mellors, M. A. Marzinke, C. W. Hendrix, A. van der Straten, G. Ramjee, Z. M. Chirenje, C. Nakabiito, T. E. Taha, J. Jones, A. Mayo, R. Scheckter, J. Berthiaume, E. Livant, C. Jacobson, P. Ndase, R. White, K. Patterson, D. Germuga, B. Galaska, K. Bunge, D. Singh, D. W. Szydlo, E. T. Montgomery, B. S. Mensch, K. Torjesen, C. I. Grossman, N. Chakhtoura, A. Nel, Z. Rosenberg, I. McGowan, S. Hillier, and MTN-020–ASPIRE study team, Use of a vaginal ring containing dapivirine for HIV-1 prevention in women, N. Engl. J. Med.375 (2016) 2121–2132; https://doi.org/10.1056/NEJMoa150611010.1056/NEJMoa1506110499369326900902]Search in Google Scholar
[55. A. Nel, N. van Niekerk, S. Kapiga, L. G. Bekker, C. Gama, K. Gill, A. Kamali, P. Kotze, C. Louw, Z. Mabude, N. Miti, S. Kusemererwa, H. Tempelman, H. Carstens, B. Devlin, M. Isaacs, M. Malherbe, W. Mans, J. Nuttall, M. Russell, S. Ntshele, M. Smit, L. Solai, P. Spence, J. Steytler, K. Windle, M. Borremans, S. Resseler, J. Van Roey, W. Parys, T. Vangeneugden, B. Van Baelen, Z. Rosenberg and Ring study team, Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women, N. Engl. J. Med. 375 (2016) 2133–2143; https://doi.org/10.1056/NEJMoa160204610.1056/NEJMoa160204627959766]Search in Google Scholar
[56. A. Nel, W. Haazen, M. Russell, J. Nuttall, N. Van Niekerk and N. Treijtel, Drug-drug interactions between the dapivirine vaginal ring (Ring-004) and miconazole nitrate vaginal capsule (Gyno-Daktarin®), AIDS Res. Hum. Retroviruses30 (2014) A144. https://doi.org/10.1089/aid.2014.5291.abstract10.1089/aid.2014.5291.abstract]Search in Google Scholar
[57. To assess the drug-drug interaction potential between dapivirine vaginal ring-004, containing 25 mg of dapivirine, and clotrimazole 10 mg/g (1%); https://clinicaltrials.gov/ct2/show/record/NCT02847286; last access date January 18, 2019.]Search in Google Scholar
[58. V. Jespers, C. Noestlinger and K. K. Ariën, Designing microbicides against HIV: innovative rings for young women urgently needed, Future Virol. 12 (2017) 45–48; https://doi.org/10.2217/fvl-2016-013510.2217/fvl-2016-0135]Search in Google Scholar
[59. K. Bunge, L. Levy, D. Szydlo, J. Zhang, A. Gaur, D. Reirden, K. Mayer, D. Futterman, C. Hoesley, S. Hillier, M. Marzinke, C. Dezzutti, C. Wilson, L. Soto-Torres, B. Kapogiannis, A. Nel, K. Squires, and MTN-023/IPM 030 protocol team, Safety and acceptability trial of the dapivirine vaginal ring in U.S. adolescents, The 9th IAS Conference on HIV Science (IAS 2017), July 23-26, 2017, Paris (France); http://programme.ias2017.org/Abstract/Abstract/5540; last access date January 27, 2019.]Search in Google Scholar
[60. L. Noguchi, R. Beigi, J. Biggio, M. Marzinke, C. Kelly, K. Bunge, R. Scheckter, J. Piper, S. Hillier, A. Nel and C. Hendrix, Breast milk dapivirine pharmacokinetics, estimated infant exposure, and safety during dapivirine intravaginal ring use among lactating women, Am. J. Obstet. Gynecol. 217 (2017) 717–717; https://doi.org/10.1016/j.ajog.2017.08.08910.1016/j.ajog.2017.08.089]Search in Google Scholar
[61. P. Spence, A. Nel, N. van Niekerk, T. Derrick, S. Wilder and B. Devlin, Post-use assay of vaginal rings (VRs) as a potential measure of clinical trial adherence, J. Pharm. Biomed. Anal.125 (2016) 94–100; https://doi.org/10.1016/j.jpba.2016.03.02310.1016/j.jpba.2016.03.023487360127016673]Search in Google Scholar
[62. Trial to assess the continued safety of and adherence to a vaginal ring containing dapivirine in women; https://clinicaltrials.gov/ct2/show/record/NCT02858037?term=MTN-025&rank=1&view=record; last access date January 27, 2019.]Search in Google Scholar
[63. To assess continued safety of and adherence to the dapivirine (25 mg) vaginal ring-004 in healthy, HIV-negative Women; https://clinicaltrials.gov/ct2/show/NCT02862171?term=IPM+032&rank=1; last access date January 27, 2019.]Search in Google Scholar
[64. J. Baeten and C. Celum, HIV Prevention at CROI 2018 and PrEP updates on PrEP - disparities; current & future; delivery/use/barriers; women, transmission clusters, Conference on Retroviruses and Opportunistic Infections, Boston (MA), USA, March 4–7, 2018; http://www.natap.org/2018/CROI/croi_188.htm; last access date January 27, 2019.]Search in Google Scholar
[65. R. K. Malcolm, K. L. Edwards, P. Kiser, J. Romano and T. J. Smith, Advances in microbicide vaginal rings, Antiviral Res.88 (2010) S30–S39; https://doi.org/10.1016/j.antiviral.2010.09.00310.1016/j.antiviral.2010.09.00321109066]Search in Google Scholar
[66. The quatro study: Acceptability study of (placebo) vaginal delivery forms for preventing HIV and unintended pregnancy; https://clinicaltrials.gov/ct2/show/NCT02602366; last access date January 18, 2019.]Search in Google Scholar
[67. T. A. Jacot, M. R. Clark, O. E. Adedipe, S. Godbout, A. G. Peele, S Ju, J. L. Schwartz, A. R. Thurman and G. F. Doncel, Development and clinical assessment of new objective adherence markers for four microbicide delivery systems used in HIV prevention studies, Clin. Transl. Med.7 (2018) 37–37; https://doi.org/10.1186/s40169-018-0213-610.1186/s40169-018-0213-6621999830402770]Search in Google Scholar
[68. K. E. Bunge, C. S. Dezzutti, L. C. Rohan, C. W. Hendrix, M. A. Marzinke, N. Richardson-Harman, B. J. Moncla, B. Devlin, L. A. Meyn, H. M. Spiegel and S. L. Hillier, A phase 1 trial to assess the safety, acceptability, pharmacokinetics, and pharmacodynamics of a novel dapivirine vaginal film, J. Acquir. Immune Defic. Syndr.71 (2016) 498–505; https://doi.org/10.1097/QAI.000000000000089710.1097/QAI.0000000000000897504083026565716]Search in Google Scholar
[69. J. A. Robinson, M. A. Marzinke, R. P. Bakshi, E. J. Fuchs, C. L. Radebaugh, W. Aung, H. M. Spiegel, J. S. Coleman, L. C. Rohan and C. W. Hendrix, Comparison of dapivirine vaginal gel and film formulation pharmacokinetics and pharmacodynamics (FAME 02B), AIDS Res. Hum. Retroviruses33 (2017) 339–346; https://doi.org/10.1089/AID.2016.004010.1089/aid.2016.0040]Search in Google Scholar
[70. H. Agashe, M. Hu and L. Rohan, Formulation and delivery of microbicides, Curr. HIV Res.10 (2012) 88–96; https://doi.org/10.2174/15701621279930459910.2174/15701621279930459922264050]Search in Google Scholar
[71. Study of UC-781 vaginal microbicide; https://clinicaltrials.gov/ct2/show/record/NCT00132444?term=NCT00132444&rank=1; last access date January 18, 2019.]Search in Google Scholar
[72. Phase I study of safety and persistence of UC-781 vaginal microbicide; https://clinicaltrials.gov/ct2/show/NCT00441909?term=NCT00441909&rank=1; last access date January 21, 2019.]Search in Google Scholar
[73. K. Bunge, I. Macio, L. Meyn, L. Noguchi, M. A. Parniak, J. L. Schwartz, B. Moncla and S. Hillier, The safety, persistence, and acceptability of an antiretroviral microbicide candidate UC781, J. Acquir. Immune Defic. Syndr.60 (2012) 337–343; https://doi.org/10.1097/QAI.0b013e318257591410.1097/QAI.0b013e318257591422495787]Search in Google Scholar
[74. Safety study of UC-781 vaginal microbicide; https://clinicaltrials.gov/ct2/show/NCT00446979?term=NCT00446979&rank=1; last access date January 21, 2019.]Search in Google Scholar
[75. R. E. Haaland, T. Evans-Strickfaden, A. Holder, C. P. Pau, J. M. McNicholl, C. Chaikummao, W. Chonwattana and C. E. Hart, UC781 microbicide gel retains anti-HIV activity in cervicovaginal lavage fluids collected following twice-daily vaginal application, Antimicrob. Agents Chemother.56 (2012) 3592–3596; https://doi.org/10.1128/AAC.00452-1210.1128/AAC.00452-12339339822508307]Search in Google Scholar
[76. M. J. Keller, P. M. Mesquita, M. A. Marzinke, R. Teller, L. Espinoza, J. M. Atrio, Y. Lo, B. Frank, S. Srinivasan, D. N. Fredricks, L. Rabe, P. L. Anderson, C. W. Hendrix, P. F. Kiser and B. C. Herold, A phase 1 randomized placebo-controlled safety and pharmacokinetic trial of a tenofovir disoproxil fumarate vaginal ring, AIDS30 (2016) 743–751; https://doi.org/10.1097/QAD.000000000000097910.1097/QAD.0000000000000979476757926605514]Search in Google Scholar
[77. O. Mizenina, M. Hsu, N. Jean-Pierre, M. Aravantinou, K. Levendosky, G. Paglini, T. M. Zydowsky, M. Robbiani and J. A. Fernández-Romero, MIV-150 and zinc acetate combination provides potent and broad activity against HIV-1, Drug Deliv. Transl. Res.7 (2017) 859–866; https://doi.org/10.1007/s13346-017-0421-410.1007/s13346-017-0421-428812250]Search in Google Scholar
[78. B. A. Friedland, C. J. Hoesley, M. Plagianos, E. Hoskin, S. Zhang, N. Teleshova, M. Alami, L. Novak, K. R. Kleinbeck, L. L. Katzen, T. M. Zydowsky, J. A. Fernández-Romero and G. W. Creasy, First-in-human trial of MIV-150 and zinc acetate coformulated in a carrageenan gel: safety, pharmacokinetics, acceptability, adherence, and pharmacodynamics, J. Acquir. Immune Defic. Syndr. 73 (2016) 489–496; https://doi.org/10.1097/QAI.000000000000113610.1097/QAI.0000000000001136517284827437826]Search in Google Scholar
[79. Evaluate the safety and assess local and systemic PK of DS003 vaginal tablets administered to healthy HIV-negative women; https://clinicaltrials.gov/ct2/show/NCT02877979?term=IPM+042&rank=1; last access date January 21, 2019.]Search in Google Scholar
[80. S. M. Fetherston, P. Boyd, C. F. McCoy, M. C. McBride, K. L. Edwards, S. Ampofo and R. K. Malcolm, A silicone elastomer vaginal ring for HIV prevention containing two microbicides with different mechanisms of action, Eur. J. Pharm. Sci.48 (2013) 406–415; https://doi.org/10.1016/j.ejps.2012.12.00210.1016/j.ejps.2012.12.00223266465]Search in Google Scholar
[81. M. R. Clark, M. M. Peet, S. Davis, G. F. Doncel and D. R. Friend, Evaluation of rapidly disintegrating vaginal tablets of tenofovir, emtricitabine and their combination for HIV-1 prevention, Pharmaceutics6 (2014) 616–631; https://doi.org/10.3390/pharmaceutics604061610.3390/pharmaceutics6040616427913625494201]Search in Google Scholar
[82. Safety, pharmacokinetics, pharmacodynamics, and disintegration time of vaginal tablets containing tenofovir and/or emtricitabine; https://clinicaltrials.gov/ct2/show/study/NCT01694407?term=emtricitabine+vaginal&rank=2; last access date January 27, 2019.]Search in Google Scholar
[83. B. A. Chen, L. Panther, M. A. Marzinke, C. W. Hendrix, C. J. Hoesley, A. van der Straten, M. J. Husnik, L. Soto-Torres, A. Nel, S. Johnson, N. Richardson-Harman, L. K. Rabe and C. S. Dezzutti, Phase 1 safety, pharmacokinetics, and pharmacodynamics of dapivirine and maraviroc vaginal rings: a double-blind randomized trial, J. Acquir. Immune Defic. Syndr.70 (2015) 242–249; https://doi.org/10.1097/QAI.000000000000070210.1097/QAI.0000000000000702460758726034880]Search in Google Scholar
[84. Safety and pharmacokinetics of intravaginal rings containing vicriviroc (MK-4176) and/or MK-2048; https://clinicaltrials.gov/ct2/show/NCT02356302?term=MTN-027&rank=1; last access date January 21, 2019.]Search in Google Scholar
[85. C. J. Hoesley, B. A. Chen, P. L. Anderson, C. S. Dezzutti, J. Strizki, C. Sprinkle, F. Heard, J. Bauermeister, W. Hall, C. Jacobson, J. Berthiaume, A. Mayo, H. Gundacker, N. Richardson-Harman and J. Piper, Microbicide Trials Network 027 Study Team, Phase 1 safety and pharmacokinetics study of MK-2048/vicriviroc (MK-4176)/MK-2048A intravaginal rings, Clin. Infect. Dis., Oct 2018 (in press); https://doi.org/10.1093/cid/ciy65310.1093/cid/ciy653642407530289435]Search in Google Scholar
[86. Safety and pharmacokinetic study of hiv prophylaxis using antiretroviral intravaginal rings in healthy women; https://clinicaltrials.gov/ct2/show/NCT02431273?term=NCT02431273&rank=1; last access date January 27, 2019.]Search in Google Scholar
[87. K. L. Vincent, J. A. Moss, M. A. Marzinke, C. W. Hendrix, P. A. Anton, R. B. Pyles, K. M. Guthrie, L. Dawson, T. J. Olive, I. Butkyavichene, S. A. Churchman, J. M. Cortez Jr, R. Fanter, M. Gunawardana, C. S. Miller, F. Yang, R. K. Rosen, S. E. Vargas and M. M. Baum, Safety and pharmacokinetics of single, dual, and triple antiretroviral drug formulations delivered by pod-intravaginal rings designed for HIV-1 prevention: A phase I trial, PLOS Med.15 (2018) e1002655; https://doi.org/10.1371/journal.pmed.100265510.1371/journal.pmed.1002655616185230265679]Search in Google Scholar
[88. R. Sitruk-Ware, A. Nath and D. R. Mishell, Jr., Contraception technology: past, present and future. Contraception87 (2013) 319–330; https://doi.org/10.1016/j.contraception.2012.08.00210.1016/j.contraception.2012.08.002353062722995540]Search in Google Scholar
[89. J. T. Clark, M. R. Clark, N. B. Shelke, T. J. Johnson, E. M. Smith, A. K. Andreasen, J. S. Nebeker, J. Fabian, D. R. Friend and P. F. Kiser, Engineering a segmented dual-reservoir polyurethane intravaginal ring for simultaneous prevention of HIV transmission and unwanted pregnancy, PLoS ONE9 (2014) e88509; https://doi.org/10.1371/journal.pone.008850910.1371/journal.pone.0088509394371824599325]Search in Google Scholar
[90. A. R. Thurman, J. L. Schwartz, V. Brache, M. R. Clark, T. McCormick, N. Chandra, M. A. Marzinke, F. Z. Stanczyk, C. S. Dezzutti, S. L. Hillier, B. C. Herold, R. Fichorova, S. N. Asin, C. Rollenhagen, D. Weiner, P. Kiser and G. F. Doncel, Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women, PLOS ONE13 e0199778; https://doi.org/10.1371/journal.pone.019977810.1371/journal.pone.0199778602323829953547]Search in Google Scholar
[91. PK and safety study of vaginal rings containing dapivirine and levonorgestrel (DAP/LNG); https://clinicaltrials.gov/ct2/show/NCT02855346?term=MTN-030%2FIPM+041&rank=1; last access date January 21, 2019.]Search in Google Scholar
[92. R. D. Cranston, J. R. Lama, B. A. Richardson, A. Carballo-Diéguez, R. P. Kunjara Na Ayudhya, K. Liu, K. B. Patterson, C. S. Leu, B. Galaska, C. E. Jacobson, U. M. Parikh, M. A. Marzinke, C. W. Hendrix, S. Johnson, J. M. Piper, C. Grossman, K. S. Ho, J. Lucas, J. Pickett, L. G. Bekker, S. Chariyalertsak, A. Chitwarakorn, P. Gonzales, T. H. Holtz, A. Y. Liu, K. H. Mayer, C. Zorrilla, J. L. Schwartz, J. Rooney, I. McGowan and MTN-017 protocol team, A rectal phase 2 extended safety and acceptability study of tenofovir reduced-glycerin 1% gel, Clin. Infect. Dis. 64 (2017) 614–620; https://doi.org/10.1093/cid/ciw83210.1093/cid/ciw832585051827986684]Search in Google Scholar
[93. A. Carballo-Diéguez, I. C. Balán, W. Brown, R. Giguere, C. Dolezal, C. Leu, M. A. Marzinke, C. W. Hendrix, J. M. Piper, B. A. Richardson, C.Grossman, S. Johnson, K. Gomez, S. Horn, R. P. K. Na Ayudhya, K. Patterson, C. Jacobson, L. Bekker, S. Chariyalertsak, A. Chitwarakorn, P. Gonzales, T. H. Holtz, A. Liu, K. H. Mayer, C. Zorrilla, J. Lama, I. McGowan and R. D. Cranston, 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 ONE12 e0181607; https://doi.org/10.1371/journal.pone.018160710.1371/journal.pone.0181607553150328750059]Search in Google Scholar
[94. P. A. Anton, T. Saunders, J. Elliott, E. Khanukhova, R. Dennis, A. Adler, G. Cortina, K. Tanner, J. Boscardin, W. G. Cumberland, Y. Zhou, A. Ventuneac, A. Carballo-Diéguez, L. Rabe, T. McCormick, H. Gabelnick, C. Mauck and I. McGowan, First phase 1 double-blind, placebo-controlled, randomized rectal microbicide trial using UC781 gel with a novel index of ex vivo efficacy, PLoS ONE6 (2011) e23243; https://doi.org/10.1371/journal.pone.002324310.1371/journal.pone.0023243318216021969851]Search in Google Scholar
[95. Safety and pharmacokinetic study of oral maraviroc and maraviroc 1% gel in HIV-1 seronegative adults; https://clinicaltrials.gov/ct2/show/NCT02346084?term=NCT02346084&rank=1; last access date January 21, 2019.]Search in Google Scholar