301
Views
7
CrossRef citations to date
0
Altmetric
Review

Vaginal multipurpose prevention technologies: promising approaches for enhancing women’s sexual and reproductive health

, , ORCID Icon, ORCID Icon & ORCID Icon
Pages 379-393 | Received 29 Sep 2019, Accepted 07 Feb 2020, Published online: 17 Feb 2020

References

  • Glasier A, Gulmezoglu AM, Schmid GP, et al. Sexual and reproductive health: a matter of life and death. Lancet. 2006 Nov 4;368(9547):1595–1607.
  • UNAIDS. UNAIDS Data 2019. [cited 2019 Dec 3]. Available from: http://www.unaids.org/en/resources/documents/2019/2019-UNAIDS-data
  • World Health Organization. Report on global sexually transmitted infection surveillance. 2018 [cited 2019 Dec 10]. Avaliable from: https://www.who.int/reproductivehealth/publications/stis-surveillance-2018/en/
  • Rowley J, Vander Hoorn S, Korenromp E, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ. 2019 Aug 1;97(8):548–62P.
  • GBD 2017. Disease and injury incidence and prevalence collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the global burden of disease study 2017. Lancet. 2018 Nov 10;392(10159):1789–1858.
  • GBD 2017. Causes of death collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the global burden of disease study 2017. Lancet. 2018 Nov 10;392(10159):1736–1788.
  • Bearak J, Popinchalk A, Alkema L, et al. Global, regional, and subregional trends in unintended pregnancy and its outcomes from 1990 to 2014: estimates from a Bayesian hierarchical model. Lancet Glob Health. 2018 Apr;6(4):e380–e89.
  • Darroch JE, Singh S. Trends in contraceptive need and use in developing countries in 2003, 2008, and 2012: an analysis of national surveys. Lancet. 2013 May 18;381(9879):1756–1762.
  • Quaife M, Eakle R, Cabrera Escobar MA, et al. Divergent preferences for HIV prevention: a discrete choice experiment for multipurpose HIV prevention products in South Africa. Med Decis Making. 2018;38(1):120–133.
  • Weinrib R, Minnis A, Agot K, et al. End-users’ product preference across three multipurpose prevention technology delivery forms: baseline results from young women in Kenya and South Africa. AIDS Behav. 2018 Jan;22(1):133–145.
  • Minnis AM, Browne EN, Boeri M, et al. Young women’s stated preferences for biomedical HIV prevention: results of a discrete choice experiment in Kenya and South Africa. J Acquir Immune Defic Syndr. 2019 Apr 1;80(4):394–403.
  • Hynes JS, Sheth AN, Lathrop E, et al. Preferred product attributes of potential multipurpose prevention technologies for unintended pregnancy and sexually transmitted infections or HIV among U.S. women. J Womens Health (Larchmt). 2019 May;28(5):665–672.
  • Quaife M, Terris-Prestholt F, Eakle R, et al. The cost-effectiveness of multi-purpose HIV and pregnancy prevention technologies in South Africa. J Int AIDS Soc. 2018;21(3):Mar.
  • Population Council. Developing an oral contraceptive and HIV-prevention method, in a single pill. [cited 2019 Dec 12]. Available from: https://www.popcouncil.org/research/developing-an-oral-contraceptive-and-hiv-prevention-method-in-a-single-pill
  • Rajoli R, Clark A, Rein-Weston A, et al. In silico design of a microarray patch as a multipurpose prevention technology [Abstract]. Rev Antivir Ther Infect Dis. 2019;4:4.
  • RTI International. New multipurpose device to help prevent HIV and pregnancy. [cited 2019 Dec 6]. Available from: https://www.rti.org/news/new-multipurpose-device-help-prevent-hiv-and-pregnancy
  • Clark JT, Clark MR, Shelke NB, et al. Engineering a segmented dual-reservoir polyurethane intravaginal ring for simultaneous prevention of HIV transmission and unwanted pregnancy. PLoS One. 2014;9(3):e88509.
  • Dallal Bashi YH, McCoy CF, Murphy DJ, et al. Towards a dapivirine and levonorgestrel multipurpose vaginal ring: investigations into the reaction between levonorgestrel and addition-cure silicone elastomers. Int J Pharm. 2019 Oct;5(569):118574.
  • Calenda G, Villegas G, Barnable P, et al. MZC gel inhibits SHIV-RT and HSV-2 in macaque vaginal mucosa and SHIV-RT in rectal mucosa. J Acquir Immune Defic Syndr. 2017 Mar 1;74(3):e67–e74.
  • Brady M, Tolley E. Aligning product development and user perspectives: social-behavioural dimensions of multipurpose prevention technologies. BJOG. 2014 Oct;121(Suppl 5):70–78.
  • Barnhart KT, Izquierdo A, Pretorius ES, et al. Baseline dimensions of the human vagina. Hum Reprod. 2006 Jun;21(6):1618–1622.
  • Moore C, Daneshgari F. Vaginal anatomy for the pelvic surgeon. In: Zimmern PE, Norton PA, Haab F, et al., editors. Vaginal surgery for incontinence and prolapse. London: Springer; 2006. p. 3–10.
  • Squier CA, Mantz MJ, Schlievert PM, et al. Porcine vagina ex vivo as a model for studying permeability and pathogenesis in mucosa. J Pharm Sci. 2008 Jan;97(1):9–21.
  • Richter K, Frick H. Anatomy of the visceral fascia of the pelvis from the didactic viewpoint [Article in German]. Geburtshilfe Frauenheilkd. 1985 May;45(5):282–287.
  • Pendergrass PB, Reeves CA, Belovicz MW, et al. The shape and dimensions of the human vagina as seen in three-dimensional vinyl polysiloxane casts. Gynecol Obstet Invest. 1996;42(3):178–182.
  • das Neves J. Vaginal delivery of biopharmaceuticals. In: das Neves J, Sarmento B, editors. Mucosal delivery of biopharmaceuticals: biology, challenges and strategies. New York, NY: Springer; 2014. p. 261–280.
  • Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011 Mar 15;108(Suppl 1):4680–4687.
  • das Neves J, Amiji M, Sarmento B. Mucoadhesive nanosystems for vaginal microbicide development: friend or foe?. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2011 Jul 3;3(4):389–399.
  • Lai SK, Wang YY, Hida K, et al. Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses. Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):598–603.
  • Olmsted SS, Padgett JL, Yudin AI, et al. Diffusion of macromolecules and virus-like particles in human cervical mucus. Biophys J. 2001 Oct;81(4):1930–1937.
  • Boskey ER, Cone RA, Whaley KJ, et al. Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. Hum Reprod. 2001 Sep;16(9):1809–1813.
  • Farage M, Maibach H. Lifetime changes in the vulva and vagina. Arch Gynecol Obstet. 2006 Jan;273(4):195–202.
  • Mwatelah R, McKinnon LR, Baxter C, et al. Mechanisms of sexually transmitted infection-induced inflammation in women: implications for HIV risk. J Int AIDS Soc. 2019 Aug;22(Suppl 6):e25346.
  • Thurman AR, Doncel GF. Innate immunity and inflammatory response to Trichomonas vaginalis and bacterial vaginosis: relationship to HIV acquisition. Am J Reprod Immunol. 2011 Feb;65(2):89–98.
  • das Neves J, Palmeira-de-Oliveira R, Palmeira-de-Oliveira A, et al. Vaginal mucosa and drug delivery. In: Khutoryanskiy VV, editor. Mucoadhesive materials and drug delivery systems. Chichester, UK: Wiley; 2014. p. 99–131.
  • Blostein F, Levin-Sparenberg E, Wagner J, et al. Recurrent vulvovaginal candidiasis. Ann Epidemiol. 2017 Sep;27(9):575–82 e3.
  • Guirguis-Blake JM, Henderson JT, Perdue LA. Periodic screening pelvic examination: evidence report and systematic review for the US preventive services task force. JAMA. 2017 Mar 7;317(9):954–966.
  • Hussain A, Ahsan F. The vagina as a route for systemic drug delivery. J Control Release. 2005 Mar 21;103(2):301–313.
  • Woodsong C, Holt JD. Acceptability and preferences for vaginal dosage forms intended for prevention of HIV or HIV and pregnancy. Adv Drug Deliv Rev. 2015 Feb 19;15(92):146–154.
  • Hardy E, de Padua KS, Jimenez AL, et al. Women’s preferences for vaginal antimicrobial contraceptives. II. Preferred characteristics according to women’s age and socioeconomic status. Contraception. 1998 Oct;58(4):239–244.
  • Coggins C, Elias CJ, Atisook R, et al. Women’s preferences regarding the formulation of over-the-counter vaginal spermicides. AIDS. 1998 Jul 30;12(11):1389–1391.
  • Hardy E, de Padua KS, Osis MJ, et al. Women’s preferences for vaginal antimicrobial contraceptives. IV. Attributes of a formulation that would protect from STD/AIDS. Contraception. 1998 Oct;58(4):251–255.
  • Braunstein S. van de Wijgert J. Preferences and practices related to vaginal lubrication: implications for microbicide acceptability and clinical testing. J Womens Health. 2005 Jun;14(5):424–433.
  • Harrison PF, Hemmerling A, Romano J, et al. Developing multipurpose reproductive health technologies: an integrated strategy. AIDS Res Treat. 2013;2013:790154.
  • Baeten JM, Hendrix CW, Hillier SL. Topical microbicides in HIV prevention: state of the promise. Annu Rev Med. 2019 Oct 15. DOI:10.1146/annurev-med-090518-3731.
  • Stein ZA. HIV prevention: the need for methods women can use. Am J Public Health. 1990 Apr;80(4):460–462.
  • Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168–1174.
  • Delany-Moretlwe S, Lombard C, Baron D, et al. Tenofovir 1% vaginal gel for prevention of HIV-1 infection in women in South Africa (FACTS-001): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2018 Nov;18(11):1241–1250.
  • Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015 Feb 5;372(6):509–518.
  • Malcolm RK, Boyd PJ, McCoy CF, et al. Microbicide vaginal rings: technological challenges and clinical development. Adv Drug Deliv Rev. 2016 Aug;1(103):33–56.
  • Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N Engl J Med. 2016 Dec;375(22):2121–2132.
  • Nel A, van Niekerk N, Kapiga S, et al. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N Engl J Med. 2016 Dec;375(22):2133–2143.
  • Romano J, Manning J, Hemmerling A, et al. Prioritizing multipurpose prevention technology development and investments using a target product profile. Antiviral Res. 2013 Dec;100(Suppl):S32–8.
  • van de Wijgert JH, Morrison CS, Brown J, et al. Disentangling contributions of reproductive tract infections to HIV acquisition in African women. Sex Transm Dis. 2009 Jun;36(6):357–364.
  • van de Wijgert JH, Chirenje ZM, Iliff V, et al. Effect of intravaginal practices on the vaginal and cervical mucosa of Zimbabwean women. J Acquir Immune Defic Syndr. 2000 May 1;24(1):62–67.
  • Van Der Pol B, Kwok C, Pierre-Louis B, et al. Trichomonas vaginalis infection and human immunodeficiency virus acquisition in African women. J Infect Dis. 2008 Feb 15;197(4):548–554.
  • Higgins JA, Smith NK, Sanders SA, et al. Dual method use at last sexual encounter: a nationally representative, episode-level analysis of US men and women. Contraception. 2014 Oct;90(4):399–406.
  • Podaralla S, Alt C, Shankar GN. Formulation development and evaluation of innovative two-polymer (SR-2P) bioadhesive vaginal gel. AAPS PharmSciTech. 2014 Aug;15(4):928–938.
  • Ugaonkar SR, Wesenberg A, Wilk J, et al. A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy. J Control Release. 2015 Sep 10;213:57–68.
  • Smith JM, Moss JA, Srinivasan P, 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.
  • CONRAD. Safety, PK, and PD study of a vaginal insert containing TAF and EVG. Available from: https://clinicaltrials.gov/ct2/show/NCT03762772
  • LeafBio I Vaginal antibody safety trial: safety study of monoclonal antibodies to reduce the vaginal transmission of herpes simplex virus (HSV) and human immunodeficiency virus (HIV). Available from: https://clinicaltrials.gov/ct2/show/NCT02579083
  • Population Council. Safety, pharmacokinetics and acceptability of PC-1005 for vaginal use. Available from: https://clinicaltrials.gov/ct2/show/NCT02033109
  • Price CF, Tyssen D, Sonza S, et al. SPL7013 gel (VivaGel(R)) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans. PLoS One. 2011;6(9):e24095.
  • CONRAD. Safety and effectiveness of tenofovir gel in the prevention of human immunodeficiency virus (HIV-1) infection in women and the effects of tenofovir gel on the incidence of herpes simplex virus (HSV-2) infection. Available from: https://clinicaltrials.gov/ct2/show/NCT01386294
  • Pazol K, Kramer MR, Hogue CJ. Condoms for dual protection: patterns of use with highly effective contraceptive methods. 433021. 2010 Mar-Apr;125(2):208–217.
  • Davis KR, Weller SC. The effectiveness of condoms in reducing heterosexual transmission of HIV. Fam Plann Perspect. 1999 Nov-Dec;31(6):272–279.
  • Gallo MF, Grimes DA, Lopez LM, et al. Non-latex versus latex male condoms for contraception. Cochrane Database Syst Rev. 2006 Jan;25(1):CD003550.
  • Friend DR, Doncel GF. Combining prevention of HIV-1, other sexually transmitted infections and unintended pregnancies: development of dual-protection technologies. Antiviral Res. 2010 Dec;88(Suppl 1):S47–54.
  • Major I, Boyd P, Kilbourne-Brook M, et al. A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine. Contraception. 2013;88(1):58–66.
  • Mohammed Fayaz A, Ao Z, Girilal M, et al. Inactivation of microbial infectiousness by silver nanoparticles-coated condom: a new approach to inhibit HIV- and HSV-transmitted infection. Int J Nanomedicine. 2012;7:5007–5018.
  • Frezieres RG, Walsh T, Kilbourne-Brook M, et al. Couples’ acceptability of the SILCS diaphragm for microbicide delivery. Contraception. 2012 Jan;85(1):99–107.
  • Giguere R, Carballo-Dieguez A, Ventuneac A, et al. Variations in microbicide gel acceptability among young women in the USA and Puerto Rico. Cult Health Sex. 2012;14(2):151–166.
  • Gali Y, Delezay O, Brouwers J, et al. In vitro evaluation of viability, integrity and inflammation in genital epithelia upon exposure to pharmaceutical excipients and candidate microbicides. Antimicrob Agents Chemother. 2010 Oct 4;54(12):5105–5114.
  • Fernández-Romero JA, Teleshova N, Zydowsky TM, et al. Preclinical assessments of vaginal microbicide candidate safety and efficacy. Adv Drug Deliv Rev. 2015 Sep;15(92):27–38.
  • Veazey RS. Microbicide safety/efficacy studies in animals: macaques and small animal models. Curr Opin HIV AIDS. 2008 Sep;3(5):567–573.
  • Veazey RS, Shattock RJ, Klasse PJ, et al. Animal models for microbicide studies. Curr HIV Res. 2012 Jan 1;10(1):79–87.
  • Kizima L, Rodriguez A, Kenney J, et al. A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV. PLoS One. 2014;9(4):e94547.
  • Fichorova RN, Bajpai M, Chandra N, et al. Interleukin (IL)-1, IL-6, and IL-8 predict mucosal toxicity of vaginal microbicidal contraceptives. Biol Reprod. 2004 Sep;71(3):761–769.
  • Moss JA, Malone AM, Smith TJ, et al. Pharmacokinetics of a multipurpose pod-intravaginal ring simultaneously delivering five drugs in an ovine model. Antimicrob Agents Chemother. 2013 Aug;57(8):3994–3997.
  • Kreiss J, Ngugi E, Holmes K, et al. Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA. 1992 Jul 22–29;268(4):477–482.
  • Van Damme L, Ramjee G, Alary M, et al. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial. Lancet. 2002 Sep 28;360(9338):971–977.
  • Thurman AR, Schwartz JL, Brache V, et al. Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women. PLoS One. 2018;13(6):e0199778.
  • Achilles SL, Hendrix CW, Poloyac SM, et al. Safety and pharmacokinetics of dapivirine and levonorgestrel vaginal rings for multipurpose prevention of HIV and pregnancy [Abstract]. AIDS Res Hum Retroviruses. 2018;34(S1):46.
  • Lanham M, Wilcher R, Montgomery ET, et al. Engaging male partners in women’s microbicide use: evidence from clinical trials and implications for future research and microbicide introduction. J Int AIDS Soc. 2014;17(3 Suppl 2):19159.
  • Walwyn D, Maitshotlo B. Perspectives of traditional health practitioners on the use of microbicides for the prevention of HIV. Afr J Tradit Complement Altern Med. 2012;9(3 Suppl):24–26.
  • van der Straten A, Stadler J, Montgomery E, et al. Women’s experiences with oral and vaginal pre-exposure prophylaxis: the VOICE-C qualitative study in Johannesburg, South Africa. PLoS One. 2014;9(2):e89118.
  • Hoffman S, Morrow KM, Mantell JE, et al. Covert use, vaginal lubrication, and sexual pleasure: a qualitative study of urban U.S. women in a vaginal microbicide clinical trial. Arch Sex Behav. 2010 Jun;39(3):748–760.
  • Montgomery ET, van der Straten A, Chidanyika A, et al. The importance of male partner involvement for women’s acceptability and adherence to female-initiated HIV prevention methods in Zimbabwe. AIDS Behav. 2011 Jul;15(5):959–969.
  • Mngadi KT, Maarschalk S, Grobler AC, et al. Disclosure of microbicide gel use to sexual partners: influence on adherence in the CAPRISA 004 trial. AIDS Behav. 2014 May;18(5):849–854.
  • Friend DR. Drug delivery in multiple indication (multipurpose) prevention technologies: systems to prevent HIV-1 transmission and unintended pregnancies or HSV-2 transmission. Expert Opin Drug Deliv. 2012 Apr;9(4):417–427.
  • Friend DR, Clark JT, Kiser PF, et al. Multipurpose prevention technologies: products in development. Antiviral Res. 2013 Dec;100(Suppl):S39–47.
  • Friend DR. An update on multipurpose prevention technologies for the prevention of HIV transmission and pregnancy. Expert Opin Drug Deliv. 2016;13(4):533–545.
  • Fernández-Romero JA, Deal C, Herold BC, et al. Multipurpose prevention technologies: the future of HIV and STI protection. Trends Microbiol. 2015 Jul;23(7):429–436.
  • Woodsong C, Holt J, Devlin B, et al. Current status of multipurpose prevention technology (MPT) development. Curr Obstet Gynecol Rep. 2015;4(1):43–52.
  • Valenta C. The use of mucoadhesive polymers in vaginal delivery. Adv Drug Deliv Rev. 2005 Nov 3;57(11):1692–1712.
  • McConville C, Major I, Devlin B, et al. Development of a multi-layered vaginal tablet containing dapivirine, levonorgestrel and acyclovir for use as a multipurpose prevention technology. Eur J Pharm Biopharm. 2016 Jul;104:171–179.
  • Lal M, Lai M, Ugaonkar S, et al. Development of a vaginal fast-dissolving insert combining griffithsin and carrageenan for potential use against sexually transmitted infections. J Pharm Sci. 2018 Oct;107(10):2601–2610.
  • Levendosky K, Mizenina O, Martinelli E, et al. Griffithsin and carrageenan combination to target herpes simplex virus 2 and human papillomavirus. Antimicrob Agents Chemother. 2015 Dec;59(12):7290–7298.
  • Nader-Macías ME, Juárez Tomás MS. Profiles and technological requirements of urogenital probiotics. Adv Drug Deliv Rev. 2015 Sep;15(92):84–104.
  • Sánchez MT, Ruiz MA, Castán H, et al. A novel double-layer mucoadhesive tablet containing probiotic strain for vaginal administration: design, development and technological evaluation. Eur J Pharm Sci. 2018 Jan;15(112):63–70.
  • Machado RM, Palmeira-de-Oliveira A, Martinez-de-Oliveira J, et al. Vaginal films for drug delivery. J Pharm Sci. 2013 May 6;102(7):2069–2081.
  • Cautela MP, Moshe H, Sosnik A, et al. Composite films for vaginal delivery of tenofovir disoproxil fumarate and emtricitabine. Eur J Pharm Biopharm. 2019 2;Feb(138):3–10.
  • Cunha-Reis C, Machado A, Barreiros L, et al. Nanoparticles-in-film for the combined vaginal delivery of anti-HIV microbicide drugs. J Control Release. 2016 Sep;21(243):43–53.
  • Griffin JB, Ridgeway K, Montgomery E, et al. Vaginal ring acceptability and related preferences among women in low- and middle-income countries: a systematic review and narrative synthesis. PLoS One. 2019;14(11):e0224898.
  • Johnson TJ, Gupta KM, Fabian J, et al. Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir. Eur J Pharm Sci. 2010 Feb 19;39(4):203–212.
  • Boyd P, Fetherston SM, McCoy CF, et al. Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel. Int J Pharm. 2016 Sep 10;511(1):619–629.
  • Moss JA, Malone AM, Smith TJ, et al. Simultaneous delivery of tenofovir and acyclovir via an intravaginal ring. Antimicrob Agents Chemother. 2012 Feb;56(2):875–882.
  • das Neves J, Bahia MF. Gels as vaginal drug delivery systems. Int J Pharm. 2006 Aug 2;318(1–2):1–14.
  • Guthrie KM, Dunsiger S, Vargas SE, et al. Perceptibility and the “choice experience”: user sensory perceptions and experiences inform vaginal prevention product design. AIDS Res Hum Retroviruses. 2016;32(10–11):1022–1030.
  • Duby Z, Mensch B, Hartmann M, et al. Achieving the optimal vaginal state: using vaginal products and study gels in Uganda, Zimbabwe, and South Africa. Int J Sex Health. 2017;29(3):247–257.
  • Abdool Karim SS, Abdool Karim Q, Kharsany AB, et al. Tenofovir gel for the prevention of herpes simplex virus type 2 infection. N Engl J Med. 2015 Aug 6;373(6):530–539.
  • Friedland BA, Hoesley CJ, Plagianos M, et al. 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. 2016 Dec 15;73(5):489–496.
  • Nelson AL. An overview of properties of Amphora (Acidform) contraceptive vaginal gel. Expert Opin Drug Saf. 2018 Sep;17(9):935–943.
  • Wang L, Sassi AB, Patton D, et al. Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention. Drug Dev Ind Pharm. 2012 Aug;38(8):995–1007.
  • Lakshmi YS, Kumar P, Kishore G, et al. Triple combination MPT vaginal microbicide using curcumin and efavirenz loaded lactoferrin nanoparticles. Sci Rep. 2016 May;6(6):25479.
  • Lazniewska J, Milowska K, Gabryelak T. Dendrimers – revolutionary drugs for infectious diseases. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2012 Sep-Oct;4(5):469–491.
  • McCarthy TD, Karellas P, Henderson SA, et al. Dendrimers as drugs: discovery and preclinical and clinical development of dendrimer-based microbicides for HIV and STI prevention. Mol Pharm. 2005 Jul-Aug;2(4):312–318.
  • McGowan I, Gomez K, Bruder K, et al. Phase 1 randomized trial of the vaginal safety and acceptability of SPL7013 gel (VivaGel) in sexually active young women (MTN-004). AIDS. 2011 May 15;25(8):1057–1064.
  • Moscicki AB, Kaul R, Ma Y, et al. Measurement of mucosal biomarkers in a phase 1 trial of intravaginal 3% StarPharma LTD 7013 gel (VivaGel) to assess expanded safety. J Acquir Immune Defic Syndr. 2012 Feb 1;59(2):134–140.
  • Sepúlveda-Crespo D, Ceña-Díez R, Jiménez JL, et al. Mechanistic studies of viral entry: an overview of dendrimer-based microbicides as entry inhibitors against both HIV and HSV-2 overlapped infections. Med Res Rev. 2017 Aug 12;37(1):149–179.
  • Cena-Diez R, Martin-Moreno A, de la Mata FJ, et al. G1-S4 or G2-S16 carbosilane dendrimer in combination with Platycodin D as a promising vaginal microbicide candidate with contraceptive activity. Int J Nanomedicine. 2019;14:2371–2381.
  • Laborde ND, Leslie J, Krogstad E, et al. Perceptions of the “Fabric” – an exploratory study of a novel multi-purpose technology among women in Sub Saharan Africa. PLoS One. 2018;13(10):e0204821.
  • Blakney AK, Krogstad EA, Jiang YH, et al. Delivery of multipurpose prevention drug combinations from electrospun nanofibers using composite microarchitectures. Int J Nanomedicine. 2014;9:2967–2978.
  • Chou SF, Carson D, Woodrow KA. Current strategies for sustaining drug release from electrospun nanofibers. J Control Release. 2015 Dec 28;220(Pt B):584–591.
  • Ball C, Krogstad E, Chaowanachan T, et al. Drug-eluting fibers for HIV-1 inhibition and contraception. PLoS One. 2012;7(11):e49792.
  • Tyo KM, Vuong HR, Malik DA, et al. Multipurpose tenofovir disoproxil fumarate electrospun fibers for the prevention of HIV-1 and HSV-2 infections in vitro. Int J Pharm. 2017 Oct 5;531(1):118–133.
  • Alukda D, Sturgis T, Youan BB. Formulation of tenofovir-loaded functionalized solid lipid nanoparticles intended for HIV prevention. J Pharm Sci. 2011 Aug;100(8):3345–3356.
  • Zhang T, Sturgis TF, Youan BB. pH-responsive nanoparticles releasing tenofovir intended for the prevention of HIV transmission. Eur J Pharm Biopharm. 2011 Nov;79(3):526–536.
  • Tevi-Benissan C, Belec L, Levy M, et al. In vivo semen-associated pH neutralization of cervicovaginal secretions. Clin Diagn Lab Immunol. 1997 May;4(3):367–374.
  • Lara HH, Ayala-Nunez NV, Ixtepan-Turrent L, et al. Mode of antiviral action of silver nanoparticles against HIV-1. J Nanobiotechnology. 2010;8:1.
  • Vijayakumar S, Ganesan S. Gold nanoparticles as an HIV entry inhibitor. Curr HIV Res. 2012 Dec;10(8):643–646.
  • Baram-Pinto D, Shukla S, Gedanken A, et al. Inhibition of HSV-1 attachment, entry, and cell-to-cell spread by functionalized multivalent gold nanoparticles. Small. 2010 May 7;6(9):1044–1050.
  • Etemadzade M, Ghamarypour A, Zabihollahi R, et al. Synthesis and evaluation of antiviral activities of novel sonochemical silver nanorods against HIV and HSV viruses. Asian Pacific J Trop Dis. 2016;6(11):854–858.
  • U.S. Food & Drug Administration. Guidance for industry. vaginal microbicides: development for the prevention of HIV infection. Silver Spring, MD; 2014 [cited 2019 Feb 15]. Available from: https://www.fda.gov/downloads/drugs/guidances/ucm328842.pdf
  • U.S. Food and Drug Administration. Guidance for the development of vaginal contraceptive drugs (NDA). Silver Spring, MD; 1998[cited 2019 Feb 15]. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-development-vaginal-contraceptive-drugs-nda
  • Kis O, Robillard K, Chan GN, et al. The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters. Trends Pharmacol Sci. 2010 Jan;31(1):22–35.
  • Nardi R, Arterburn L, Carlton L. Developing regulatory strategy for microbicides. Curr Top Microbiol Immunol. 2014;383:137–152.
  • Steytner J What’s next in the dapivirine ring licensure program? MTN 2019 Regional Meeting, Cape Town, South Africa. [cited 2019 Dec 10]. Available from: https://mtnstopshiv.org/sites/default/files/steytler-mtn_meeting_presentation_1.0_09_sep2019.pdf

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.