1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Medicine
  4. Volume 71, 2020
  5. Article

Annual Review of Medicine

Volume 71, 2020

Topical Microbicides in HIV Prevention: State of the Promise

Abstract

HIV topical microbicides are products with anti-HIV activity, generally incorporating a direct-acting antiretroviral agent, that when applied to the vagina or rectum have the potential to prevent the sexual acquisition of HIV in women and men. Topical microbicides may meet the prevention needs of individuals and groups for whom oral daily forms of pre-exposure prophylaxis (PrEP) have not been acceptable. Microbicides can provide personal control over HIV prevention and offer the possibility of discreet use, qualities that may be particularly important for receptive partners in sexual relationships such as women and transgender women and men, who together account for the clear majority of new HIV infections worldwide. Although the promise of such a product emerged nearly three decades ago, proof of concept has been demonstrated only within the last decade. A robust pipeline of microbicidal gels, films, inserts, and rings has been evaluated in multiple studies among at-risk women and men, and refinement of products for ease of use, reversibility, and high safety is the priority for the field.

Keyword(s): dapivirine vaginal ring, HIV, HIV prevention, microbicide
Loading

Article metrics loading...

/content/journals/10.1146/annurev-med-090518-093731
2020-01-27
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/med/71/1/annurev-med-090518-093731.html?itemId=/content/journals/10.1146/annurev-med-090518-093731&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    UNAIDS 2019. UNAIDS data 2019 Joint United Nations Programme on HIV/AIDS Geneva, Switz: https://www.unaids.org/en/resources/documents/2019/2019-UNAIDS-data. Accessed Sep. 10, 2019
  2. 2. 
    Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial Consortium 2019. HIV incidence among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a randomised, multicentre, open-label trial. Lancet 394:303–13
     [Google Scholar]
  3. 3. 
    Poteat T, Wirtz AL, Reisner S 2019. Strategies for engaging transgender populations in HIV prevention and care. Curr. Opin. HIV AIDS 14:393–400
     [Google Scholar]
  4. 4. 
    UNAIDS 2018. UNAIDS data 2018 Joint United Nations Programme on HIV/AIDS Geneva, Switz: https://www.unaids.org/en/resources/documents/2018/unaids-data-2018. Accessed Sep. 10, 2019
  5. 5. 
    Beyrer C, Baral SD, Collins C et al. 2016. The global response to HIV in men who have sex with men. Lancet 388:198–206
     [Google Scholar]
  6. 6. 
    Baeten JM, Donnell D, Ndase P et al. 2012. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 367:399–410
     [Google Scholar]
  7. 7. 
    Grant RM, Lama JR, Anderson PL et al. 2010. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N. Engl. J. Med. 363:2587–99
     [Google Scholar]
  8. 8. 
    FDA (US Food Drug Admin.) 2012. FDA approves first drug for reducing the risk of sexually acquired HIV infection Press release, July 16, US Food Drug Admin Washington, DC: https://aidsinfo.nih.gov/news/1254/fda-approves-first-drug-for-reducing-the-risk-of-sexually-acquired-hiv-infection
  9. 9. 
    Grulich AE, Guy R, Amin J et al. 2018. Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study. Lancet HIV 5:e629–e37
     [Google Scholar]
  10. 10. 
    Stein ZA. 1990. HIV prevention: the need for methods women can use. Am. J. Public Health 80:460–62
     [Google Scholar]
  11. 11. 
    Abdool Karim Q, Abdool Karim SS, Frohlich JA et al. 2010. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329:1168–74
     [Google Scholar]
  12. 12. 
    Marrazzo JM, Ramjee G, Richardson BA et al. 2015. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N. Engl. J. Med. 372:509–18
     [Google Scholar]
  13. 13. 
    Delany-Moretlwe S, Lombard C, Baron D et al. 2018. 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 18:1241–50
     [Google Scholar]
  14. 14. 
    Baeten JM, Palanee-Phillips T, Brown ER et al. 2016. Use of a vaginal ring containing dapivirine for HIV-1 prevention in women. N. Engl. J. Med. 375:2121–32
     [Google Scholar]
  15. 15. 
    Nel A, van Niekerk N, Kapiga S et al. 2016. Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women. N. Engl. J. Med. 375:2133–43
     [Google Scholar]
  16. 16. 
    Brown E, Palanee-Philips T, Marzinke M et al. 2016. Residual dapivirine ring levels indicate higher adherence to vaginal ring is associated with HIV-1 protection Presented at AIDS 2016: 21st International AIDS Conference, Durban, South Africa, Abstr. TUAC0105LB
  17. 17. 
    Riddler SA, Balkus JE, Parikh UM et al. 2019. Clinical and virologic outcomes following initiation of antiretroviral therapy among seroconverters in the Microbicide Trials Network-020 phase III trial of the dapivirine vaginal ring. Clin. Infect. Dis. 69:523–29
     [Google Scholar]
  18. 18. 
    Mugwanya KK, Wyatt C, Celum C et al. 2015. Changes in glomerular kidney function among HIV-1-uninfected men and women receiving emtricitabine-tenofovir disoproxil fumarate preexposure prophylaxis: a randomized clinical trial. JAMA Intern. Med. 175:246–54
     [Google Scholar]
  19. 19. 
    Baeten J, Palanee-Phillips T, Mgodi N et al. 2019. High adherence and sustained impact on HIV-1 incidence: final results of an open-label extension trial of the dapivirine vaginal ring Presented at IAS 2019: 10th IAS Conference on HIV Science Mexico City, Mexico: Abstr. TUAC0203
  20. 20. 
    Nel A, Malherbe M, Mans W et al. 2019. Safety, adherence and HIV-1 seroconversion in DREAM—an open-label dapivirine vaginal ring trial Abstract presented at 9th South Africa AIDS Conference Durban, South Africa:
  21. 21. 
    Grant RM, Anderson PL, McMahan V et al. 2014. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study. Lancet Infect. Dis. 14:820–29
     [Google Scholar]
  22. 22. 
    Thomson KA, Hughes J, Baeten JM et al. 2018. Increased risk of HIV acquisition among women throughout pregnancy and during the postpartum period: a prospective per-coital-act analysis among women with HIV-infected partners. J. Infect. Dis. 218:16–25
     [Google Scholar]
  23. 23. 
    Cranston RD, Lama JR, Richardson BA et al. 2017. MTN-017: a rectal phase 2 extended safety and acceptability study of tenofovir reduced-glycerin 1% gel. Clin. Infect. Dis. 64:614–20
     [Google Scholar]
  24. 24. 
    Carballo-Dieguez A, Balan IC, Brown W 3rd et al. 2017. High levels of adherence to a rectal microbicide gel and to oral preexposure prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women. PLOS ONE 12:e0181607
     [Google Scholar]
  25. 25. 
    Carballo-Dieguez A, Giguere R, Dolezal C et al. 2017. Preference of oral tenofovir disoproxil fumarate/emtricitabine versus rectal tenofovir reduced-glycerin 1% gel regimens for HIV prevention among cisgender men and transgender women who engage in receptive anal intercourse with men. AIDS Behav 21:3336–45
     [Google Scholar]
  26. 26. 
    Louissaint NA, Cao YJ, Skipper PL et al. 2013. Single dose pharmacokinetics of oral tenofovir in plasma, peripheral blood mononuclear cells, colonic tissue, and vaginal tissue. AIDS Res. Hum. Retroviruses 29:1443–50
     [Google Scholar]
  27. 27. 
    Cottrell ML, Yang KH, Prince HM et al. 2016. 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. 214:55–64
     [Google Scholar]
  28. 28. 
    Haaland RE, Holder A, Pau CP et al. 2017. Levels of intracellular phosphorylated tenofovir and emtricitabine correlate with natural substrate concentrations in peripheral blood mononuclear cells of persons prescribed daily oral truvada for HIV pre-exposure prophylaxis. J. Acquir. Immune Defic. Syndr. 75:e86–e88
     [Google Scholar]
  29. 29. 
    Madrasi K, Burns RN, Hendrix CW et al. 2014. Linking the population pharmacokinetics of tenofovir and its metabolites with its cellular uptake and metabolism. CPT Pharmacometrics Syst. Pharmacol. 3:e147
     [Google Scholar]
  30. 30. 
    Duwal S, von Kleist M 2016. Top-down and bottom-up modeling in system pharmacology to understand clinical efficacy: an example with NRTIs of HIV-1. Eur. J. Pharm. Sci. 94:72–83
     [Google Scholar]
  31. 31. 
    Louissaint NA, Nimmagadda S, Fuchs EJ et al. 2012. Distribution of cell-free and cell-associated HIV surrogates in the colon after simulated receptive anal intercourse in men who have sex with men. J. Acquir. Immune Defic. Syndr. 59:10–17
     [Google Scholar]
  32. 32. 
    Abner SR, Guenthner PC, Guarner J et al. 2005. A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infection. J. Infect. Dis. 192:1545–56
     [Google Scholar]
  33. 33. 
    Fletcher PS, Elliott J, Grivel JC et al. 2006. Ex vivo culture of human colorectal tissue for the evaluation of candidate microbicides. AIDS 20:1237–45
     [Google Scholar]
  34. 34. 
    Leyva F, Fuchs EJ, Bakshi R et al. 2015. Simultaneous evaluation of safety, acceptability, pericoital kinetics, and ex vivo pharmacodynamics comparing four rectal microbicide vehicle candidates. AIDS Res. Hum. Retroviruses 31:1089–97
     [Google Scholar]
  35. 35. 
    Leyva FJ, Bakshi RP, Fuchs EJ et al. 2013. Isoosmolar enemas demonstrate preferential gastrointestinal distribution, safety, and acceptability compared with hyperosmolar and hypoosmolar enemas as a potential delivery vehicle for rectal microbicides. AIDS Res. Hum. Retroviruses 29:1487–95
     [Google Scholar]
  36. 36. 
    Anton PA, Cranston RD, Kashuba A et al. 2012. RMP-02/MTN-006: a phase 1 rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of tenofovir 1% gel compared with oral tenofovir disoproxil fumarate. AIDS Res. Hum. Retroviruses 28:1412–21
     [Google Scholar]
  37. 37. 
    Cranston RD, Lama JR, Richardson BA et al. 2017. MTN-017: a rectal phase 2 extended safety and acceptability study of tenofovir reduced-glycerin 1% gel. Clin. Infect. Dis. 64:614–20
     [Google Scholar]
  38. 38. 
    Carballo-Dieguez A, Giguere R, Dolezal C et al. 2017. Preference of oral tenofovir disoproxil fumarate/emtricitabine versus rectal tenofovir reduced-glycerin 1% gel regimens for HIV prevention among cisgender men and transgender women who engage in receptive anal intercourse with men. AIDS Behav 21:3336–45
     [Google Scholar]
  39. 39. 
    Balan IC, Giguere R, Brown W 3rd et al. 2018. Brief participant-centered convergence interviews integrate self-reports, product returns, and pharmacokinetic results to improve adherence measurement in MTN-017. AIDS Behav 22:986–95
     [Google Scholar]
  40. 40. 
    Hiruy H, Fuchs EJ, Marzinke MA et al. 2015. A phase 1 randomized, blinded comparison of the pharmacokinetics and colonic distribution of three candidate rectal microbicide formulations of tenofovir 1% gel with simulated unprotected sex (CHARM-02). AIDS Res. Hum. Retroviruses 31:1098–108
     [Google Scholar]
  41. 41. 
    McGowan I, Cranston RD, Duffill K et al. 2015. A Phase 1 randomized, open label, rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of three formulations of tenofovir 1% gel (the CHARM-01 Study). PLOS ONE 10:e0125363
     [Google Scholar]
  42. 42. 
    McGowan I, Wilkin T, Landovitz RJ et al. 2019. The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM. AIDS 33:237–46
     [Google Scholar]
  43. 43. 
    Justman JE, Nair GL, Hendrix CW et al. 2018. Pharmacokinetics and pharmacodynamics of tenofovir reduced-glycerin 1% gel in the rectal and vaginal compartments in women: a cross-compartmental study with directly observed dosing. J. Acquir. Immune Defic. Syndr. 78:175–82
     [Google Scholar]
  44. 44. 
    Vincent KL, Moss JA, Marzinke MA et al. 2018. Phase I trial of pod-intravaginal rings delivering antiretroviral agents for HIV-1 prevention: rectal drug exposure from vaginal dosing with tenofovir disoproxil fumarate, emtricitabine, and maraviroc. PLOS ONE 13:e0201952
     [Google Scholar]
  45. 45. 
    Vincent KL, Moss JA, Marzinke MA et al. 2018. 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:e1002655
     [Google Scholar]
  46. 46. 
    Carballo-Dieguez A, Giguere R, Lentz C et al. 2019. Rectal douching practices associated with anal intercourse: implications for the development of a behaviorally congruent HIV-prevention rectal microbicide douche. AIDS Behav 23:1484–93
     [Google Scholar]
  47. 47. 
    Shieh EC, Weld ED, Fuchs EJ et al. 2017. Lubricant provides poor rectal mucosal HIV coverage. AIDS Res. Hum. Retroviruses 33:784–87
     [Google Scholar]
  48. 48. 
    Weld ED, Fuchs EJ, Marzinke MA et al. 2018. Tenofovir douche for PrEP: on demand, behaviorally-congruent douche rapidly achieves colon tissue concentration targets (DREAM 01 Study) Presented at HIV Research for Prevention (HIVR4P) Madrid, Spain: Abstr. OA20.03
  49. 49. 
    Molina JM, Capitant C, Spire B et al. 2015. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N. Engl. J. Med. 373:2237–46
     [Google Scholar]
  50. 50. 
    Xiao P, Gumber S, Marzinke MA et al. 2018. Hypo-osmolar rectal douche delivers tenofovir to the rectal mucosa and effectively protects macaques against repeated SHIV challenges Presented at HIV Research for Prevention (HIVR4P) Madrid, Spain: Abstr. P29.13LB
  51. 51. 
    Anderson PL, Glidden DV, Liu A et al. 2012. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci. Transl. Med. 4:151ra25
     [Google Scholar]
  52. 52. 
    Karim SS, Kashuba AD, Werner L, Karim QA 2011. Drug concentrations after topical and oral antiretroviral pre-exposure prophylaxis: implications for HIV prevention in women. Lancet 378:279–81
     [Google Scholar]
  53. 53. 
    Hendrix CW. 2013. Exploring concentration response in HIV pre-exposure prophylaxis to optimize clinical care and trial design. Cell 155:515–18
     [Google Scholar]
  54. 54. 
    Hendrix CW, Andrade A, Bumpus NN et al. 2016. Dose frequency ranging pharmacokinetic study of tenofovir-emtricitabine after directly observed dosing in healthy volunteers to establish adherence benchmarks (HPTN 066). AIDS Res. Hum. Retroviruses 32:32–43
     [Google Scholar]
  55. 55. 
    Anderson PL, Liu AY, Castillo-Mancilla JR et al. 2018. Intracellular tenofovir-diphosphate and emtricitabine-triphosphate in dried blood spots following directly observed therapy. Antimicrob. Agents Chemother. 62:01710–17
     [Google Scholar]
  56. 56. 
    Koss CA, Liu AY, Castillo-Mancilla J et al. 2018. Similar tenofovir hair concentrations in men and women after directly observed dosing of tenofovir disoproxil fumarate/emtricitabine: implications for preexposure prophylaxis adherence monitoring. AIDS 32:2189–94
     [Google Scholar]
  57. 57. 
    Drain PK, Kubiak RW, Siriprakaisil O et al. 2019. Urine tenofovir concentrations correlate with plasma and relates to TDF adherence: a randomized directly-observed pharmacokinetic trial (TARGET Study). Clin. Infect. Dis. 17: In press
    [Google Scholar]
  58. 58. 
    Balan IC, Giguere R, Brown W 3rd et al. 2018. Brief participant-centered convergence interviews integrate self-reports, product returns, and pharmacokinetic results to improve adherence measurement in MTN-017. AIDS Behav 22:986–95
     [Google Scholar]
  59. 59. 
    Husnik MJ, Brown ER, Marzinke M et al. 2017. Implementation of a novel adherence monitoring strategy in a phase III, blinded, placebo-controlled, HIV-1 prevention clinical trial. J. Acquir. Immune Defic. Syndr. 76:330–37
     [Google Scholar]
  60. 60. 
    Madrasi K, Burns RN, Hendrix CW et al. 2014. Linking the population pharmacokinetics of tenofovir and its metabolites with its cellular uptake and metabolism. CPT Pharmacometrics Syst. Pharmacol. 3:e147
     [Google Scholar]
  61. 61. 
    Hendrix CW, Chen BA, Guddera V et al. 2013. MTN-001: randomized pharmacokinetic cross-over study comparing tenofovir vaginal gel and oral tablets in vaginal tissue and other compartments. PLOS ONE 8:e55013
     [Google Scholar]
  62. 62. 
    McClelland RS, Lingappa JR, Srinivasan S et al. 2018. Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study. Lancet Infect. Dis. 18:554–64
     [Google Scholar]
  63. 63. 
    Srinivasan S, Richardson BA, Wallis J et al. 2018. Vaginal microbiota and HIV acquisition risk among African women Presented at CROI 2018: Conference on Retroviruses and Opportunistic Infections Boston, MA: Abstr 268
  64. 64. 
    Gosmann C, Anahtar MN, Handley SA et al. 2017. Lactobacillus-deficient cervicovaginal bacterial communities are associated with increased HIV acquisition in young South African women. Immunity 46:29–37
     [Google Scholar]
  65. 65. 
    Klatt NR, Cheu R, Birse K et al. 2017. Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women. Science 356:938–45
     [Google Scholar]
  66. 66. 
    Bunge KE, Dezzutti CS, Hendrix CW et al. 2018. FAME-04: a phase 1 trial to assess the safety, acceptability, pharmacokinetics and pharmacodynamics of film and gel formulations of tenofovir. J. Int. AIDS Soc. 21:e25156
     [Google Scholar]
  67. 67. 
    Hillier SL, Meyn LA, Bunge K et al. 2017. Impact of vaginal microbiota on genital tissue and plasma concentrations of tenofovir Presented at CROI 2017: Conference on Retroviruses and Opportunistic Infections Seattle, WA: Abstr. 86LB
  68. 68. 
    Taneva E, Sinclair S, Mesquita PM et al. 2018. Vaginal microbiome modulates topical antiretroviral drug pharmacokinetics. JCI Insight 3:99545
     [Google Scholar]
  69. 69. 
    Thurman AR, Schwartz JL, Ravel J et al. 2019. Vaginal microbiota and mucosal pharmacokinetics of tenofovir in healthy women using tenofovir and tenofovir/levonorgestrel vaginal rings. PLOS ONE 14:e0217229
     [Google Scholar]
  70. 70. 
    Heffron R, McClelland RS, Balkus JE et al. 2017. Efficacy of oral pre-exposure prophylaxis (PrEP) for HIV among women with abnormal vaginal microbiota: a post-hoc analysis of the randomised, placebo-controlled Partners PrEP Study. Lancet HIV 4:e449–e56
     [Google Scholar]
  71. 71. 
    Donahue Carlson R, Sheth AN, Read TD et al. 2017. The female genital tract microbiome is associated with vaginal antiretroviral drug concentrations in human immunodeficiency virus-infected women on antiretroviral therapy. J. Infect. Dis. 216:990–99
     [Google Scholar]
  72. 72. 
    Baeten JM, Brown ER, Hillier SL 2017. Dapivirine vaginal ring for HIV-1 prevention. N. Engl. J. Med. 376:995–96
     [Google Scholar]
  73. 73. 
    Nicol MR, Eneh P, Nakalega R et al. 2019. Depot medroxyprogesterone acetate and the vaginal microbiome as modifiers of tenofovir diphosphate and lamivudine triphosphate concentrations in the female genital tract of Ugandan women: implications for TDF/3TC in pre-exposure prophylaxis. Clin. Infect. Dis. 25: In press
    [Google Scholar]
  74. 74. 
    Nicol MR, Brewers LM, Kashuba ADM, Sykes C 2018. The role of menopause in tenofovir diphosphate and emtricitabine triphosphate concentrations in cervical tissue. AIDS 32:11–15
     [Google Scholar]
  75. 75. 
    Thurman AR, Schwartz JL, Brache V et al. 2019. Effect of hormonal contraception on pharmacokinetics of vaginal tenofovir in healthy women: increased tenofovir diphosphate in injectable depot medroxyprogesterone acetate users. J. Acquir. Immune Defic. Syndr. 80:79–88
     [Google Scholar]
  76. 76. 
    van der Straten A, Stadler J, Montgomery E et al. 2014. Women's experiences with oral and vaginal pre-exposure prophylaxis: the VOICE-C qualitative study in Johannesburg, South Africa. PLOS ONE 9:e89118
     [Google Scholar]
  77. 77. 
    Montgomery ET, Beksinska M, Mgodi N et al. 2019. End-user preference for and choice of four vaginally delivered HIV prevention methods among young women in South Africa and Zimbabwe: the Quatro Clinical Crossover Study. J. Int. AIDS Soc. 22:e25283
     [Google Scholar]
  78. 78. 
    Montgomery ET, Stadler J, Naidoo S et al. 2018. Reasons for nonadherence to the dapivirine vaginal ring: narrative explanations of objective drug-level results. AIDS 32:1517–25
     [Google Scholar]
  79. 79. 
    Palanee-Phillips T, Roberts ST, Reddy K et al. 2018. Impact of partner-related social harms on women's adherence to the dapivirine vaginal ring during a phase III trial. J. Acquir. Immune Defic. Syndr. 79:580–89
     [Google Scholar]
  80. 80. 
    Jain AK. 1989. Fertility reduction and the quality of family planning services. Stud. Fam. Plann. 20:1–16
     [Google Scholar]
  81. 81. 
    Secura GM, Madden T, McNicholas C et al. 2014. Provision of no-cost, long-acting contraception and teenage pregnancy. N. Engl. J. Med. 371:1316–23
     [Google Scholar]
  82. 82. 
    Young Holt B, Dellplain L, Creinin MD et al. 2018. A strategic action framework for multipurpose prevention technologies combining contraceptive hormones and antiretroviral drugs to prevent pregnancy and HIV. Eur. J. Contracept. Reprod. Health Care 23:326–34
     [Google Scholar]
  83. 83. 
    Thurman AR, Schwartz JL, Brache V et al. 2018. Randomized, placebo controlled phase I trial of safety, pharmacokinetics, pharmacodynamics and acceptability of tenofovir and tenofovir plus levonorgestrel vaginal rings in women. PLOS ONE 13:e0199778
     [Google Scholar]
  84. 84. 
    Dallal Bashi YH, McCoy CF, Murphy DJ et al. 2019. Towards a dapivirine and levonorgestrel multipurpose vaginal ring: investigations into the reaction between levonorgestrel and addition-cure silicone elastomers. Int. J. Pharm. 569:118574
     [Google Scholar]
  85. 85. 
    Bunge K, Levy L, Szydlo D et al. 2017. Safety and acceptability trial of the dapivirine vaginal ring in U.S. adolescents Presented at IAS 2017: 9th IAS Conference on HIV Science Paris, France: Abstr. TUAC0206LB
  86. 86. 
    Chen BA, Zhang J, Gundacker HM et al. 2019. Phase 2a safety, pharmacokinetics, and acceptability of dapivirine vaginal rings in US postmenopausal women. Clin. Infect. Dis. 68:1144–51
     [Google Scholar]
  87. 87. 
    Makanani B, Balkus JE, Jiao Y et al. 2018. Pregnancy and infant outcomes among women using the dapivirine vaginal ring in early pregnancy. J. Acquir. Immune Defic. Syndr. 79:566–72
     [Google Scholar]
  88. 88. 
    Balkus JE, Palanee-Phillips T, Reddy K et al. 2017. Dapivirine vaginal ring use does not diminish the effectiveness of hormonal contraception. J. Acquir. Immune Defic. Syndr. 76:e47–e51
     [Google Scholar]
  89. 89. 
    Noguchi LM, Hoesley C, Kelly C et al. 2019. Pharmacokinetics of dapivirine transfer into blood plasma, breast milk, and cervicovaginal fluid of lactating women using the dapivirine vaginal ring. Antimicrob. Agents Chemother. 63:01930–18
     [Google Scholar]
/content/journals/10.1146/annurev-med-090518-093731
Loading
Topical Microbicides in HIV Prevention: State of the Promise
Annual Review of Medicine 71, 361 (2020); https://doi.org/10.1146/annurev-med-090518-093731
/content/journals/10.1146/annurev-med-090518-093731
/content/journals/10.1146/annurev-med-090518-093731
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error