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Promising Prevention Approaches: Tenofovir Gel and Prophylactic Use of Antiretroviral Medications

  • Behavioral Aspects of HIV Management (Ralph J. DiClemente and Jennifer Brown, Section Editors)
  • Published:
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Abstract

Thirty years into the global HIV epidemic, the need for effective prevention strategies remains critical. In July 2010, the CAPRISA-004 study demonstrated that topical administration of a gel containing the antiretroviral agent tenofovir decreased the risk of HIV acquisition among at-risk heterosexual women. Subsequently, the iPrEx study reported that prophylactic use of a daily oral tablet containing tenofovir and emtricitabine reduced the risk of HIV acquisition among high-risk men who have sex with men. These studies illustrate the promise of antiretroviral pre-exposure chemoprophylaxis (PrEP) as an innovative prevention approach. This review discusses the rationale for chemoprophylaxis, compares the advantages of topical and oral delivery, outlines recommended safety monitoring, offers principles to guide selection of antiretroviral agents, and highlights potential unintended consequences of PrEP use. If future studies confirm the safety and efficacy of tenofovir gel and oral PrEP, successful implementation of these strategies could significantly impact the HIV epidemic.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. UNAIDS: Report on the Global AIDS Epidemic. Available at http://www.unaids.org/GlobalReport/default.htm. Accessed June 2011.

  2. Dieffenbach CW, Fauci AS. Thirty years of HIV and AIDS: future challenges and opportunities. Ann Intern Med. 2011;154(11):766–71.

    PubMed  Google Scholar 

  3. •• 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;329(5996):1168–74. This reference reports the results of CAPRISA-004, a community-based, randomized controlled trial that demonstrated the efficacy of topical tenofovir gel in reducing the risk of HIV acquisition by 39% among at-risk heterosexual women in South Africa.

    Article  PubMed  CAS  Google Scholar 

  4. •• Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):2587–99. This reference reports the results of iPrEx, a multinational, randomized controlled trial in which daily administration of oral FTC-TDF decreased the risk of HIV acquisition among high-risk MSM and transgender women by 44%.

    Article  PubMed  CAS  Google Scholar 

  5. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. N Engl J Med. 1997;337(21):1485–90.

    Article  PubMed  CAS  Google Scholar 

  6. Schechter M, do Lago RF, Mendelsohn AB, et al. Behavioral impact, acceptability, and HIV incidence among homosexual men with access to postexposure chemoprophylaxis for HIV. J Acquir Immune Defic Syndr. 2004;35(5):519–25.

    Article  PubMed  Google Scholar 

  7. Garcia-Lerma JG, Cong ME, Mitchell J, et al. Intermittent prophylaxis with oral truvada protects macaques from rectal SHIV infection. Sci Transl Med. 2010;2(14):14ra14.

    Article  Google Scholar 

  8. Peterson L, Taylor D, Roddy R, et al. Tenofovir disoproxil fumarate for prevention of HIV infection in women: a phase 2, double-blind, randomized, placebo-controlled trial. PLoS Clin Trials. 2007;2(5):e27.

    Article  PubMed  Google Scholar 

  9. Mayer KH, Maslankowski LA, Gai F, et al. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006;20(4):543–51.

    Article  PubMed  CAS  Google Scholar 

  10. Hendrix C, Minnis A, Guddera V, et al. MTN-001: a phase 2 cross-over study of daily oral and vaginal TFV in healthy, sexually active women results in significantly different product acceptability and vaginal tissue drug concentrations. [abstract 35LB]. Presented at the 18th Conference on Retroviruses and Opportunistic Infections. Boston; February 27-March 2, 2011.

  11. Hillier S. Safety and acceptability of coitally dependant use of 1% tenofovir over six months of use. [abstract BO12-655]. Presented at the Microbicides 2008 Conference. New Delhi, India; February 24–27, 2008.

  12. AIDS Vaccine Advocacy Coalition (AVAC): Global Advocacy for HIV Prevention website. Available at http://www.avac.org. Accessed June 2011.

  13. CONRAD: Press Release: FDA and CONRAD Chart U.S. Regulatory Path for 1% Tenofovir Gel for HIV Prevention. Available at http://www.conrad.org/news-pressreleases-56.html. Accessed June 2010.

  14. Anton P, Cranston R, Carballo-Dieguez A, et al. RMP-02/MTN-006: a phase 1 placebo-controlled trial of rectally applied 1% vaginal TFV gel with comparison to oral TDF. [abstract 34LB]. Presented at the 18th Conference on Retroviruses and Opportunistic Infections. Boston; February 27–March 2, 2011.

  15. Baeten J, Celum C. Antiretroviral pre-exposure prophylaxis for HIV-1 prevention among heterosexual African men and women: the partners PrEP study [abstract MOAX0106]. Presented at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Rome, Italy; July 17–20, 2011.

  16. Thigpen MC, Kebaabetswe PM, Smith DK, et al. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 Study. [abstract WELBC01]. Presented at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Rome, Italy; July 17–20, 2011.

  17. Family Health International: FHI to Initiate Orderly Closure of FEM-PrEP. Available at http://www.fhi.org/en/Research/Projects/FEM-PrEP.htm. Accessed June 2011.

  18. Zimmermann AE, Pizzoferrato T, Bedford J, et al. Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions. Clin Infect Dis. 2006;42(2):283–90.

    Article  PubMed  CAS  Google Scholar 

  19. Szczech LA. Renal dysfunction and tenofovir toxicity in HIV-infected patients. Top HIV Med. 2008;16(4):122–6.

    PubMed  Google Scholar 

  20. Labarga P, Barreiro P, Martin-Carbonero L, et al. Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir. AIDS. 2009;23(6):689–96.

    Article  PubMed  CAS  Google Scholar 

  21. Cooper Ryan D, Wiebe N, Smith N, et al. Systematic review and meta–analysis: renal safety of tenofovir disoproxil fumarate in HIV–infected patients. Clin Infect Dis. 2010;51(5):496–505.

    Article  PubMed  CAS  Google Scholar 

  22. Jacobson DL, Spiegelman D, Knox TK, Wilson IB. Evolution and predictors of change in total bone mineral density over time in HIV-infected men and women in the nutrition for healthy living study. J Acquir Immune Defic Syndr. 2008;49(3):298–308.

    Article  PubMed  CAS  Google Scholar 

  23. Liu A, Vittinghoff E, Irby R, et al. BMD loss in HIV—men participating in a TDF PrEP clinical trial in San Francisco. [abstract 93]. Presented at the 18th Conference on Retroviruses and Opportunistic Infections. Boston; February 27-March 2, 2011.

  24. • Interim Guidance: preexposure prophylaxis for the prevention of HIV infection in men who have sex with men. MMWR Morb Mortal Wkly Rep. 2011;60(3):65–8. This reference is a summary of interim guidance from the CDC on the use of daily oral chemoprophylaxis with FTC-TDF in high-risk MSM. The authors outline current recommendations around laboratory and clinical monitoring associated with PrEP use in this population.

  25. Liegler T, Abdel-Mohsen M, Atchison R, et al. Drug resistance and minor drug resistant variants in iPrEx. [abstract 97LB]. Presented at the 18th Conference on Retroviruses and Opportunistic Infections. Boston; February 27–March 2, 2011.

  26. Kwara A, DeLong A, Rezk N, et al. Antiretroviral drug concentrations and HIV RNA in the genital tract of HIV–infected women receiving long–term highly active antiretroviral therapy. Clin Infect Dis. 2008;46(5):719–25.

    Article  PubMed  CAS  Google Scholar 

  27. HIV Prevention Trials Network: HPTN Studies. Available at http://www.hptn.org/research_studies.asp. Accessed June 2011.

  28. Dumond JB, Yeh RF, Patterson KB, et al. Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis. AIDS. 2007;21(14):1899–907.

    Article  PubMed  CAS  Google Scholar 

  29. Van Rompay KK, Matthews TB, Higgins J, et al. Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase. J Virol. 2002;76(12):6083–92.

    Article  PubMed  Google Scholar 

  30. Dumond JB, Patterson KB, Pecha AL, et al. Maraviroc concentrates in the cervicovaginal fluid and vaginal tissue of HIV-negative women. J Acquir Immune Defic Syndr. 2009;51(5):546–53.

    Article  PubMed  Google Scholar 

  31. Nel A, Smythe S, Young K, Malcolm K, et al. Safety and pharmacokinetics of dapivirine delivery from matrix and reservoir intravaginal rings to HIV-negative women. J Acquir Immune Defic Syndr. 2009;51(4):416–23.

    Article  PubMed  CAS  Google Scholar 

  32. Patton DL, Sweeney YT, Balkus JE, et al. Preclinical safety assessments of UC781 anti-human immunodeficiency virus topical microbicide formulations. Antimicrob Agents Chemother. 2007;51(5):1608–15.

    Article  PubMed  CAS  Google Scholar 

  33. Ghosn J, Chaix ML, Peytavin G, et al. Penetration of enfuvirtide, tenofovir, efavirenz, and protease inhibitors in the genital tract of HIV-1-infected men. AIDS. 2004;18(14):1958–61.

    Article  PubMed  Google Scholar 

  34. Patel SM, Johnson S, Belknap SM, et al. Serious adverse cutaneous and hepatic toxicities associated with nevirapine use by non-HIV-infected individuals. J Acquir Immune Defic Syndr. 2004;35(2):120–5.

    Article  PubMed  CAS  Google Scholar 

  35. Mallal S, Nolan D, Witt C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002;359(9308):727–32.

    Article  PubMed  CAS  Google Scholar 

  36. Amico KR, Liu A, McMahan V, et al. Adherence indicators and PrEP drug levels in the iPrEx study. [abstract 95LB]. Presented at the 18th Conference on Retroviruses and Opportunistic Infections. Boston; February 27–March 2, 2011.

  37. Stirratt MJ, Gordon CM. Adherence to biomedical HIV prevention methods: considerations drawn from HIV treatment adherence research. Curr HIV/AIDS Rep. 2008;5(4):186–92.

    Article  PubMed  Google Scholar 

  38. Guest G, Shattuck D, Johnson L, et al. Changes in sexual risk behavior among participants in a PrEP HIV prevention trial. Sex Transm Dis. 2008;35(12):1002–8.

    PubMed  Google Scholar 

  39. Golub SA, Kowalczyk W, Weinberger CL, Parsons JT. Preexposure prophylaxis and predicted condom use among high-risk men who have sex with men. J Acquir Immune Defic Syndr. 2010;54(5):548–55.

    Article  PubMed  Google Scholar 

  40. Mayer KH, Krakower D, Novak DS, et al. On-line assessment of Pre-Exposure Prophylaxis (PrEP) knowledge, attitudes and experience among at risk American Men who have Sex with Men (MSM) before and after the publication of the iPrEx trial results. [abstract TUPE360]. Accepted to the 6th IAS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Rome, Italy; July 17–20, 2011.

  41. Mugavero MJ, Norton WE, Saag MS. Health care system and policy factors influencing engagement in HIV medical care: piecing together the fragments of a fractured health care delivery system. Clin Infect Dis. 2010;52(Supplement 2):S238–46.

    Article  Google Scholar 

  42. Yarnall KS, Pollak KI, Ostbye T, Krause KM, Michener JL. Primary care: is there enough time for prevention? Am J Public Health. 2003;93(4):635–41.

    Article  PubMed  Google Scholar 

  43. Desai K, Sansom SL, Ackers ML, et al. Modeling the impact of HIV chemoprophylaxis strategies among men who have sex with men in the United States: HIV infections prevented and cost-effectiveness. AIDS. 2008;22(14):1829–39.

    Article  PubMed  Google Scholar 

  44. Paltiel AD, Freedberg KA, Scott CA, et al. HIV preexposure prophylaxis in the United States: impact on lifetime infection risk, clinical outcomes, and cost-effectiveness. Clin Infect Dis. 2009;48(6):806–15.

    Article  PubMed  Google Scholar 

  45. Walensky R, Park J-E, Wood R, Freedberg K, Scott C, Bekker LG, et al. Cost effectiveness of PrEP for HIV infection in South Africa. [abstract 37LB]. Presented at the 18th Conference on Retroviruses and Opportunistic Infections. Boston; February 27–March 2, 2011.

  46. The Wall Street Journal: New Gel Cuts Risk of HIV Infection. Available at http://online.wsj.com/article/SB10001424052748704720004575377140651050822.html. Accessed August 2011.

  47. Montano DE, Phillips WR, Kasprzyk D, Greek A. STD/HIV prevention practices among primary care clinicians: risk assessment, prevention counseling, and testing. Sex Transm Dis. 2008;35(2):154–66.

    Article  PubMed  Google Scholar 

  48. Epstein RM, Morse DS, Frankel RM, et al. Awkward moments in patient-physician communication about HIV risk. Ann Intern Med. 1998;128(6):435–42.

    PubMed  CAS  Google Scholar 

  49. Peterman TA, Lin LS, Newman DR, et al. Does measured behavior reflect STD risk? An analysis of data from a randomized controlled behavioral intervention study. Project RESPECT Study Group. Sex Transm Dis. 2000;27(8):446–51.

    Article  PubMed  CAS  Google Scholar 

  50. Buchbinder SP, Liu A. Pre-exposure prophylaxis and the promise of combination prevention approaches. AIDS Behav. 2011;15 Suppl 1:S72–9.

    Article  PubMed  Google Scholar 

  51. Siegfried N, Muller M, Deeks JJ, Volmink J. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev. 2009(2):CD003362.

  52. Chigwedere P, Seage GR, Lee T-H, Essex M. Efficacy of antiretroviral drugs in reducing mother-to-child transmission of HIV in Africa: a meta-analysis of published clinical trials. AIDS Res Hum Retrovir. 2008;24(6):827–37.

    Article  PubMed  CAS  Google Scholar 

  53. Cohen Myron S, Gay Cynthia L. Treatment to prevent transmission of HIV–1. Clin Inf Dis. 2010;50(3):S85–95.

    Article  Google Scholar 

  54. Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet. 2010;375(9731):2092–8.

    Article  PubMed  Google Scholar 

  55. HIV Prevention Trials Network: Press Release: initiation of antiretroviral treatment protects uninfected sexual partners from HIV infection (HPTN Study 052). Available at http://www.hptn.org/web%20documents/PressReleases/HPTN052PressReleaseFINAL5_12_118am.pdf. Accessed June 2011.

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, W/LMOB Suite GB, Boston, MA, 02215, USA

    Douglas Krakower

  2. The Fenway Institute, Fenway Health, and Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA

    Kenneth H. Mayer

  3. The Fenway Institute, Fenway Health, 1340 Boylston Street, Boston, MA, 02215, USA

    Kenneth H. Mayer

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  1. Douglas Krakower
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Correspondence to Kenneth H. Mayer.

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Krakower, D., Mayer, K.H. Promising Prevention Approaches: Tenofovir Gel and Prophylactic Use of Antiretroviral Medications. Curr HIV/AIDS Rep 8, 241–248 (2011). https://doi.org/10.1007/s11904-011-0094-4

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