It’s Time: The Case for PrEP as an Active Comparator in HIV Biomedical Prevention Trials

Abdool Karim, Q., S.S. Abdool Karim, J.A. Frohlich, et al. 2010. Effectiveness and safety of Tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329(5996): 1168–1174.

Anderson, P.L., D.V. Glidden, A. Liu, et al. 2012. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Science Translational Medicine 4(151): 151ra125.

Angell, M. 1997. The ethics of clinical research in the third world. The New England Journal of Medicine 337(12): 847–849.

Auvert, B., D. Taljaard, E. Lagarde, J. Sobngwi-Tambekou, R. Sitta, and A. Puren. 2005. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 trial. PLoS Med 2(11): e298. doi:10.1371/journal.pmed.0020298.

Baeten, J.M., D. Donnell, P. Ndase, et al. 2012. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. The New England Journal of Medicine 367(5): 399–410.

Bailey, R.C., S. Moses, C.B. Parker, et al. 2007. Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomised controlled trial. The Lancet 369(9562): 643–656.

Belsky, L., and H.S. Richardson. 2004. Medical researchers’ ancillary clinical care responsibilities. British Medical Journal 328(7454): 1494–1496.

Choopanya, K., M. Martin, P. Suntharasamai, et al. 2013. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): A randomised, double-blind, placebo-controlled phase 3 trial. The Lancet 381(9883): 2083–2090.

Cohen, M.S., Y.Q. Chen, M. McCauley, et al. 2011. Prevention of HIV-1 infection with early antiretroviral therapy. The New England Journal of Medicine 365(6): 493–505.

Council for International Organizations of Medical Sciences [CIOMS]. 2002. International ethical guidelines for biomedical research involving human subjects. Geneva: CIOMS and WHO. http://www.cioms.ch/images/stories/CIOMS/guidelines/guidelines_nov_2002_blurb.htm . Accessed July 30, 2013.

Fleming, T. 2013. Non-inferiority clinical trials: Some key consideration in PrEP and microbicide studies. Presentation at the meeting on the Future of PrEP and Microbicide Research: Trial Design and Regulatory Issues, January 7, in Washington, DC. http://www.hivforum.org/storage/hivforum/documents/FutureofPrEP/session_2_fleming.pdf . Accessed February 1, 2013.

Follow-on African Consortium for Tenofovir Studies [FACTS]. No date. FACTS 001 study. http://www.facts-consortium.co.za/?page_id=83 . Accessed July 30, 2013.

Food and Drug Administration [FDA]. 2012. FDA approves first drug for reducing the risk of sexually acquired HIV infection: Evidence-based approach enhances existing prevention strategies. U.S. Food and Drug Administration, July 16. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312210.htm . Accessed September 10, 2012.

Forbes, A., and S. Mudaliar. 2009. Preventing prevention trial failures: A case study and lessons learned for future trials from the 2004 tenofovir trial in Cambodia. Washington, DC: Global Campaign for Microbicides. http://www.global-campaign.org/clientfiles/Cambodia.pdf .

Grant, R.M., J.R. Lama, P.L. Anderson, et al. 2010. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. The New England Journal of Medicine 363(27): 2587–2599.

Gray, R.H., G. Kigozi, D. Serwadda, et al. 2007. Male circumcision for HIV prevention in men in Rakai, Uganda: A randomised trial. The Lancet 369(9562): 657–666.

Haire, B.G. 2011. Because we can: Clashes of perspective over researcher obligation in the failed PrEP trials. Developing World Bioethics 11(2): 63–74.

Haire, B., J. Kaldor, and C.F.C. Jordens. 2012. How good is “good enough”? The case for varying standards of evidence according to need for new interventions in HIV prevention. The American Journal of Bioethics 12(6): 21–30.

HIV Prevention Trials Network [HPTN]. No date. HPTN 071: The PopART study. http://www.hptn.org/web%20documents/IndexDocs/071StudyAnnouncement14Sep11.pdf . Accessed December 18, 201.

Holt M., Murphy D.A., Callander D., et al. 2011. Willingness to use HIV pre-exposure prophylaxis and the likelihood of decreased condom use are both associated with unprotected anal intercourse and the perceived likelihood of becoming HIV positive among Australian gay and bisexual men. Sexually Transmitted Infections 88(4): 258–263.

IRIN Humanitarian News and Analysis. 2013. Thousands still missing HIV treatment following CAR coup. IRIN Humanitarian News and Analysis, June 11. http://www.irinnews.org/report/98208/thousands-still-missing-hiv-treatment-following-car-coup . Accessed July 30, 2013.

Knox, R., and M. Doucleff. 2012. Clinton reveals blueprint for an “AIDS-free generation.” Shots: Health News From National Public Radio, November 29. http://www.npr.org/blogs/health/2012/11/29/166154269/clinton-reveals-blueprint-for-an-aids-free-generation .

Krebs, J. 2008. The importance of public health ethics. Bulletin of the World Health Organization 86(8): 577–656. http://www.who.int/bulletin/volumes/86/8/08-052431/en/ .

Lurie, P., and S. M. Wolfe. 1997. Unethical trials of interventions to reduce perinatal transmission of the human immunodeficiency virus in developing countries. The New England Journal of Medicine 337(12): 853–856.

Macklin, R. 2001. After Helsinki: Unresolved issues in international research. Kennedy Institute of Ethics Journal 11(1): 17–36.

Macklin, R. 2006. Changing the presumption: Providing ART to vaccine research participants. The American Journal of Bioethics 6(1): 1–5.

Macklin, R. 2008. Standard of care: An evolution in ethical thinking. The Lancet 372(9635): 284–285.

May, M., M. Gompels, and C. Sabin. 2012. Life expectancy of HIV-1-positive individuals approaches normal, conditional on response to antiretroviral therapy: UK collaborative HIV cohort study. Abstract from the Eleventh International Congress on Drug Therapy in HIV Infection, November 11–15, in Glasgow, Scotland.

Mayer, K. 2013. Future of PrEP and microbicide research: Setting the stage. Presentation at the meeting on the Future of PrEP and Microbicide Research: Trial Design and Regulatory Issues, January 7, in Washington, DC. http://www.hivforum.org/storage/hivforum/documents/FutureofPrEP/session_1_mayer.pdf . Accessed February 2, 2013.

McGrory, E., A. Irvin, and L. Heise. 2009. Research Rashomon: Lessons from the Cameroon pre-exposure prophylaxis trial site. Washington, DC: Global Campaign for Microbicides. www.globalcampaign.org/clientfiles/Cameroon.pdf. Accessed January 8, 2011.

Microbicide Trials Network [MTN]. 2013. Understanding the results of VOICE. http://www.mtnstopshiv.org/news/studies/mtn003 . Accessed March 12, 2013.

Miller, P.B., and C. Weijer. 2006. Fiduciary obligation in clinical research. The Journal of Law, Medicine and Ethics 34(2): 424–440.

PopART. 2013 About PopART. http://www1.imperial.ac.uk/departmentofmedicine/divisions/infectiousdiseases/infectious_diseases/hiv_trials/hiv_prevention_technologies/popart/about/ . Accessed July 30, 2013.

Rennie, S., and J. Sugarman. 2010. Developing ethics guidance for HIV prevention research: The HIV Prevention Trials Network approach. Journal of Medical Ethics 36(12): 810–815.

Rennie S., J. Sugarman, and the HPTN Ethics Working Group. 2009. HIV Prevention Trials Network ethics guidance for research. http://www.hptn.org/web%20documents/EWG/HPTNEthicsGuidanceV10Jun2009.pdf . Accessed July 31, 2012.

Rerks-Ngarm, S., P. Pitisuttithum, S. Nitayaphan, et al. 2009. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. The New England Journal of Medicine 361(23): 2209–2220.

Richardson, H.S. 2007. Gradations of researchers’ obligation to provide ancillary care for HIV/AIDS in developing countries. American Journal of Public Health 97(11): 1956–1961.

Thigpen, M.C., P.M. Kebaabetswe, L.A. Paxton, et al. 2012. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. The New England Journal of Medicine 367(5): 423–434.

Ukpong, M., and K. Peterson, eds. 2009. Oral tenofovir controversy II: Voices from the field. Falomo, Nigeria: New HIV Vaccines and Microbicides Society (NHVMAS)

UNAIDS. 2011. Good participatory practice: Guidelines for biomedical HIV prevention trials 2011, 2nd ed. Geneva: Joint United Nations Programme on HIV/AIDS [UNAIDS]. http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2011/JC1853_GPP_Guidelines_2011_en.pdf . Accessed February 2, 2013.

UNAIDS. 2012. UNAIDS report on the global AIDS epidemic 2012. Geneva: Joint United Nations Programme on HIV/AIDS [UNAIDS]. http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/20121120_UNAIDS_Global_Report_2012_with_annexes_en.pdf . Accessed January 30, 2013.

UNAIDS/WHO. 2012. Ethical considerations in biomedical HIV prevention trials. UNAIDS/WHO guidance document. Geneva: Joint United Nations Programme on HIV⁄AIDS [UNAIDS] and the World Health Organization [WHO]. http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2012/jc1399_ethical_considerations_en.pdf . Accessed January 14, 2013.

Vallely, A., C. Shagi, S. Kasindi, et al. 2007. The benefits of participatory methodologies to develop effective community dialogue in the context of a microbicide trial feasibility study in Mwanza, Tanzania. BMC Public Health 7: 133.

Van Damme, L., A. Corneli, K. Ahmed, et al. 2012. Preexposure prophylaxis for HIV infection among African women. The New England Journal of Medicine 367(5): 411–422.

van der Graaf, R., and J.J.M. van Delden. 2009. What is the best standard for the standard of care in clinical research? The American Journal of Bioethics 9(3): 35–43.

Varmus, H., and D. Satcher. 1997. Ethical complexities of conducting research in developing countries. The New England Journal of Medicine 337(14): 1003–1005.

Wheelock, A., A.B.. Eisingerich, J. Ananworanich, et al. 2013. Are Thai MSM willing to take PrEP for HIV prevention? An analysis of attitudes, preferences and acceptance. PLoS ONE 8(1): e54288. doi:10.1371/journal.pone.0054288.

World Health Organization [WHO]. 2013. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: Recommendations for a public health approach. Geneva: WHO. http://www.who.int/hiv/pub/guidelines/arv2013/download/en/index.html . Accessed July 30, 2013.

World Medical Association [WMA]. 1948. WMA Declaration of Geneva. http://www.wma.net/en/30publications/10policies/g1/. Accessed February 6, 2013

World Medical Association [WMA]. 2013. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. http://www.wma.net/en/30publications/10policies/b3/17c.pdf . Accessed February 6, 2013.