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Footnotes

  • 1
    B. Auvert et al. Randomized, Controlled Intervention Trial of Male Circumcision for Reduction of HIV Infection Risk: The ANRS 1265 Trial. PLoS Med 2005; 2: e298; R. Bailey et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 2007; 369: 643656; R. Gray et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 2007; 369: 657666.
  • 2
    S.S. Abdool Karim & Q. Abdool Karim. Antiretroviral Prophylaxis: a Defining Moment in HIV control. Lancet 2011; 378: e23e25.
  • 3
    Q. Abdool Karim et al. Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women. Science 2010; 329: 11681174; R.M. Grant et al. Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men. N Engl J Med 2010; 363: 25872599; M.S. Cohen et al. Prevention of HIV-1 Infection with Early Antiretroviral Therapy. N Engl J Med 2011; 365: 493505; J.M. Baeten et al. Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women. N Engl J Med 2012; 367: 399410; M.C. Thigpen et al. Antiretroviral Preexposure Prophylaxis for Heterosexual HIV Transmission in Botswana. N Engl J Med 2012; 367: 423434.
  • 4
    Grant et al. op. cit. note 3; Cohen et al. op. cit. note 3; Baeten et al. op. cit. note 3; Thigpen et al. op. cit. note 3.
  • 5
    Similar issues have been canvassed in Zaynab, Slack & Koen et al. HIV prevention responsibilities in HIV vaccine trials: Complexities facing South African researchers. South African Medical Journal 2010; 100: 4548.
  • 6
    Food and Drug Administration. (FDA). 2012. FDA Approves First Drug for Reducing the Risk of Sexually Acquired HIV Infection. (News release) July 16 2012. Silver Spring, MD: FDA. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312210.htm [Accessed 18 Feb 2013].
  • 7
    Centers for Disease Control. (CDC). 2012. CDC Issues Interim Guidance on Use of Medication to Prevent HIV Infection among Heterosexually Active Adults. (News release) August 9 2012. Atlanta, GA: CDC. Available at: http://www.cdc.gov/nchhstp/newsroom/2012/PrEP-HeterosexualGuidance-PressRelease.html [Accessed 18 Feb 2013].
  • 8
    This term was coined in 2007 in the UNAIDS Ethical Considerations document in hopes of minimizing confusion caused the multiple meanings of ‘standard of care’.
  • 9
    H.S. Richardson. Gradations of Researchers' Obligation to Provide Ancillary Care for HIV/AIDS in Developing Countries. Am J Public Health 2007; 97: 19561961; L. Belsky & H.S. Richardson. Medical researchers' ancillary clinical care responsibilities. BMJ 2004; 328: 14941496.
  • 10
    R. van der Graaf & J.J.M. van Delden. What is the Best Standard for the Standard of Care in Clinical Research? The American Journal of Bioethics 2009; 9: 3543.
  • 11
    L. Heise, K. Shapiro & K. West Slevin. Mapping the Standards of Care at Microbicide Clinical Trial Sites. Washington, DC: Global Campaign for Microbicides; 2008; B. Haire. 2013. Principal Investigator Questionnaire on HIV Prevention Trial Standards 2009–2012. (Unpublished) Sydney: University of Sydney.
  • 12
    Abdool Karim et al. op. cit. note 3; Grant et al. op. cit. note 3; Cohen et al. op. cit. note 3; Baeten et al. op. cit. note 3; Thigpen et al. op. cit. note 3.
  • 13
    Joint United Nations Programme on HIV/AIDS (UNAIDS), World Health Organization (WHO). 2012 (English original 2007, additional guidance point added 2012). UNAIDS/07.28E/JC1349E Ethical Considerations in Biomedical HIV Prevention Trials. UNAIDS/WHO Guidance Document. Geneva: UNAIDS and World Health Organization. Available at: http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2012/jc1399_ethical_considerations_en.pdf [Accessed 18 Feb 2013].
  • 14
    S. Rennie, J. Sugarman and the HPTN Ethics Working Group. 2009. HIV Prevention Trials Network Ethics Guidance for Research. HIV Prevention Trials Network. Available at: http://www.hptn.org/web%20documents/EWG/HPTNEthicsGuidanceV10Jun2009.pdf [Accessed 18 Feb 2013].
  • 15
    In addition, African countries including South Africa, Kenya and Uganda have developed their own guidelines for HIV prevention research. Thanks to an anonymous reviewer for highlighting these points.
  • 16
    Disclosure: one of the authors of this article coordinated the 2007 and 2011 revisions of the UNAIDS/WHO guidance while two authors were members of the oversight committee producing the 2007 UNAIDS/WHO Guidelines. One of the authors was a primary author of the HPTN Guidelines.
  • 17
    S. Rennie, J. Sugarman and the HPTN Ethics Group, op. cit. note 9, p. 14.
  • 18
    When conducting a study, a principal investigator can address within-country disparities through cooperation and referral networks with local health services, but international disparities may be impossible to address due to major funding and infrastructure deficits.
  • 19
    S. Rennie & J. Sugarman. Developing Ethics Guidance for HIV Prevention Research: the HIV Prevention Trials Network Approach. J Med Ethics 2010; 36: 810815.
  • 20
    Ibid.
  • 21
    S. Rennie, J. Sugarman and the HPTN Ethics Group. op. cit. note 9.
  • 22
    For a critique of scientific validation, see B. Haire, J. Kaldor & C.F.C. Jordens. 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 2012; 12: 2130.
  • 23
    The flexibilities of the UNAIDS/WHO guidance can be seen, for example, in the decision by the Phambili vaccine trial in Johannesburg to offer voluntary medical male circumcision (VMMC) without a national policy being in place in South Africa.
  • 24
    S. Philpott, L. Heise & E. McGrory, et al. The challenge of defining standards of prevention in HIV prevention trials. Journal of Medical Ethics 2011; 37: 244248.
  • 25
    K. Shapiro & S.R. Benatar. HIV prevention research and global inequality: steps towards improved standards of care. Journal of Medical Ethics 2005; 31: 3947.
  • 26
    Abdool Karim et al. op. cit. note 3.
  • 27
    Microbicides Trial Network. MTN Statement on Decision to Discontinue Use of Oral Tenofovir Tablets in VOICE, a Major HIV Prevention Study in Women. September 28, 2011. Pittsburgh, PA: MTN. Available at: http://www.mtnstopshiv.org/node/3619 [Accessed 18 Feb 2013]. Microbicides Trial Network. MTN Statement on Decision to Discontinue Use of Tenofovir Gel in VOICE, a Major HIV Prevention Study in Women. Nov 25, 2011. Pittsburgh, PA: MTN Available at: http://www.mtnstopshiv.org/node/3909 [Accessed 18 Feb 2013]. The TDF/FTC arm in the VOICE trial is continuing, and results are expected in early 2013.
  • 28
    Grant et al. op. cit. note 3; P.L. Anderson et al. Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men. Science Translational Medicine 2012; 4.
  • 29
    Baeten et al. op. cit. note 3.
  • 30
    Thigpen et al. op. cit. note 3.
  • 31
    L. Van Damme et al. Preexposure Prophylaxis for HIV Infection among African Women. New Engl J Med 2012; 367: 411422.
  • 32
    Microbicides Trial Network. op. cit. note 24.
  • 33
    Van Damme et al. op. cit. note 22.
  • 34
    Microbicides Trial Network. MTN Statement on Decision to Discontinue Use of Oral Tenofovir Tablets in VOICE, a Major HIV Prevention Study in Women. September 28, 2011. Pittsburgh, PA: MTN. Available at: http://www.mtnstopshiv.org/node/3619 [Accessed 18 Feb 2013]. Microbicides Trial Network. MTN Statement on Decision to Discontinue Use of Tenofovir Gel in VOICE, a Major HIV Prevention Study in Women. Nov 25, 2011. Pittsburgh, PA: MTN Available at: http://www.mtnstopshiv.org/node/3909 [Accessed 18 Feb 2013]. The TDF/FTC arm in the VOICE trial is continuing, and results are expected in early 2013.
  • 35
    A. van der Straten, L. Van Damme, J.E. Haberer & D.R. Bangsberg. Unraveling the divergent results of pre-exposure prophylaxis trials for HIV prevention. AIDS. 2012 Apr 24; 26(7): F13F19. The promise of pre-exposure prophylaxis with antiretroviral drugs to prevent HIV transmission: a review. C.A. Hankins & M.R. Dybul. Curr Opin HIV AIDS. 2013 Jan; 8(1): 5058.
  • 36
    See FDA. 2012 Meeting Materials Antiviral Advisory Committee. May 11 2012 meeting of the Antiviral Drug Advisory Committee Questions to the committee available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM305774.pdf [Accessed 18 Feb 2013]; Transcript of meeting available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM311519.pdf [Accessed 18 Feb 2013]; All meeting materials available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/ucm295937.htm [Accessed 18 Feb 2013].
  • 37
    G. Gray, S. Buchbinder & A. Duerr. Overview of STEP and Phambili trial results: two phase IIb test-of-concept studies investigating the efficacy of MRK adenovirus type 5 gag/pol/nef subtype B HIV vaccine. Curr Opin HIV AIDS. 2010 Sep; 5(5): 357361.
  • 38
    Treatment Action Campaign (TAC). TAC Briefing on Adult and Adolescent Voluntary Medical Male Circumcision (VMMC). Capetown, South Africa:TAC. Available at: http://www.tac.org.za/community/node/3190 [Accessed 18 Feb 2013].
  • 39
    Auvert et al., op. cit. note 1. Bailey et al. op. cit. note 1. Gray et al. op. cit. note 1.
  • 40
    World Health Organization/UNAIDS. 2007. New Data on Male Circumcision and HIV Prevention: Policy and Programme Implications. Montreux, Switzerland. Available at: http://libdoc.who.int/publications/2007/9789241595988_eng.pdf [Accessed 18 Feb 2013].
  • 41
    New HIV Vaccine and Microbicides Advocacy Society (NHVMAS). 2012. Research Community Request For Better Process Of Community Engagement, Informed Consent And Standard Of Care In HIV Research In Nigeria. Lagos, Nigeria: NHVMAS. Available at: http://nhvmas-ng.org/website/eventcontent.php?eventid=%20141 [Accessed 18 Feb 2013].
  • 42
    For an example of effective community consultation, see A. Vallely et al. 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 2007; 7: 133.
  • 43
    M.O. Ukpong. Perspectives on Community Engagement in Standard of Prevention Package Negotiation for Clinical Trials. Presentation at the M2012 Symposium. Microbicide 2012, Sydney, Australia, USA. 15–19 April 2012.
  • 44
    Low literacy does not mean that people lack the capacity to understand research concepts, but it can pose communication challenges that require commitment to overcome. See P. Ndebele, D. Wassenaar, E. Munalula & F. Masiye. Improving understanding of clinical trial procedures among low literacy populations: an intervention within a microbicide trial in Malawi. BMC Medical Ethics 2012; 13: 29.
  • 45
    Ibid.
  • 46
    UNAIDS/AVAC. Good Participatory Practice Guidelines for Biomedical HIV Prevention Trials, 2nd ed. Geneva, Switzerland: UNAIDS/AVAC. Available at: http://www.unaids.org/en/media/unaids/contentassets/dataimport/pub/manual/2010/Guidelines_Biomedical_HIV_Prevention_2010_en.pdf. [Accessed 18 Feb 2013].
  • 47
    Ibid 35, 37.
  • 48
    Ukpong. op. cit. note 33.
  • 49
    P.B. Miller & C. Weijer. Fiduciary Obligation in Clinical Research. J Law Med Ethics 2006; 34: 424440.
  • 50
    M. Ukpong, op. cit. note 33.
  • 51
    At the time of writing, this issue was under review with regard to the French trial PrEP Ipergay. Ipergay tests episodic PrEP against a placebo comparator in men who have sex with men (MSM), and is being reviewed to determine whether this is ethically appropriate, given the evidence for PrEP efficacy and the FDA approval. http://www.ipergay.fr.
  • 52
    World Health Organisation. Guidance on oral pre-exposure prophylaxis (PrEP) for serodiscordant couples, men and transgender women who have sex with men at high risk of HIV: Recommendations for use in the context of demonstration projects. July, 2012. Geneva, Switzerland: WHO. Available at: http://www.who.int/hiv/pub/guidance_prep/en/index.html [Accessed 18 Feb 2013].
  • 53
    Ibid.
  • 54
    Discussion of alternative trial designs, such as those in which daily oral TDF/FTC PrEP is used as an active comparator, is beyond the scope of this article.
  • 55
    The HIV Vaccine Trials Network (HVTN) 505 Study currently taking place in the US is not yet providing oral TDF/FTC for PrEP to participants, but is offering information about it and monitoring drug levels. See HVTN 505: Expansion in Response to an Evolving Field. Seattle, WA: HVTN Available at: http://hvtnews.wordpress.com/2011/09/13/hvtn-505-expansion-in-response-to-an-evolving-field/ [Accessed 18 Feb 2013].
  • 56
    B. Haire. op. cit. note 1.