SUPPLEMENT ARTICLE
Bioethical Challenges With HIV Treatment as Prevention Jeremy Sugarman1,2,3 1
Berman Institute of Bioethics, Johns Hopkins University, 2School of Medicine, and 3Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
To best realize the opportunities afforded by treatment as prevention, important ethical challenges must be addressed, including those related to acceptability, safety, and effectiveness, as well as alternatives. Absent universal access to quality antiretroviral treatment, safety, fairness, and allocation must also be considered.
With mounting scientific evidence, substantial enthusiasm appropriately accompanies the use of human immunodeficiency virus (HIV) treatment as prevention (TasP) as a means of helping to curtail the HIV pandemic. As demonstrated by epidemiological and clinical research, the early treatment of HIV infection can have salutary effects not only for those treated but also in diminishing the chance of HIV transmission. In addition, TasP promises to diminish morbidity and mortality related to tuberculosis [1]. Accordingly, major efforts are being directed at implementing TasP. To best realize the opportunities afforded by TaSP, several important ethical challenges must be addressed. Some of these challenges relate to TaSP in general, while others are especially relevant due to the current lack of universal access to antiretroviral treatment (ART). ETHICS AND TASP TasP involves ethical issues related to acceptability, safety and effectiveness, as well as alternatives. Acceptability
Acceptability of initiating ART among both those who are infected with HIV and those who are not infected
Correspondence: Jeremy Sugarman, MD, MPH, MA, Johns Hopkins Berman Institute of Bioethics, 1809 Ashland Ave, Baltimore, MD 21205 ([email protected]). Clinical Infectious Diseases 2014;59(S1):S32–4 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected]. DOI: 10.1093/cid/ciu246
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and rely on TasP as a means of prevention is obviously critical in order for TasP to meet its dual goals of treatment and prevention. For those who are HIV infected, early treatment with ART may involve medicalization of infection prior to when they perceive themselves to be sick, which may be accompanied by reluctance to initiate treatment [2]. Since lifelong adherence is generally understood to be important in the treatment of HIV infection, it is essential that upon starting ART there is a genuine commitment to adhere as well as an ability to do so. As with all medical treatments, ART can have side effects that may be especially relevant in weighing the risks and benefits for particular individuals in deciding to initiate treatment. In addition to possible physical reactions to ART, in some settings social risks and stigma associated with treatment need to be considered. This range of concerns underscores the importance of informed and voluntary uptake of ART for TasP [3]. Since TasP aims to benefit not only the individuals being treated but also their sexual partners, it is necessary to consider the acceptability of TasP as a means of prevention for these partners. Considered as such, TasP is different from other forms of prevention in which atrisk individuals take some type of measure that is intended to afford a prevention benefit, such as ensuring condom use or using antiretroviral agents as preexposure prophylaxis (PrEP). In contrast, TasP is predicated on the actions of others. Therefore, uninfected individuals must trust that their HIV-infected sexual partners are adherent to ART and that the ART is sufficiently effective to mitigate transmission risk. While in some mutually monogamous dyadic relationships such trust
Downloaded from http://cid.oxfordjournals.org/ at University of Bath on October 30, 2014
Keywords. ethics; HIV prevention; HIV treatment; policy.
may be justified, in particular at-risk populations it may not, raising concerns about the safety and well-being of those at risk.
insulated to the extent possible from political whim and inevitable changes in economic conditions.
Safety and Effectiveness
Fairness
The safety and effectiveness of TasP is dependent upon having sound and reliable ART delivery systems. This includes the ability to provide appropriate care and monitoring at a reasonable cost. In addition, safety and effectiveness in preventing new infections will be influenced somewhat by risk behaviors; and perhaps to the certainty ascribed to the ability of TasP to prevent transmission of HIV [4]. Finally, while efficacy data regarding TaSP are convincing in dyadic heterosexual couples, effectiveness information in this setting is arguably lacking as are data in other at-risk populations.
While many communities would stand to derive substantial benefit from the implementation of TasP when universal access to ART is lacking, questions of fairness arise in determining where TasP should be initiated first. As TasP is implemented, further questions of fairness will arise in relation to which individuals will be selected for treatment. Although what precisely constitutes fairness at both of these levels is unclear and complex, it is essential that mechanisms of selection be procedurally fair and transparent [10].
Alternatives
CONSIDERATIONS DUE TO A LACK OF UNIVERSAL ACCESS TO ART Without universal access to quality ART, especially in resourcelimited settings, there are special ethical considerations related to safety, fairness, and allocation. While these considerations are largely emblematic of global disparities in wealth and power that will unfortunately not be easily resolved, they necessarily shape the contours of health-related programs such as TasP. Safety
Safety must be the initial consideration in initiating TasP. Although maintaining safety while on ART can be difficult in any setting, doing so in resource-poor settings where HIV prevalence is high can be expected to be especially challenging due to the need to ensure consistent access to suitable ART [9]. Similarly, it will be critical to establish context-appropriate systems of maintaining adherence and conducting monitoring. Moreover, these programs and processes need to be sustainable and
Across the globe, there are clear and unmet needs for access to HIV treatment and prevention services, not to mention other non-HIV–related global health priorities. At one level are concerns about the allocation of resources to ART- and non-ART–based means of HIV prevention. At another level are concerns about allocating ART for a variety of uses, such as treatment of those who are ill, early treatment of those who are infected for TasP, and prevention (including prevention of maternalto-child transmission [PMTCT], PrEP, and postexposure prophylaxis [PEP]). As long as there is true scarcity of ART, allocation decisions will be particularly difficult and it will be difficult to find easy answers. While some have advocated that when ART is scarce, priority should be given to treatment, then TasP, and then PrEP [11], others have illustrated the flaws of this intuitive conclusion [12–14]. It is beyond the scope of this article to examine the related arguments and counterarguments in detail, yet it is clear that additional attention needs to focus on the ethics of allocation. Recent scholarship in social justice theory [15, 16] may provide the necessary tools to help navigate appropriate paths forward. CONCLUDING COMMENTS TasP is an extremely promising means of helping to end the HIV pandemic. Nevertheless, like most, if not all, biomedical interventions, TasP involves ethical challenges that are exacerbated by global disparities in health, wealth, and the particular vulnerabilities of those infected with HIV and at heightened risk of becoming infected. Transparent and explicit deliberation about these issues along with meaningful engagement of the relevant stakeholders should help to address them in order to mitigate unintended actions and consequences as TasP is implemented. Notes Financial support. Work on this article was supported in part by the Johns Hopkins Center for AIDS Research, funded by the US National Institutes of Health (1P30AI094189).
Ethics and TasP
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In considering the use of TasP for the prevention of new infections, it is important to keep in mind that there are other evidence-based means of prevention, including other ART-based means, such as PrEP, and that no single approach to HIV prevention is likely to be sufficient [5]. Indeed, a combination of preventive measures is likely to be needed [6]. In addition, data are emerging regarding the possible safety and efficacy of alternative means of prevention, such as vaginal microbicides, that are within the control of at-risk individuals. Also, there are the aspirations of identifying an effective HIV vaccine that could afford durable prevention benefits that would not require assiduous adherence to ART [7]. Similarly, another aspirational approach relates to achieving an “HIV cure” [8] that, if realized in a way that could be practically implemented, would obviously provide profound benefits for treatment and in turn prevention.
Allocation
Supplement sponsorship. This article is published as part of a supplement entitled “Controlling the HIV Epidemic With Antiretrovirals,” sponsored by the International Association of Providers of AIDS Care. Potential conflict of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References
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Downloaded from http://cid.oxfordjournals.org/ at University of Bath on October 30, 2014
1. World Health Organization. Antiretroviral treatment as prevention (TasP) of HIV and TB: 2012 update. WHO/HIV/2012.12. Geneva, Switzerland, 2012. Available at: http://whqlibdoc.who.int/hq/2012/ WHO_HIV_2012.12_eng.pdf. Accessed 30 November 2013. 2. Katz IT, Essien T, Marinda ET, et al. Antiretroviral therapy refusal among newly diagnosed HIV-infected adults. AIDS 2011; 25: 2177–81. 3. Haire B, Kaldor JM. Ethics of ARV based prevention: treatment-as-prevention and PrEP. Dev World Bioeth 2013; 13:63–9. 4. Simon AE, Wu AW, Lavori PW, Sugarman J. Preventive misconception: its nature, presence, and ethical implications for research. Am J Prev Med 2007; 32:370–4. 5. McNairy ML, Howard AA, El-Sadr WM. Antiretroviral therapy for prevention of HIV and tuberculosis: a promising intervention but not a panacea. J Acquir Immune Defic Syndr 2013; 63(Suppl 2):S200–7.
6. Fauci AS, Folkers GK. The world must build on three decades of scientific advances to enable a new generation to live free of HIV/AIDS. Health Aff (Millwood) 2012; 31:1529–36. 7. Bailey TC, Sugarman J. Social justice and HIV vaccine research in the age of pre-exposure prophylaxis and treatment as prevention. Curr HIV Res 2013; 11:473–80. 8. Towards an HIV cure: a global scientific strategy. International AIDS Society Scientific Working Group on HIV Cure - Deeks SG, Autran B, et al. Nat Rev Immunol 2012; 12:607–14. 9. Gallant JE, Mehta SH, Sugarman J. Universal antiretroviral therapy for HIV infection: should US treatment guidelines be applied to resourcelimited settings? Clin Infect Dis 2013; 57:884–7. 10. Haire B. Treatment-as-prevention needs to be considered in the just allocation of HIV drugs. Am J Bioeth 2011; 11:48–50. 11. Macklin R, Cowan E. Given financial constraints, it would be unethical to divert antiretroviral drugs from treatment to prevention. Health Aff (Millwood) 2012; 31:1537–44. 12. Brock DW, Wikler D. Ethical challenges in long-term funding for HIV/ AIDS. Health Aff (Millwood) 2009; 28:1666–76. 13. Rennie S. Ethical use of antiretroviral resources for HIV prevention in resource poor settings. Dev World Bioeth 2013; 13:79–86. 14. Singh JA. Antiretroviral resource allocation for HIV prevention. AIDS 2013; 27:863–5. 15. Powers M, Faden R. Social justice: the moral foundations of public health and health policy. New York: Oxford University Press, 2006. 16. Wolff J, de-Shalit A. Disadvantage. New York: Oxford University Press, 2007.
Bioethical Challenges With HIV Treatment as Prevention Jeremy Sugarman1,2,3 1
Berman Institute of Bioethics, Johns Hopkins University, 2School of Medicine, and 3Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
To best realize the opportunities afforded by treatment as prevention, important ethical challenges must be addressed, including those related to acceptability, safety, and effectiveness, as well as alternatives. Absent universal access to quality antiretroviral treatment, safety, fairness, and allocation must also be considered.
With mounting scientific evidence, substantial enthusiasm appropriately accompanies the use of human immunodeficiency virus (HIV) treatment as prevention (TasP) as a means of helping to curtail the HIV pandemic. As demonstrated by epidemiological and clinical research, the early treatment of HIV infection can have salutary effects not only for those treated but also in diminishing the chance of HIV transmission. In addition, TasP promises to diminish morbidity and mortality related to tuberculosis [1]. Accordingly, major efforts are being directed at implementing TasP. To best realize the opportunities afforded by TaSP, several important ethical challenges must be addressed. Some of these challenges relate to TaSP in general, while others are especially relevant due to the current lack of universal access to antiretroviral treatment (ART). ETHICS AND TASP TasP involves ethical issues related to acceptability, safety and effectiveness, as well as alternatives. Acceptability
Acceptability of initiating ART among both those who are infected with HIV and those who are not infected
Correspondence: Jeremy Sugarman, MD, MPH, MA, Johns Hopkins Berman Institute of Bioethics, 1809 Ashland Ave, Baltimore, MD 21205 ([email protected]). Clinical Infectious Diseases 2014;59(S1):S32–4 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected]. DOI: 10.1093/cid/ciu246
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and rely on TasP as a means of prevention is obviously critical in order for TasP to meet its dual goals of treatment and prevention. For those who are HIV infected, early treatment with ART may involve medicalization of infection prior to when they perceive themselves to be sick, which may be accompanied by reluctance to initiate treatment [2]. Since lifelong adherence is generally understood to be important in the treatment of HIV infection, it is essential that upon starting ART there is a genuine commitment to adhere as well as an ability to do so. As with all medical treatments, ART can have side effects that may be especially relevant in weighing the risks and benefits for particular individuals in deciding to initiate treatment. In addition to possible physical reactions to ART, in some settings social risks and stigma associated with treatment need to be considered. This range of concerns underscores the importance of informed and voluntary uptake of ART for TasP [3]. Since TasP aims to benefit not only the individuals being treated but also their sexual partners, it is necessary to consider the acceptability of TasP as a means of prevention for these partners. Considered as such, TasP is different from other forms of prevention in which atrisk individuals take some type of measure that is intended to afford a prevention benefit, such as ensuring condom use or using antiretroviral agents as preexposure prophylaxis (PrEP). In contrast, TasP is predicated on the actions of others. Therefore, uninfected individuals must trust that their HIV-infected sexual partners are adherent to ART and that the ART is sufficiently effective to mitigate transmission risk. While in some mutually monogamous dyadic relationships such trust
Downloaded from http://cid.oxfordjournals.org/ at University of Bath on October 30, 2014
Keywords. ethics; HIV prevention; HIV treatment; policy.
may be justified, in particular at-risk populations it may not, raising concerns about the safety and well-being of those at risk.
insulated to the extent possible from political whim and inevitable changes in economic conditions.
Safety and Effectiveness
Fairness
The safety and effectiveness of TasP is dependent upon having sound and reliable ART delivery systems. This includes the ability to provide appropriate care and monitoring at a reasonable cost. In addition, safety and effectiveness in preventing new infections will be influenced somewhat by risk behaviors; and perhaps to the certainty ascribed to the ability of TasP to prevent transmission of HIV [4]. Finally, while efficacy data regarding TaSP are convincing in dyadic heterosexual couples, effectiveness information in this setting is arguably lacking as are data in other at-risk populations.
While many communities would stand to derive substantial benefit from the implementation of TasP when universal access to ART is lacking, questions of fairness arise in determining where TasP should be initiated first. As TasP is implemented, further questions of fairness will arise in relation to which individuals will be selected for treatment. Although what precisely constitutes fairness at both of these levels is unclear and complex, it is essential that mechanisms of selection be procedurally fair and transparent [10].
Alternatives
CONSIDERATIONS DUE TO A LACK OF UNIVERSAL ACCESS TO ART Without universal access to quality ART, especially in resourcelimited settings, there are special ethical considerations related to safety, fairness, and allocation. While these considerations are largely emblematic of global disparities in wealth and power that will unfortunately not be easily resolved, they necessarily shape the contours of health-related programs such as TasP. Safety
Safety must be the initial consideration in initiating TasP. Although maintaining safety while on ART can be difficult in any setting, doing so in resource-poor settings where HIV prevalence is high can be expected to be especially challenging due to the need to ensure consistent access to suitable ART [9]. Similarly, it will be critical to establish context-appropriate systems of maintaining adherence and conducting monitoring. Moreover, these programs and processes need to be sustainable and
Across the globe, there are clear and unmet needs for access to HIV treatment and prevention services, not to mention other non-HIV–related global health priorities. At one level are concerns about the allocation of resources to ART- and non-ART–based means of HIV prevention. At another level are concerns about allocating ART for a variety of uses, such as treatment of those who are ill, early treatment of those who are infected for TasP, and prevention (including prevention of maternalto-child transmission [PMTCT], PrEP, and postexposure prophylaxis [PEP]). As long as there is true scarcity of ART, allocation decisions will be particularly difficult and it will be difficult to find easy answers. While some have advocated that when ART is scarce, priority should be given to treatment, then TasP, and then PrEP [11], others have illustrated the flaws of this intuitive conclusion [12–14]. It is beyond the scope of this article to examine the related arguments and counterarguments in detail, yet it is clear that additional attention needs to focus on the ethics of allocation. Recent scholarship in social justice theory [15, 16] may provide the necessary tools to help navigate appropriate paths forward. CONCLUDING COMMENTS TasP is an extremely promising means of helping to end the HIV pandemic. Nevertheless, like most, if not all, biomedical interventions, TasP involves ethical challenges that are exacerbated by global disparities in health, wealth, and the particular vulnerabilities of those infected with HIV and at heightened risk of becoming infected. Transparent and explicit deliberation about these issues along with meaningful engagement of the relevant stakeholders should help to address them in order to mitigate unintended actions and consequences as TasP is implemented. Notes Financial support. Work on this article was supported in part by the Johns Hopkins Center for AIDS Research, funded by the US National Institutes of Health (1P30AI094189).
Ethics and TasP
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Downloaded from http://cid.oxfordjournals.org/ at University of Bath on October 30, 2014
In considering the use of TasP for the prevention of new infections, it is important to keep in mind that there are other evidence-based means of prevention, including other ART-based means, such as PrEP, and that no single approach to HIV prevention is likely to be sufficient [5]. Indeed, a combination of preventive measures is likely to be needed [6]. In addition, data are emerging regarding the possible safety and efficacy of alternative means of prevention, such as vaginal microbicides, that are within the control of at-risk individuals. Also, there are the aspirations of identifying an effective HIV vaccine that could afford durable prevention benefits that would not require assiduous adherence to ART [7]. Similarly, another aspirational approach relates to achieving an “HIV cure” [8] that, if realized in a way that could be practically implemented, would obviously provide profound benefits for treatment and in turn prevention.
Allocation
Supplement sponsorship. This article is published as part of a supplement entitled “Controlling the HIV Epidemic With Antiretrovirals,” sponsored by the International Association of Providers of AIDS Care. Potential conflict of interest. Author certifies no potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
References
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Downloaded from http://cid.oxfordjournals.org/ at University of Bath on October 30, 2014
1. World Health Organization. Antiretroviral treatment as prevention (TasP) of HIV and TB: 2012 update. WHO/HIV/2012.12. Geneva, Switzerland, 2012. Available at: http://whqlibdoc.who.int/hq/2012/ WHO_HIV_2012.12_eng.pdf. Accessed 30 November 2013. 2. Katz IT, Essien T, Marinda ET, et al. Antiretroviral therapy refusal among newly diagnosed HIV-infected adults. AIDS 2011; 25: 2177–81. 3. Haire B, Kaldor JM. Ethics of ARV based prevention: treatment-as-prevention and PrEP. Dev World Bioeth 2013; 13:63–9. 4. Simon AE, Wu AW, Lavori PW, Sugarman J. Preventive misconception: its nature, presence, and ethical implications for research. Am J Prev Med 2007; 32:370–4. 5. McNairy ML, Howard AA, El-Sadr WM. Antiretroviral therapy for prevention of HIV and tuberculosis: a promising intervention but not a panacea. J Acquir Immune Defic Syndr 2013; 63(Suppl 2):S200–7.
6. Fauci AS, Folkers GK. The world must build on three decades of scientific advances to enable a new generation to live free of HIV/AIDS. Health Aff (Millwood) 2012; 31:1529–36. 7. Bailey TC, Sugarman J. Social justice and HIV vaccine research in the age of pre-exposure prophylaxis and treatment as prevention. Curr HIV Res 2013; 11:473–80. 8. Towards an HIV cure: a global scientific strategy. International AIDS Society Scientific Working Group on HIV Cure - Deeks SG, Autran B, et al. Nat Rev Immunol 2012; 12:607–14. 9. Gallant JE, Mehta SH, Sugarman J. Universal antiretroviral therapy for HIV infection: should US treatment guidelines be applied to resourcelimited settings? Clin Infect Dis 2013; 57:884–7. 10. Haire B. Treatment-as-prevention needs to be considered in the just allocation of HIV drugs. Am J Bioeth 2011; 11:48–50. 11. Macklin R, Cowan E. Given financial constraints, it would be unethical to divert antiretroviral drugs from treatment to prevention. Health Aff (Millwood) 2012; 31:1537–44. 12. Brock DW, Wikler D. Ethical challenges in long-term funding for HIV/ AIDS. Health Aff (Millwood) 2009; 28:1666–76. 13. Rennie S. Ethical use of antiretroviral resources for HIV prevention in resource poor settings. Dev World Bioeth 2013; 13:79–86. 14. Singh JA. Antiretroviral resource allocation for HIV prevention. AIDS 2013; 27:863–5. 15. Powers M, Faden R. Social justice: the moral foundations of public health and health policy. New York: Oxford University Press, 2006. 16. Wolff J, de-Shalit A. Disadvantage. New York: Oxford University Press, 2007.
