Antiretroviral resource allocation for HIV prevention

In July 2012, the US Food and Drug Administration (FDA) endorsed its Antiviral Products Advisory Committee's recommendation [1] and changed the indication of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC or Truvada) to include pre-exposure prophylaxis (PrEP), to reduce the risk of sexually acquired HIV-1 in adults [2]. Shortly thereafter, the WHO published guidance on oral PrEP for serodiscordant couples, men and transgender women who have sex with men at high risk of HIV for use in the context of demonstration projects [3]. Both developments followed the South African Medicine Control Council's long-awaited approval in May 2012 of the CAPRISA 008 trial, which aims to assess the implementation, effectiveness and safety of tenofovir gel provision to the participants of the CAPRISA 004 study through family planning services in KwaZulu-Natal, South Africa [4]. But these significant developments will amount to nought if we buy the short-sighted and flawed argument that it would be unethical to divert antiretroviral drugs from treatment to prevention given resource constraints when there are currently insufficient antiretroviral drugs to treat those living with HIV [5]. Realizing the goal of an AIDS-free generation requires antiretroviral deployment for treatment and prevention [6]. In fact, denying antiretroviral provision for prevention efforts is unethical and a transgression of human rights. The treatment versus prevention debate Commentators such as Macklin and Cowan argue that in many resource-poor settings, diverting a substantial portion of antiretroviral drugs to prevention could result in a shortage for people who are medically eligible for treatment. They conclude that it is unethical to ‘deliberately watch patients with treatable HIV/AIDS worsen and die, even with supportive care, if medications for treatment are diverted to PrEP’. They support this position by arguing that patients who have HIV/AIDS but whose disease is in early stages have a ‘virtual certainty of benefiting’ from antiretroviral drugs while ‘much greater uncertainty surrounds the benefits for prevention’ with PrEP given that the ‘effectiveness of that method depends on constant and appropriate use by people who engage in high-risk behaviour’. They argue that as long as antiretrovirals need to be allocated between prevention and treatment, first priority should be given to treatment, and second priority to the treatment-as-prevention (TasP) strategy. They also argue that until testing is broadly expanded, using antiretroviral drugs for prevention can have only a limited impact on slowing the spread of HIV/AIDS in highly affected communities. This is in contrast to other commentators, such as Brock and Wikler, who have argued that ‘the strongest moral imperative directs us to give priority to saving the most lives …even if this means lowering the priority given to the goal of universal access to treatment, to provide maximum protection from HIV infection’ [7]. However, antiretroviral resource allocation need not be reduced to a simplistic treatment versus prevention dichotomy. Instead, antiretroviral resource allocation for both treatment and prevention needs to occur simultaneously in an incrementally sustainable manner and concurrent to a sustained expanded HIV counselling and testing (HCT) programme. Why denying antiretroviral provision for prevention efforts is unethical The principles of stewardship, responsibility, harm prevention, solidarity, and compassion dictate that authorities have a duty to protect the interests of all people, particularly the most vulnerable, regardless of the prevailing cultural, social, political, moral or even policy/legal norms. In high HIV-burden settings such as sub-Saharan Africa, young women are disproportionately affected by the HIV epidemic [8]. Subjected to patriarchal norms, young women are typically disempowered and unable to negotiate condom use with their male sexual partners. Young women are also less likely to know their HIV status and to access treatment. Thus, restricting antiretroviral resource allocation to only treatment effectively leaves the fate of such women dependent on the conscience and actions of their male sexual partners and deprives women of their autonomy and dignity. Such a strategy is irresponsible and unethical. From an ethics perspective, the Prioritarian principle holds that resources must be directed to the least advantaged members or groups in society. The principles of Urgent Need and Duty of Rescue dictate that those at high risk of HIV infection and who are unable to protect themselves from infection must be provided with relevant interventions to prevent or mitigate their chance of being infected. These principles speak to the ethical imperative of providing HIV-infected individuals with treatment, and uninfected vulnerable individuals in urgent need of protection from HIV, with interventions such as PrEP. The landmark HPTN 052 trial suggests that if a sero-positive partner in a sero-discordant relationship enjoys treatment access, their sero-negative partner's chances of acquiring HIV is drastically lowered [9]. Accordingly, it has been argued that as a TasP strategy serves the dual goal of treatment and prevention, it should be preferred over the allocation of antiretroviral drugs for PrEP, should the efficacy of PrEP interventions be confirmed [10]. This argument is also flawed. Participants in the HPTN 052 study were sero-discordant couples, many of whom were in stable monogamous relationships in whom antiretroviral treatment could supplement condom use for prevention of HIV transmission. Such a strategy may not work in instances of multiple concurrent sexual relationships. Furthermore, such a strategy will only be effective if individuals know their HIV status, qualify for treatment and rigidly adhere to their treatment regimens once they are diagnosed with HIV and initiated on treatment, if eligible. Such factors are challenging to satisfy in most settings with high HIV burdens and would present challenges to major scale-up of couple testing and counselling. Thus, expecting TasP to be a panacea for treatment and prevention in such a context is unrealistic. This again speaks to an ethical imperative for providing PrEP access, irrespective of, or concurrent to, a TasP strategy. Of course, similar challenges apply to treatment and PrEP too. For instance, on-going HIV testing, counselling and adherence would also be crucial to the success of PrEP. Policymakers will thus have to carefully plan how to counter these challenges prospectively in both TasP and PrEP programmes. Why ARV deployment for prevention efforts is a human rights obligation The International Covenant on Economic, Social and Cultural Rights (ICESCR) which has been ratified by almost all countries globally, introduced the concept of a state's ‘minimum core obligation’ in respect to its citizens [11]. If a state fulfils its ‘minimum core obligations’ in relation to HIV management, its HIV management policies are arguably justifiable. If a country is experiencing stubborn or rising HIV prevalence, this could be indicative of that setting not meeting its minimum core obligations in relation to HIV management. Human rights jurisprudence dictates that inadequate policies that do not meet the standard of reasonableness necessitate revision [12]. Such revision may necessitate the adoption of novel strategies. But what constitutes a ‘minimum core obligation’ in the context of HIV prevention? A state's minimum core obligation in relation to HIV goes beyond facilitating condom access and counselling, especially in settings where vulnerable individuals are unable to access such interventions because of social, cultural, or legal factors. This again speaks to the important role of PrEP. But even if on-going trials demonstrate or confirm the efficacy and effectiveness of PrEP (topical and/or oral), because of resource constraints, all at-risk HIV-uninfected persons will not qualify for immediate PrEP access. Instead, policymakers may have to consider restricting PrEP access in the short to medium term to vulnerable individuals in ‘urgent need’, based on the contextual epidemic. Human rights doctrines would hold that such prioritization is equitable and reasonable. However, determining what constitutes ‘urgent need’ and who qualifies for this status will have to occur in a transparent manner to be ethically defensible. This will necessitate engagement between government HIV/AIDS technical advisory groups, health economists, policy experts, treasury officials, donors, health officials at all levels of government, social welfare officials, the scientific community, civil society, nongovernmental service providers (such as MSF), and constituents from potential target communities. These parties must consider localized epidemiological factors, logistical challenges, resource constraints, cost-effectiveness considerations, and potential impact in their deliberations. This process will help policymakers identify vulnerable groups for urgent, prioritized access, and strengthen the perceived fairness and legitimacy of the resulting prioritization ranking process and outcome. How to ensure sustainable programmatic implementation for treatment and prevention The notion of ‘Progressive Realization’ finds its genesis in article 2 of the ICESCR [12] and requires states to take steps, including the adoption of legislative measures, to the maximum of their available resources to achieve progressively the full realization of a recognized human right. A government's minimum core obligation in regard to the right to health in the context of HIV includes both the progressive provision of treatment and prevention interventions. This means that in high HIV-burden settings where programmatic treatment rollout has commenced, incremental treatment scale-up should continue concurrent to the engagement of stakeholders to fairly identify marginalized and high risk populations who are in urgent need of novel HIV prevention interventions. Once such cohorts are identified progressive PrEP rollout should commence. The rollout of new interventions should not compromise existing effective programmes. Instead, treatment rollout and PrEP rollout should occur simultaneously, and concurrent to a sustained and expanded HCT programme, and all role players should maximize their efforts to integrate HCT, treatment and prevention in an efficient and cost-effective way. Conclusion Framing antiretroviral resource allocation as a treatment versus prevention dichotomy is simplistic and counter-productive. Restricting antiretroviral drugs to only treatment is not only unethical; it also transgresses human rights norms. Our goal should be antiretroviral deployment for both treatment and prevention, simultaneous to expanded HCT programs as only this strategy will achieve UNAIDS's goal of high-impact, high-value strategies, and yield an AIDS-free generation. Acknowledgements J.A.S. participated in WHO consultations on ‘The Strategic Use of ARVs’,’ The ethics of PreP and ARVs for prevention: How should countries reach a decision?’ and ‘Programmatic Guidance of the 2013 Consolidated Guidelines on ARV-related Interventions’. The author wishes to thank Jocalyn Clark, Anant Bhan, Shane Green, Claudia Emerson, Jim Lavery, Blair Hanewall, Stephen Becker, Mark Dybul, and Ron Bayer for comments on earlier iterations of the manuscript. Funding: Jerome Amir Singh receives support from the Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa, which forms part of the Comprehensive International Programme on AIDS, funded by the US National Institute of Allergy and Infectious Diseases. He also receives support from the Ethical, Social, and Cultural Program for Global Health at the Sandra Rotman Centre, Toronto, Canada, which receives funding from the Bill and Melinda Gates Foundation. The funders had no role in study design, data collection and analysis, or decision to publish the manuscript. He also receives support from the HIV Prevention Trial Network, and the Ethical, Social, and Cultural Program for Global Health at the Sandra Rotman Centre, Toronto, Canada, which receives funding from the Bill and Melinda Gates Foundation. Conflicts of interest There are no conflicts of interest.

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