Consequences of a changing US strategy in the global HIV investment landscape

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HIV in 2015, over half lacked access to lifesaving antiretroviral therapy [2]. If donor countries pull back from the global response now, this opportunity to reach a turning point will be lost, risking backsliding into a resurgent epidemic.
In the landscape of global health and development expenditures [3], the United States is the largest donor to the fight against HIV by virtue of the President's Emergency Plan for AIDS Relief (PEPFAR) and contributions to the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Proposed in 2003 by President George W. Bush, PEPFAR fundamentally altered the course of the HIV epidemic and is currently supporting nearly 11.5 million people on antiretroviral treatment in developing countries. The United States is also the biggest contributor to the Global Fund, the world's largest public-private funder for HIV, tuberculosis, and malaria. PEPFAR and the Global Fund are complementary, interreliant, and vital leaders of the global AIDS response [4].
Recently, the US Office of Management and Budget proposed a federal budget blueprint for the fiscal year of 2018 that reduces funding to foreign aid and states an intention to provide 'sufficient resources to maintain current commitments and all current patient levels on HIV/AIDS treatment under PEPFAR' [5].
Several studies have described the impact of US investments in stabilizing or reducing HIV incidence, but many are retrospective, qualitative, small in scope, or focused on individual funding streams or interventions [6][7][8][9]. Most substantive are the ongoing Populationbased HIV Impact Assessments Project, which in 2016 reported decreasing HIV incidence in three PEPFARrecipient countries [10], and a Lancet commission that estimated the costs of several global health investment scenarios [11]. However, uncertainty regarding US global health investments warrants an examination of both the investment counterfactual and the projected long-term impact of changes to the US strategy -broad policy questions for which mathematical modeling is a powerful tool. We apply a mathematical model [12] (summarized in Appendix pg. 1-3, http://links.lww.com/QAD/B179) to build a comprehensive picture of the impact of US investment across Sub-Saharan Africa, which accounts for 70% of the global HIV burden and where many countries have insufficient domestic resources to meet long-term treatment needs [13]. We describe how the HIVepidemic might have progressed in Sub-Saharan Africa if the United States had failed to invest, how the epidemic is likely to evolve under several scenarios for future US funding decisions, and explore the relative impact of a shift away from key at-risk populations.
Since 2003, the Global Fund and PEPFAR have funded treatment delivery, supported testing and counseling services, played a role in lowering the cost of antiretroviral drugs, scaled up HIV prevention by spearheading voluntary medical male circumcision and other prevention programs, and encouraged implementing countries to increase their domestic HIV spending. We constructed a historical counterfactual using financial data to depict the loss of these contributions if PEPFAR and the Global Fund were never founded (Appendix pg. 3-6, http:// links.lww.com/QAD/B179). It was assumed in this case that behavior change initiatives would have been limited, domestic investments lower, and antiretroviral therapy persistently expensive. Although it is possible that US investment has suppressed, rather than encouraged, increases in domestic contributions [14], this remains under debate [15,16] and governments might have faced high opportunity costs in attempting to increase domestic HIV spending by redirecting funds from other health initiatives. Under this worst-case counterfactual, the model shows that mortality would not have begun to decline in the mid-2000s but instead would have continued to increase. This would have directly resulted in 3.7 million more HIV infections by the end of 2016, and nearly five million more people dead of AIDS-related causes, relative to what has occurred ( Fig. 1a-c).
Sustained progress toward global targets set by the Joint United Nations Program on HIV/AIDS (UNAIDS) [1] will require the continued rapid expansion of antiretroviral therapy in concert with the prevention of new HIV infections [17]. Three factors will drive the impact that can be achieved by future treatment and prevention efforts: the amount of funding contributed by the United States and other donors, the degree to which governments of implementing countries increase their domestic financing, and policies determining how available resources are spent. We have developed a series of modeling scenarios to explore these drivers (Appendix pg. 7-12, http://links.lww.com/QAD/B179). The results are summarized in Table 1  As a second scenario, the United States could increase investment by 10% in PEPFAR and the Global Fund, while maintaining current spending patterns. In this scenario, we assume that other international funds remain flat, funding is distributed to countries according to present patterns, governments of implementing countries grow their own HIV spending only in line with economic trends, and prevention interventions are rolled out nationally (Appendix pg. 8-10, http://links.lww.com/ QAD/B179). In this case, we estimate that the total HIV Impact of US investment in global HIV McGillen et al. funding envelope will be $116 billion over the next 15 years. This will enable provision of treatment to 66% of adults living with HIV and avert 12.5 million HIV infections and more than one million AIDS deaths relative to no expansion of programs. Compared with 2010 numbers, these are reductions of 40 and 73% in new HIV infections and AIDS deaths, respectively.
Alternatively, the 10% increase in United States spending may be accompanied by governments of implementing countries increasing their own domestic HIV spending to meet an ambitious target developed by Resch et al. [18] and based on the HIV share of the disease burden (Appendix pg. 10-11, http://links.lww.com/QAD/ B179). In this case, the total HIV budget will be $146 billion, enabling 77% of adults living with HIV to be virally suppressed on treatment and averting 18 million HIV infections and 1.9 million AIDS deaths relative to no further program expansion. These are reductions of 67% in HIV infections and 82% in AIDS deaths compared with 2010 numbers. Thus, against a backdrop of increased US funding, governments of affected countries can avert 44% more infections and 26% more deaths by moving from status-quo to ambitious HIV spending. However, even this level of response will not reach UNAIDS targets without improvements in how funds are allocated to population groups and prevention interventions.
Our final scenario explores an idealized HIV response whereby the United States both increases its present investment level by 10% and leads a concerted effort to optimize the channeling of prevention resources. In this case, funds are allocated to prevention portfolios that are optimized to subnational epidemiology (maximizing infections averted for the lowest cost) and specifically target key at-risk populations (Appendix pg. 11-12, http://links.lww.com/QAD/B179). This is in line with PEPFAR's 'right things, right places, right time' policy of making high-impact programs responsive to the people at greatest risk and in high-burden places [19]. For a funding envelope of $146 billion, we find that this approach will enable 83% of adults living with HIV to be virally suppressed on treatment and avert 22 million HIV infections and 2.3 million AIDS deaths over the 15-year period, relative to no further program expansion. These are reductions on 2010 levels of 88% for HIV infections and 87% for AIDS deaths. This strategy comes closest by the end of the 15-year period to achieving the UNAIDS targets of 95-95-95 for treatment (95% of people living with HIV knowing their status, 95% of those diagnosed receiving treatment, and 95% of those receiving treatment having viral suppression) and 90% reductions in new infections and deaths relative to 2010 numbers [1]. Using investments optimally (Appendix pg. 11-12, http:// links.lww.com/QAD/B179) can thus avert 52% more infections and 17% more AIDS deaths than the same amount of funding used less efficiently.
These findings are supported by a large body of costeffectiveness studies that indicate good returns on HIV investment in many settings (for example, [20][21][22]  strengthening [23]. We have, therefore, likely underestimated the impact of US investments in HIV. We also note that the impact described herein may be achieved by multiple donor countries and implementing governments, rather than by a unilateral increase in US investments.
Our validated model has enabled us to measure both the historical impact of US investment and its plausible future impact under several scenarios -and we have found that if the United States and other donors choose to amplify their HIV response in concert with strong domestic support in developing countries, the world can approach UNAIDS targets for ending the epidemic. This analysis contributes one piece of a larger decision process which enables policy makers to synthesize a wide range of evidence in a formal way, and will, we hope, help to inform public debate and the choice facing those who will decide the US foreign aid HIV budget and strategy going forward.