Exploring the impact and cost-effectiveness of a vaccine as part of the Enhanced UNAIDS Investment Framework to end AIDS
Arne Näveke1, Emily Donaldson2, Chaitra Gopalappa3, Kevin Fisher2, Thomas Harmon1, Margaret McGlynn1, John Stover3, Yu Teng3, Mitchell Warren2
1International AIDS Vaccine Initiative, New York, NY, United States, 2AVAC, New York, NY, United States, 3Futures Institute, Glastonbury, CT, United States
Background: An enhanced UNAIDS Investment Framework reflecting 2013 WHO treatment guidelines modeled how scaling up existing treatment and prevention options, and adding new prevention tools including a vaccine, could reduce new HIV infections and AIDS-related deaths until 2050. A new study expands on this work by exploring the impact of key characteristics of an AIDS vaccine and a vaccination program on the potential reduction of new HIV infections as well as on cost-effectiveness as a major criterion for policy makers to consider access within public health programs. Methods: An epidemiological model was used to project the impact of adding vaccines of various characteristics in 24 low- and middle-income countries (LMICs) against a backdrop of different scenarios of scale-up of existing interventions. Characteristics explored include vaccine efficacy, duration of protection, uptake and cost. Results: Vaccines under all scenarios strongly reduce HIV incidence, with more efficacious vaccines of longer protection providing greatest benefit. Vaccination would be cost-effective in a wide range of scenarios depending on level of efficacy, duration of protection, uptake and cost per regimen. Conclusions: With existing and other emerging treatment and prevention options, an AIDS vaccine has the potential to achieve and sustain the end of AIDS. These data provide strong evidence for sustained research and development of efficacious, durable, and easy-to-implement AIDS vaccines at acceptable cost as part of a comprehensive response.
The current response to HIV/AIDS has reduced deaths and new infections. In order to eliminate the burden of the disease and lower the cost incurred by donors and affected countries in a sustainable manner, new infections must be reduced more dramatically. Studies have shown that a vaccine can be developed to help prevent HIV infection.  Recent discoveries should enable vaccines with broader and longer-lasting efficacy.  Sustained commitment is needed to overcome remaining scientific issues and translate new discoveries into effective and accessible vaccines.
While the ultimate profile, cost and timeline of an AIDS vaccine remain unknown, models can project a vaccine’s potential value to inform advocacy, investment decisions, and public policies around research and future access, while providing context to guide scientific decisions prioritizing product characteristics that directly influence potential impact and cost-effectiveness.
IAVI and the Futures Institute previously developed a model to estimate the impact of vaccines on HIV/AIDS. The model was incorporated into Spectrum modeling software, which includes demographic and HIV/AIDS modules, and which utilizes accessible inputs such as UNAIDS surveillance data and demographic and health surveys. 
A modeling exercise led by UNAIDS and including experts in modeling, policy, and research toward new prevention technologies (NPTs) led to an enhancement of the Investment Framework (IFE) first proposed by UNAIDS in 2011 to maximize the impact in LMICs to end AIDS. The IFE incorporated updated WHO guidelines for the initiation of antiretroviral treatment (ART) and explored the potential impact of NPTs such as treatment as prevention (TasP), topical and oral pre-exposure prophylaxis (PrEP), and vaccines to further the potential gains of scaling up existing interventions. 
Preliminary data from vaccine-specific follow-on modeling in partnership by IAVI, AVAC, and Futures Institute further explored the impact of basic product and implementation characteristics of a vaccine on new HIV infections and cost-effectiveness. This data was shared with the WHO, the Bill & Melinda Gates Foundation, (BMGF) the International AIDS Society (IAS) as well as other product development partnerships.
Assumptions were expanded and refined after consultations with experts in vaccine delivery as well as in HIV/AIDS programs, including the GAVI Alliance, the Global Fund to Fight AIDS, TB, and Malaria, the Wits Reproductive Health and HIV Institute, BMGF and with AIDS prevention and/or vaccine researchers in sub-Saharan Africa, including KAVI Institute of Clinical Research, Uganda Virus Research Institute and Aurum Institute.
A review of existing literature on access to vaccines and HIV/AIDS interventions and associated costs further informed assumptions.
Vaccine characteristics were varied to explore the relative impact on reducing new infections and cost-effectiveness. An analysis of the cost per Quality Adjusted Life Year (QALY) was performed utilizing the cost assumptions as outlined in Table 2 and guidelines for cost-effectiveness from the Commission on Macroeconomics and Health for cost-effectiveness in low-income countries (LICs) and middle-income countries (MICs). 
This analysis explored the impact that an AIDS vaccine could have in three scenarios:
Current Trends – Recent progress in reducing new HIV infections continues but plateaus as additional resources required to sustain recent aggressive scale-up of programs are not made available. Progress in reducing new infections is offset by population growth.
Full IFE implementation –Target coverage levels for existing treatment and prevention options for LMICs are achieved by 2020. Treatment coverage reflects the 2013 WHO guidelines.
50% Implementation of IFE – Coverage with existing interventions reaches 50% of IFE targets by 2020.
Results are summarized in Figure 1. Under base assumptions (Table 1), a vaccine reduces annual infections with HIV by 78-85% depending on background scenario, approaching “Zero” new infections. Cumulative infections from 2027 to 2070 are reduced by 36-45%.
Figure 2 summarizes an analysis illustrating sensitivity to vaccine efficacy using the IFE scenario. A vaccine with 30% efficacy would still reduce the number of new infections in 2070 by nearly half.
A vaccine’s cost-effectiveness depends on a number of factors, including its efficacy, background HIV incidence, and the scale-up of other HIV/AIDS prevention options.
Figure 3 illustrates that a vaccine with Base characteristics would be cost-effective (less than 3 times the average Gross National Income (GNI) based on purchasing power parity per capita) in LICs under any cost per regimen modeled in both the IFE and 50% scale-up scenarios. In order to be considered highly cost-effective (less than 1 times the average GNI per capita) compared to the cost of scale-up, cost per vaccine regimen would need to be below $20-25 under full IFE scale-up and $35-40 under 50% IFE scale-up.
The introduction of an AIDS vaccine with product and implementation characteristics comparable to those for other recently introduced vaccines would strongly accelerate progress in reducing new HIV infections in LMICs, even with high scale-up of existing HIV/AIDS interventions (IFE). However, key product characteristics and cost per regimen will significantly influence a vaccine’s impact and accessibility through public health programs.
These data strongly support sustained commitment to continued and accelerated AIDS vaccine research and development even as ambitious goals for scaling up HIV prevention, treatment, and care interventions are implemented. Any discussion of ending the AIDS epidemic must consider the role of a vaccine.
Preliminary analysis supports the following conclusions:
An AIDS vaccine represents an essential element of definitive HIV/AIDS prevention and treatment programs even if other prevention and treatment measures are well-implemented.
Vaccine research and development decisions should prioritize characteristics that will drive a vaccine’s acceptability to public health authorities and program implementers.
1. Rerks-Ngarm et al. “Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand.” N Engl J Med 2009; 361:2209-20.
2. Excler et al. “HIV-1 vaccines: Challenges and new perspectives. Hum Vaccin Immunother. 2014 Jun 1;10(6):1734-1746. Epub 2014 Mar 17. Review.
3. IAVI. 2006 “The Impact of an AIDS Vaccine in Developing Countries: A New Model and Preliminary Results.” Policy Research Working Paper #8. New York.
4. Stover et al. 2014. “How can we get close to Zero? The potential contribution of biomedical prevention and the investment framework towards an effective response to HIV.” Accepted for publication by PLoS One.
5. World Health Organization. “Cost-effectiveness thresholds” http://www.who.int/choice/costs/CER_thresholds/en. Accessed October 20, 2014
Spectrum is freely available for download online at www.FuturesInstitute.org