Treatment of HIV for the Prevention of Transmission in Discordant Couples and at the Population Level.

The scientific breakthrough proving that antiretroviral therapy (ART) can halt heterosexual HIV transmission came in the form of a landmark clinical trial conducted among serodiscordant couples. Study findings immediately informed global recommendations for the use of treatment as prevention in serodiscordant couples. The extent to which these findings are generalizable to other key populations or to groups exposed to HIV through nonsexual transmission routes (i.e., anal intercourse or unsafe injection of drugs) has since driven a large body of research. This review explores the history of HIV research in serodiscordant couples, the implications for management of couples, subsequent research on treatment as prevention in other key populations, and challenges in community implementation of these strategies.

Projected economic evaluation of the national implementation of a hypothetical HIV vaccination program among adolescents in South Africa, 2012.

BACKGROUND: Adolescents in South Africa are at high risk of acquiring HIV. The HIV vaccination of adolescents could reduce HIV incidence and mortality. The potential impact and cost-effectiveness of a national school-based HIV vaccination program among adolescents was determined. METHOD: The national HIV disease and cost burden was compared with (intervention) and without HIV vaccination (comparator) given to school-going adolescents using a semi-Markov model. Life table analysis was conducted to determine the impact of the intervention on life expectancy. Model inputs included measures of disease and cost burden and hypothetical assumptions of vaccine characteristics. The base-case HIV vaccine modelled cost at US$ 12 per dose; vaccine efficacy of 50 %; duration of protection of 10 years achieved at a coverage rate of 60 % and required annual boosters. Incremental cost-effectiveness ratios (ICER) were calculated using life years gained (LYG) serving as the outcome measure. Sensitivity analyses were conducted on the vaccine characteristics to assess parameter uncertainty. RESULTS: The HIV vaccination model yielded an ICER of US$ 5 per LYG (95 % CI ZAR 2.77-11.61) compared with the comparator, which is considerably less than the national willingness-to-pay threshold of cost-effectiveness. This translated to an 11 % increase in per capita costs from US$ 80 to US$ 89. National implementation of this intervention could potentially result in an estimated cumulative gain of 23.6 million years of life (95 % CI 8.48-34.3 million years) among adolescents age 10-19 years that were vaccinated. The 10 year absolute risk reduction projected by vaccine implementation was 0.42 % for HIV incidence and 0.41 % for HIV mortality, with an increase in life expectancy noted across all age groups. The ICER was sensitive to the vaccine efficacy, coverage and vaccine pricing in the sensitivity analysis. CONCLUSIONS: A national HIV vaccination program would be cost-effective and would avert new HIV infections and decrease the mortality and morbidity associated with HIV disease. Decision makers would have to discern how these findings, derived from local data and reflective of the South African epidemic, can be integrated into the national long term health planning should a HIV vaccine become available.

Funding HIV-vaccine research in developing countries-what is wrong with IAVI's recommendation?

The International AIDS Vaccine Initiative recommends targeting resources to research institutions in developing countries in order to accelerate the development of an effective HIV vaccine. In contrast, this paper shows that neither lump-sum nor in-kind transfers are an effective policy. We analyze several financing mechanisms as a means to overcome the lack of depth in HIV-vaccine research in a non-cooperative framework. At first, we point to cases in which financial support is actually counterproductive. Then we analyze whether in-kind transfers are preferable to lump-sum transfers. Even if donors prefer aid in kind because the incentives for moral hazard of recipients can be reduced, we demonstrate that it is effective only if recipients have cost advantages.

Is a HIV vaccine a viable option and at what price? An economic evaluation of adding HIV vaccination into existing prevention programs in Thailand.

BACKGROUND: This study aims to determine the maximum price at which HIV vaccination is cost-effective in the Thai healthcare setting. It also aims to identify the relative importance of vaccine characteristics and risk behavior changes among vaccine recipients to determine how they affect this cost-effectiveness. METHODS: A semi-Markov model was developed to estimate the costs and health outcomes of HIV prevention programs combined with HIV vaccination in comparison to the existing HIV prevention programs without vaccination. The estimation was based on a lifetime horizon period (99 years) and used the government perspective. The analysis focused on both the general population and specific high-risk population groups. The maximum price of cost-effective vaccination was defined by using threshold analysis; one-way and probabilistic sensitivity analyses were performed. The study employed an expected value of perfect information (EVPI) analysis to determine the relative importance of parameters and to prioritize future studies. RESULTS: The most expensive HIV vaccination which is cost-effective when given to the general population was 12,000 Thai baht (US$1 = 34 Thai baht in 2009). This vaccination came with 70% vaccine efficacy and lifetime protection as long as risk behavior was unchanged post-vaccination. The vaccine would be considered cost-ineffective at any price if it demonstrated low efficacy (30%) and if post-vaccination risk behavior increased by 10% or more, especially among the high-risk population groups. The incremental cost-effectiveness ratios were the most sensitive to change in post-vaccination risk behavior, followed by vaccine efficacy and duration of protection. The EVPI indicated the need to quantify vaccine efficacy, changed post-vaccination risk behavior, and the costs of vaccination programs. CONCLUSIONS: The approach used in this study differentiated it from other economic evaluations and can be applied for the economic evaluation of other health interventions not available in healthcare systems. This study is important not only for researchers conducting future HIV vaccine research but also for policy decision makers who, in the future, will consider vaccine adoption.

Multi-million dollar AIDS vaccine project cancelled.

Two years after calling for applications, the Government of Canada and the Bill & Melinda Gates Foundation decided not to proceed with a planned $88 million project to build an HIV vaccine plant, raising questions about what was behind the move.

Vaccine initiative money reallocated; emphasis placed on research and mother-to-child transmission.

When the federal government officially announced in February 2010 the cancellation of a CAN dollars 88 million project to establish a pilot-scale HIV vaccine manufacturing facility in Canada, it was unclear how the money would finally be used. However, in July the announcement came that the funds would be reallocated to research and to the prevention of mother-to-child transmission of HIV.

Africa boosts AIDS vaccine R&D.

Efforts have recently heated up in several African countries to tailor-make preparations that many believe offer the best hope yet for stopping HIV cold. But all are at the earliest stages, which means it will take years before a vaccine might prove its worth.

The past, present, and future of HIV prevention: integrating behavioral, biomedical, and structural intervention strategies for the next generation of HIV prevention.

In the past 25 years, the field of HIV prevention research has been transformed repeatedly. Today, effective HIV prevention requires a combination of behavioral, biomedical, and structural intervention strategies. Risk of transmitting or acquiring HIV is reduced by consistent male- and female-condom use, reductions in concurrent and/or sequential sexual and needle-sharing partners, male circumcision, and treatment with antiretroviral medications. At least 144 behavioral prevention programs have been found effective in reducing HIV transmission acts; however, scale up of these programs has not occurred outside of the United States. A series of recent failures of HIV-prevention efficacy trials for biomedical innovations such as HIV vaccines, treating herpes simplex 2 and other sexually transmitted infections, and diaphragm and microbicide barriers highlights the need for behavioral strategies to accompany biomedical strategies. This challenges prevention researchers to reconceptualize how cost-effective, useful, realistic, and sustainable prevention programs will be designed, delivered, tested, and diffused. The next generation of HIV prevention science must draw from the successes of existing evidence-based interventions and the expertise of the market sector to integrate preventive innovations and behaviors into everyday routines.

The future of a partially effective HIV vaccine: assessing limitations at the population level.

OBJECTIVES: Mathematical models have unanimously predicted that a first-generation HIV vaccine would be useful and cost-effective to roll out, but that its overall impact would be insufficient to reverse the epidemic. Here, we explore what factors contribute most to limiting the impact of such a vaccine. METHODS: Ranging from a theoretical ideal to a more realistic regimen, mirroring the one used in the currently ongoing trial in South Africa (HVTN 702), we model a nested hierarchy of vaccine attributes such as speed of scale-up, efficacy, durability, and return rates for booster doses. RESULTS: The predominant reasons leading to a substantial loss of vaccine impact on the HIV epidemic are the time required to scale up mass vaccination, limited durability, and waning of efficacy. CONCLUSIONS: A first-generation partially effective vaccine would primarily serve as an intermediate milestone, furnishing correlates of immunity and platforms that could serve to accelerate future development of a highly effective, durable, and scalable next-generation vaccine capable of reversing the HIV epidemic.

Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine regimen in South Africa.

BACKGROUND: RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective. METHODS: Consistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions. RESULTS: Our analysis shows that this partially effective vaccine could prevent, at catch-up vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750). CONCLUSIONS: While a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.

Competing biomedical HIV prevention strategies: potential cost-effectiveness of HIV vaccines and PrEP in Seattle, WA.

INTRODUCTION: Promising HIV vaccine candidates are steadily progressing through the clinical trial pipeline. Once available, HIV vaccines will be an important complement but also potential competitor to other biomedical prevention tools such as pre-exposure prophylaxis (PrEP). Accordingly, the value of HIV vaccines and the policies for rollout may depend on that interplay and tradeoffs with utilization of existing products. In this economic modelling analysis, we estimate the cost-effectiveness of HIV vaccines considering their potential interaction with PrEP and condom use. METHODS: We developed a dynamic model of HIV transmission among the men who have sex with men population (MSM), aged 15-64 years, in Seattle, WA offered PrEP and HIV vaccine over a time horizon of 2025-2045. A healthcare sector perspective with annual discount rate of 3% for costs (2017 USD) and quality-adjusted life years (QALYs) was used. The primary economic endpoint is the incremental cost-effectiveness ratio (ICER) when compared to no HIV vaccine availability. RESULTS: HIV vaccines improved population health and increased healthcare costs. Vaccination campaigns achieving 90% coverage of high-risk men and 60% coverage of other men within five years of introduction are projected to avoid 40% of new HIV infections between 2025 and 2045. This increased total healthcare costs by $30 million, with some PrEP costs shifted to HIV vaccine spending. HIV vaccines are estimated to have an ICER of $42,473/QALY, considered cost-effective using a threshold of $150,000/QALY. Results were most sensitive to HIV vaccine efficacy and future changes in the cost of PrEP drugs. Sensitivity analysis found ranges of 30-70% HIV vaccine efficacy remained cost-effective. Results were also sensitive to reductions in condom use among PrEP and vaccine users. CONCLUSIONS: Access to an HIV vaccine is desirable as it could increase the overall effectiveness of combination HIV prevention efforts and improve population health. Planning for the rollout and scale-up of HIV vaccines should carefully consider the design of policies that guide interactions between vaccine and PrEP utilization and potential competition.

Household demand for preventive HIV/AIDS vaccines in Thailand: do husbands' and wives' preferences differ?

OBJECTIVES: The aims of this study were to estimate household demand in the general population of Thailand for a (hypothetical) preventive HIV vaccine; to determine whether spouses in the same household would purchase the same number of vaccines for household members and have the same demand function; to determine whether spouses would allocate vaccines to the same household members; and to estimate household and per capita average willingness to pay (WTP) for an HIV vaccine price. METHODS: The data come from a national contingent valuation survey of 2524 residents (aged 18-20 years) of 1235 households in Thailand during the period 2000 to 2001. In a subsample of 561 households, both head of household and spouse completed independent (separate) interviews. Respondents were asked whether they would purchase an HIV vaccine for themselves and for other household members if one were available at a specified price. RESULTS: For the full sample, average household WTP for the vaccine was substantial (US$610 at 50% vaccine effectiveness, US$671 at 95% effectiveness); the average per capita WTP for household members was US$220 at 50% effectiveness and US$242 at 95% effectiveness. Although spouses reported that they would purchase the same total number of vaccines, and had essentially the same demand functions, at lower vaccine prices wives were significantly more likely than husbands to allocate vaccines to their daughters than to sons. CONCLUSIONS: Because wives are more likely to allocate vaccines to daughters, vaccination programs aimed at women and girls might have different outcomes than programs directed at males or at all potential adults without regard to sex.

Demand forecasting for preventive AIDS vaccines: economic and policy dimensions.

BACKGROUND: An AIDS vaccine could play a very significant role in reversing the HIV pandemic, saving millions of lives. For a vaccine to have such an impact, it must be widely available and adopted and taken up rapidly in the countries most affected. A demand-forecasting model provides a valuable tool that can guide R&D spending decisions and identify policy actions to help achieve these goals. OBJECTIVE: To identify the key determinants of vaccine demand, model global adoption and uptake dynamics, estimate potential demand and revenues associated with future preventive AIDS vaccines, and to conduct sensitivity analyses to assess the impact of each parameter on demand. METHODS: A discrete, deterministic, linear, predictive mathematical model based on stratified population averages with a 30-year time horizon was developed to assess scenarios of future demand. This forecasting model was used to explore the effects of vaccine characteristics and a variety of regulatory, political, financial and health service factors on future demand and revenues. The intervention modelled was a preventive AIDS vaccine (efficacy: 30-90%; duration of protection: 3-5 years; in a two-dose prime-boost combination). The main outcome measure was the number of complete courses of vaccine administered. RESULTS: The model suggests that demand for a preventive AIDS vaccine with a medium efficacy (50%) and duration of protection (3 years) would average 68 million courses annually over a 30-year period. Under different scenarios, demand would peak at 38-152 million courses annually. On the basis of tiered pricing across public and private markets ($US2-100 per dose), these levels of peak demand would translate into $US2.5-5.5 billion in peak annual sales revenues. Private markets and high-income countries account for small volumes but large shares of projected revenues, while low-income countries account for large volumes and more modest, but still significant, sales revenues. Vaccinations to 'catch-up' those who are missed or not eligible for routine annual programmes (whether adolescent or high-risk populations) would account for 20-35% of cumulative vaccination courses across all scenarios. Demand was found to be sensitive to vaccine efficacy, duration of protection and price. Efforts to expedite regulatory review processes, improve immunization infrastructure and reduce political constraints could increase demand for an AIDS vaccine by 40 million additional courses a year compared with the medium efficacy (baseline) vaccine forecast. CONCLUSIONS: Our model can provide vaccine developers with credible estimates of market potential for an AIDS vaccine, and with a tool that can be used to improve forecasts over time as AIDS vaccine science progresses. It can also help governments to identify and pursue those policies that could best strengthen demand and uptake of a safe and effective preventive AIDS vaccine.