Evaluating the potential impact and cost-effectiveness of dapivirine vaginal ring pre-exposure prophylaxis for HIV prevention.
ABSTRACT: BACKGROUND:Expanded HIV prevention options are needed to increase uptake of HIV prevention among women, especially in generalized epidemics. As the dapivirine vaginal ring moves forward through regulatory review and open-label extension studies, the potential public health impact and cost-effectiveness of this new prevention method are not fully known. We used mathematical modeling to explore the impact and cost-effectiveness of the ring in different implementation scenarios alongside scale-up of other HIV prevention interventions. Given the knowledge gaps about key factors influencing the ring's implementation, including potential uptake and delivery costs, we engaged in a stakeholder consultation process to elicit plausible parameter ranges and explored scenarios to identify the possible range of impact, cost, and cost-effectiveness. METHODS AND FINDINGS:We used the Goals model to simulate scenarios of oral and ring pre-exposure prophylaxis (PrEP) implementation among female sex workers and among other women ?21 years or >21 years with multiple male partners, in Kenya, South Africa, Uganda, and Zimbabwe. In these scenarios, we varied antiretroviral therapy (ART) coverage, dapivirine ring coverage and ring effectiveness (encompassing efficacy and adherence) by risk group. Following discussions with stakeholders, the maximum level of PrEP coverage (oral and/or ring) considered in each country was equal to modern contraception use minus condom use in the two age groups. We assessed results for 18 years, from 2018 to 2035. In South Africa, for example, the HIV infections averted by PrEP (ring plus oral PrEP) ranged from 310,000 under the highest-impact scenario (including ART held constant at 2017 levels, high ring coverage, and 85% ring effectiveness) to 55,000 under the lowest-impact scenario (including ART reaching the UNAIDS 90-90-90 targets by 2020, low ring coverage, and 30% ring effectiveness). This represented a range of 6.4% to 2.2% of new HIV infections averted. Given our assumptions, the addition of the ring results in 11% to 132% more impact than oral PrEP alone. The cost per HIV infection averted for the ring ranged from US$13,000 to US$121,000. CONCLUSIONS:This analysis offers a wide range of scenarios given the considerable uncertainty over ring uptake, consistency of use, and effectiveness, as well as HIV testing, prevention, and treatment use over the next two decades. This could help inform donors and implementers as they decide where to allocate resources in order to maximize the impact of the dapivirine ring in light of funding and implementation constraints. Better understanding of the cost and potential uptake of the intervention would improve our ability to estimate its cost-effectiveness and assess where it can have the most impact.
Project description:INTRODUCTION:A vaginal ring containing dapivirine is effective for HIV prevention as pre-exposure prophylaxis (PrEP). We evaluated the potential epidemiological impact and cost-effectiveness of dapivirine vaginal ring PrEP among 22- to 45-year-old women in KwaZulu-Natal, South Africa. METHODS:Using mathematical modelling, we studied dapivirine vaginal ring PrEP implementation, either unprioritized, or prioritized based on HIV incidence (≥3% per year), age (22 to 29 years) or female sex worker status, alongside the implementation of voluntary medical male circumcision and antiretroviral therapy scaled-up to UNAIDS Fast-Track targets. Outcomes over the intervention (2019 to 2030) and lifetime horizons included cumulative HIV infections, life-years lived, costs and cost-effectiveness. We assessed the incremental cost-effectiveness ratios against the revealed willingness to pay ($500) and the standard (2017 per capita gross domestic product; $6161) cost-effectiveness thresholds for South Africa. RESULTS:Compared to a reference scenario without PrEP, implementation of dapivirine vaginal ring PrEP, assuming 56% effectiveness and covering 50% of 22 to 29-year-old or high-incidence women, prevented 10% or 11% of infections by 2030 respectively. Equivalent, unprioritized coverage (30%) prevented fewer infections (7%), whereas 50% coverage of female sex workers had the least impact (4%). Drug resistance attributable to PrEP was modest (2% to 4% of people living with drug-resistant HIV). Over the lifetime horizon, dapivirine PrEP implementation among female sex workers was cost-saving, whereas incidence-based PrEP cost $1898 per life-year gained, relative to PrEP among female sex workers and $989 versus the reference scenario. In a scenario of 37% PrEP effectiveness, PrEP had less impact, but prioritization to female sex workers remained cost-saving. In uncertainty analysis, female sex worker PrEP was consistently cost-saving; and over the lifetime horizon, PrEP cost less than $6161 per life-year gained in over 99% of simulations, whereas incidence- and age-based PrEP cost below $500 per life-year gained in 61% and 49% of simulations respectively. PrEP adherence and efficacy, and the effectiveness of antiretroviral therapy for HIV prevention, were the principal drivers of uncertainty in the cost-effectiveness of PrEP. CONCLUSIONS:Dapivirine vaginal ring PrEP would be cost-saving in KwaZulu-Natal if prioritized to female sex workers. PrEP's impact on HIV prevention would be increased, with potential affordability, if prioritized to women by age or incidence.
Project description:HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations.We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a "conditional efficacy" parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036-US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained.A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary.
Project description:Pre-exposure prophylaxis (PrEP) is a promising new HIV prevention method, especially for women. An urgent demand for implementation of PrEP is expected at the moment efficacy has been demonstrated in clinical trials. We explored the long-term impact of PrEP on HIV transmission in different HIV epidemics.We used a mathematical model that distinguishes the general population, sex workers and their clients. PrEP scenarios varying in effectiveness, coverage and target group were modeled in the epidemiological settings of Botswana, Nyanza Province in Kenya, and Southern India. We also studied the effect of condom addition or condom substitution during PrEP use. Main outcome was number of HIV infections averted over ten years of PrEP use. PrEP strategies with high effectiveness and high coverage can have a substantial impact in African settings. In Southern India, by contrast, the number of averted HIV infections in different PrEP scenarios would be much lower. The impact of PrEP may be strongly diminished or even reversed by behavioral disinhibition, especially in scenarios with low coverage and low effectiveness. However, additional condom use during low coverage and low effective PrEP doubled the amount of averted HIV infections.The public health impact of PrEP can be substantial. However, this impact may be diminished, or even reversed, by changes in risk behavior. Implementation of PrEP strategies should therefore come on top of current condom campaigns, not as a substitution.
Project description:INTRODUCTION:Oral pre-exposure prophylaxis (PrEP) provision is a priority intervention for high HIV prevalence settings and populations at substantial risk of HIV acquisition. This mathematical modelling analysis estimated the impact, cost and cost-effectiveness of scaling up oral PrEP in 13 countries. METHODS:We projected the impact and cost-effectiveness of oral PrEP between 2018 and 2030 using a combination of the Incidence Patterns Model and the Goals model. We created four PrEP rollout scenarios involving three priority populations-female sex workers (FSWs), serodiscordant couples (SDCs) and adolescent girls and young women (AGYW)-both with and without geographic prioritization. We applied the model to 13 countries (Eswatini, Ethiopia, Haiti, Kenya, Lesotho, Mozambique, Namibia, Nigeria, Tanzania, Uganda, Zambia and Zimbabwe). The base case assumed achievement of the Joint United Nations Programme on HIV/AIDS 90-90-90 antiretroviral therapy targets, 90% male circumcision coverage by 2020 and 90% efficacy and adherence levels for oral PrEP. RESULTS:In the scenarios we examined, oral PrEP averted 3% to 8% of HIV infections across the 13 countries between 2018 and 2030. For all but three countries, more than 50% of the HIV infections averted by oral PrEP in the scenarios we examined could be obtained by rollout to FSWs and SDCs alone. For several countries, expanding oral PrEP to include medium-risk AGYW in all regions greatly increased the impact. The efficiency and impact benefits of geographic prioritization of rollout to AGYW varied across countries. Variations in cost-effectiveness across countries reflected differences in HIV incidence and expected variations in unit cost. For most countries, rolling out oral PrEP to FSWs, SDCs and geographically prioritized AGYW was not projected to have a substantial impact on the supply chain for antiretroviral drugs. CONCLUSIONS:These modelling results can inform prioritization, target-setting and other decisions related to oral PrEP scale-up within combination prevention programmes. We caution against extensive use given limitations in cost data and implementation approaches. This analysis highlights some of the immediate challenges facing countries-for example, trade-offs between overall impact and cost-effectiveness-and emphasizes the need to improve data availability and risk assessment tools to help countries make informed decisions.
Project description:Risk of HIV infection is high in Chinese MSM, with an annual HIV incidence ranging from 3.41 to 13.7/100 person-years. Tenofovir-based PrEP is effective in preventing HIV transmission in MSM. This study evaluates the epidemiological impact and cost-effectiveness of implementing PrEP in Chinese MSM over the next two decades. A compartmental model for HIV was used to forecast the impact of PrEP on number of infections, deaths, and disability-adjusted life years (DALY) averted. We also provide an estimate of the incremental cost-effectiveness ratio (ICER) and the cost per DALY averted of the intervention. Without PrEP, there will be 1.1-3.0 million new infections and 0.7-2.3 million HIV-related deaths in the next two decades. Moderate PrEP coverage (50%) would prevent 0.17-0.32 million new HIV infections. At Truvada's current price in China, daily oral PrEP costs $46,813-52,008 per DALY averted and is not cost-effective; on-demand Truvada reduces ICER to $25,057-27,838 per DALY averted, marginally cost-effective; daily generic tenofovir-based regimens further reduce ICER to $3675-8963, wholly cost-effective. The cost of daily oral Truvada PrEP regimen would need to be reduced by half to achieve cost-effectiveness and realize the public health good of preventing hundreds of thousands of HIV infections among MSM in China.
Project description:INTRODUCTION:In 2014, the Government of Thailand recommended pre-exposure prophylaxis (PrEP) as an additional HIV prevention programme within Thailand's National Guidelines on HIV/AIDS Treatment Prevention. However, to date implementation and uptake of PrEP programmes have been limited, and evidence on the costs and the epidemiological and economic impact is not available. METHODS:We estimated the costs associated with PrEP provision among men having sex with men (MSM) participating in a facility-based, prospective observational cohort study: the Test, Treat and Prevent HIV Programme in Thailand. We created a suite of scenarios to estimate the cost-effectiveness of PrEP and sensitivity of the results to the model input parameters, including PrEP programme effectiveness, PrEP uptake among high-risk and low-risk MSM, baseline and future antiretroviral therapy (ART) coverage, condom use, unit cost of delivering PrEP, and the discount rate. RESULTS:Drug costs accounted for 82.5% of the total cost of providing PrEP, followed by lab testing (8.2%) and personnel costs (7.8%). The estimated costs of providing the PrEP package in accordance with the national recommendation ranges from US$223 to US$311 per person per year. Based on our modelling results, we estimate that PrEP would be cost-effective when provided to either high-risk or all MSM. However, we found that the programme would be approximately 32% more cost-effective if offered to high-risk MSM than it would be if offered to all MSM, with an incremental cost-effectiveness ratio of US$4,836 per disability-adjusted life years (DALY) averted and US$7,089 per DALY averted respectively. Cost-effectiveness acceptability curves demonstrate that 80% of scenarios would be cost-effective when PrEP is provided solely to higher-risk MSM. CONCLUSION:We provide the first estimates on cost and cost-effectiveness of PrEP in the Asia-Pacific region, and offer insights on how to deliver PrEP in combination with ART. While the high drug cost poses a budgeting challenge, incorporating PrEP delivery into an existing ART programme could be a cost-effective strategy to prevent HIV infections among MSM in Thailand.
Project description:Background:The total population health benefits and costs of HIV preexposure prophylaxis (PrEP) for people who inject drugs (PWID) in the United States are unclear. Objective:To evaluate the cost-effectiveness and optimal delivery conditions of PrEP for PWID. Design:Empirically calibrated dynamic compartmental model. Data Sources:Published literature and expert opinion. Target Population:Adult U.S. PWID. Time Horizon:20 years and lifetime. Intervention:PrEP alone, PrEP with frequent screening (PrEP+screen), and PrEP+screen with enhanced provision of antiretroviral therapy (ART) for individuals who become infected (PrEP+screen+ART). All scenarios are considered at 25% coverage. Outcome Measures:Infections averted, deaths averted, change in HIV prevalence, discounted costs (in 2015 U.S. dollars), discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Results of Base-Case Analysis:PrEP+screen+ART dominates other strategies, averting 26 700 infections and reducing HIV prevalence among PWID by 14% compared with the status quo. Achieving these benefits costs $253 000 per QALY gained. At current drug prices, total expenditures for PrEP+screen+ART could be as high as $44 billion over 20 years. Results of Sensitivity Analysis:Cost-effectiveness of the intervention is linear in the annual cost of PrEP and is dependent on PrEP drug adherence, individual transmission risks, and community HIV prevalence. Limitation:Data on risk stratification and achievable PrEP efficacy levels for U.S. PWID are limited. Conclusion:PrEP with frequent screening and prompt treatment for those who become infected can reduce HIV burden among PWID and provide health benefits for the entire U.S. population, but, at current drug prices, it remains an expensive intervention both in absolute terms and in cost per QALY gained. Primary Funding Source:National Institute on Drug Abuse.
Project description:BACKGROUND: Mathematical modelers have given little attention to the question of how pre-exposure prophylaxis (PrEP) may impact on a generalized national HIV epidemic and its cost-effectiveness, in the context of control strategies such as condom use promotion and expanding ART programs. METHODOLOGY/PRINCIPAL FINDINGS: We use an age- and gender-structured model of the generalized HIV epidemic in South Africa to investigate the potential impact of PrEP in averting new infections. The model utilizes age-structured mortality, fertility, partnership and condom use data to model the spread of HIV and the shift of peak prevalence to older age groups. The model shows that universal PrEP coverage would have to be impractically high to have a significant effect on incidence reduction while ART coverage expands. PrEP targeted to 15-35-year-old women would avert 10%-25% (resp. 13%-28%) of infections in this group and 5%-12% (resp. 7%-16%) of all infections in the period 2014-2025 if baseline incidence is 0.5% per year at 2025 (resp. 0.8% per year at 2025). The cost would be $12,500-$20,000 per infection averted, depending on the level of ART coverage and baseline incidence. An optimistic scenario of 30%-60% PrEP coverage, efficacy of at least 90%, no behavior change among PrEP users and ART coverage less than three times its 2010 levels is required to achieve this result. Targeting PrEP to 25-35-year-old women (at highest risk of infection) improves impact and cost-effectiveness marginally. Relatively low levels of condom substitution (e.g., 30%) do not nullify the efficacy of PrEP, but reduces cost-effectiveness by 35%-40%. CONCLUSIONS/SIGNIFICANCE: PrEP can avert as many as 30% of new infections in targeted age groups of women at highest risk of infection. The cost-effectiveness of PrEP relative to ART decreases rapidly as ART coverage increases beyond three times its coverage in 2010, after which the ART program would provide coverage to more than 65% of HIV(+) individuals. To have a high relative cost-effective impact on reducing infections in generalized epidemics, PrEP must utilize a window of opportunity until ART has been scaled up beyond this level.
Project description:Clinical effectiveness of pre-exposure prophylaxis (PrEP) for preventing HIV acquisition in men who have sex with men (MSM) at high HIV risk is established. A static decision analytical model was constructed to inform policy prioritisation in England around cost-effectiveness and budgetary impact of a PrEP programme covering 5,000 MSM during an initial high-risk period. National genitourinary medicine clinic surveillance data informed key HIV risk assumptions. Pragmatic large-scale implementation scenarios were explored. At 86% effectiveness, PrEP given to 5,000 MSM at 3.3 per 100 person-years annual HIV incidence, assuming risk compensation (20% HIV incidence increase), averted 118 HIV infections over remaining lifetimes and was cost saving. Lower effectiveness (64%) gave an incremental cost-effectiveness ratio of?+?GBP 23,500 (EUR 32,000) per quality-adjusted life year (QALY) gained. Investment of GBP 26.9 million (EUR 36.6 million) in year-1 breaks even anywhere from year-23 (86% effectiveness) to year-33 (64% effectiveness). PrEP cost-effectiveness was highly sensitive to year-1 HIV incidence, PrEP adherence/effectiveness, and antiretroviral drug costs. There is much uncertainty around HIV incidence in those given PrEP and adherence/effectiveness, especially under programme scale-up. Substantially reduced PrEP drug costs are needed to give the necessary assurance of cost-effectiveness, and for an affordable public health programme of sufficient size.
Project description:<h4>Introduction</h4>Once-daily tenofovir/emtricitabine-based pre-exposure prophylaxis (PrEP) can reduce HIV acquisition in men who have sex with men (MSM), by 44% in the iPrEx trial, and reaching up to 99% with high adherence. We examined the potential population-level impact and cost-effectiveness of different PrEP implementation strategies.<h4>Methods</h4>We developed a dynamic, stochastic compartmental model of HIV transmission among the estimated 57,400 MSM in Toronto, Canada. Parameterization was performed using local epidemiologic data. Strategies examined included (1) uniform PrEP delivery versus targeting the highest risk decile of MSM (with varying coverage proportions); (2) increasing PrEP efficacy as a surrogate of adherence (44% to 99%); and (3) varying HIV test frequency (once monthly to once yearly). Outcomes included HIV infections averted and the incremental cost ($CAD) per incremental quality-adjusted-life-year (QALY) gained over 20 years.<h4>Results</h4>Use of PrEP among all HIV-uninfected MSM at 25, 50, 75 and 100% coverage prevented 1970, 3427, 4317, and 4581 infections, respectively, with cost/QALY increasing from $500,000 to $800,000 CAD. Targeted PrEP for the highest risk MSM at 25, 50, 75 and 100% coverage prevented 1166, 2154, 2816, and 3012 infections, respectively, with cost/QALY ranging from $35,000 to $70,000 CAD. Maximizing PrEP efficacy, in a scenario of 25% coverage of high-risk MSM with PrEP, prevented 1540 infections with a cost/QALY of $15,000 CAD. HIV testing alone (Q3 months) averted 898 of infections with a cost savings of $4,000 CAD per QALY.<h4>Conclusions</h4>The optimal implementation strategy for PrEP over the next 20 years at this urban centre is to target high-risk MSM and to maximize efficacy by supporting PrEP adherence. A large health benefit of PrEP implementation could come from engaging undiagnosed HIV-infected individuals into care.