221 results found
Fu H, Lin H-H, Hallett TB, et al., Explaining age disparities in tuberculosis burden in Taiwan: a modelling study., BMC Infectious Diseases, ISSN: 1471-2334
Thomas R, Skovdal M, Gallizzi M, et al., 2020, Improving risk perception and uptake of voluntary medical male circumcision with peer-education sessions and incentives, in Manicaland, East Zimbabwe: study protocol for a pilot randomised trial, Trials, Vol: 21, ISSN: 1745-6215
BackgroundVoluntary medical male circumcision (VMMC) is a key component of combination HIV-prevention programmes. Several high-HIV-prevalence countries in sub-Saharan Africa, including Zimbabwe, are looking to scale up VMMC activities. There is limited evidence on how a combination of social learning from peer education by a role model with different behavioural incentives influences demand for VMMC in such settings.Methods/DesignThis matched-cluster randomised controlled trial with 1740 participants will compare two behavioural incentives against a control with no intervention. In the intervention clusters, participants will participate in an education session delivered by a circumcised young male (“role model”) on the risks of HIV infection and the benefits from medical male circumcision. All participants will receive contributions towards transport costs to access medical male circumcision at participating clinics. Via blocked randomisation, in the intervention clusters participants will be randomly assigned to receive one of two types of incentives – fixed cash payment or lottery payment – both conditional on undergoing surgical VMMC. In two sites, a community-led intervention will also be implemented to address social obstacles and to increase support from peers, families and social structures. Baseline measures of endpoints will be gathered in surveys. Follow-up assessment at 6 months will include self-reported uptake of VMMC triangulated with clinic data.DiscussionThis is the first trial to pilot-test social learning to improve risk perception and self-efficacy and to address the fear of pain associated with VMMC and possible present-biased preferences with front-loaded compensations as well as fixed or lottery-based cash payments. This study will generate important knowledge to inform HIV-prevention policies about the effectiveness of behavioural interventions and incentives, which could be easily scaled-up.Trial registrationThis tria
Nayagam AS, Chan P, Zhao K, et al., Investment case for a comprehensive package of interventions against Hepatitis B in China; applied modelling to help national strategy planning, Clinical Infectious Diseases, ISSN: 1058-4838
Background:In2016,the first globalviralhepatitiselimination targetswere endorsed. Anestimated one-third of the world’schronic HBV infected population live in China and liver cancer is the sixth leading cause of mortality, but coverage of first line antiviral treatment was low. In 2015, China was one of the first countriesto initiate a consultative process for a renewed approach to viral hepatitis. We present the investment case for the scale-up of a comprehensive package of HBV interventions. Methods:Adynamic simulation modelof HBV was developedand used to simulate the Chinese HBV epidemic. We evaluated the impact, costs and return on investment of a comprehensive package of prevention and treatment interventions from a societal perspective, incorporating costs of management of end-stage liver disease and lost productivity costs. Results:Despitethe successes of historical vaccination scale-up since 1992, there will be a projected 60millionpeople still living with HBV in 2030 and 10 million HBV-related deaths, including 5.7millionHBV-related cancer deaths between 2015-2030. This could be reduced by 2.1million by highly active case-finding and optimal antiviral treatment regimens. The package of interventions is likely to have a positive return-on-investment to society, of 1.57US$ per US$ invested. Conclusions:Increases in HBV-related deaths for the next few decades pose a major public health threatin China. Active case-finding and access to optimal antiviral treatment is requiredto mitigate this risk. This investment case approachprovides a real-world example of howapplied modellingcansupportnational dialogue and inform policy planning.
Eaton JW, Brown T, Puckett R, et al., 2019, The estimation and projection package age-sex model and the r-hybrid model: new tools for estimating HIV incidence trends in sub-Saharan Africa., AIDS, Vol: 33, Pages: S235-S244, ISSN: 0269-9370
OBJECTIVES: Improve models for estimating HIV epidemic trends in sub-Saharan Africa (SSA). DESIGN: Mathematical epidemic model fit to national HIV survey and ANC sentinel surveillance (ANC-SS) data. METHODS: We modified EPP to incorporate age and sex stratification (EPP-ASM) to more accurately capture the shifting demographics of maturing HIV epidemics. Secondly, we developed a new functional form for the HIV transmission rate, termed 'r-hybrid', which combines a four-parameter logistic function for the initial epidemic growth, peak, and decline followed by a first-order random walk for recent trends after epidemic stabilization. We fitted the r-hybrid model along with previously developed r-spline and r-trend models to HIV prevalence data from household surveys and ANC-SS in 177 regions in 34 SSA countries. We used leave-one-out cross validation with household survey HIV prevalence to compare model predictions. RESULTS: The r-hybrid and r-spline models typically provided similar HIV prevalence trends, but sometimes qualitatively different assessments of recent incidence trends because of different structural assumptions about the HIV transmission rate. The r-hybrid model had the lowest average continuous ranked probability score, indicating the best model predictions. Coverage of 95% posterior predictive intervals was 91.5% for the r-hybrid model, versus 87.2 and 85.5% for r-spline and r-trend, respectively. CONCLUSION: The EPP-ASM and r-hybrid models improve consistency of EPP and Spectrum, improve the epidemiological assumptions underpinning recent HIV incidence estimates, and improve estimates and short-term projections of HIV prevalence trends. Countries that use general population survey and ANC-SS data to estimate HIV epidemic trends should consider using these tools.
Eaton J, Brown T, Puckett R, et al., 2019, The Estimation and Projection Package Age-Sex Model and the r-hybrid modelnew tools for estimating HIV incidence trends in sub-Saharan Africa, AIDS, Vol: 33, Pages: S235-S244, ISSN: 0269-9370
Objectives: Improve models for estimating HIV epidemic trends in sub-Saharan Africa (SSA).Design: Mathematical epidemic model fit to national HIV survey and ANC sentinel surveillance(ANC-SS) data.Methods: We modified EPP to incorporate age and sex stratification (EPP-ASM) to moreaccurately capture the shifting demographics of maturing HIV epidemics. Secondly, wedeveloped a new functional form, termed ‘r-hybrid’, for the HIV transmission rate whichcombines a four-parameter logistic function for the initial epidemic growth, peak, and declinefollowed by a first-order random walk for recent trends after epidemic stabilization. We fitted ther-hybrid model along with previously developed r-spline and r-trend models to HIV prevalencedata from household surveys and ANC-SS in 177 regions in 34 SSA countries. We used leaveone-out cross validation with household survey HIV prevalence to compare model predictions.Results: The r-hybrid and r-spline models typically provided similar HIV prevalence trends, butsometimes qualitatively different assessments of recent incidence trends due to differentstructural assumptions about the HIV transmission rate. The r-hybrid model had the lowestaverage continuous ranked probability score, indicating the best model predictions. Coverage of95% posterior predictive intervals was 91.5% for the r-hybrid model, versus 87.2% and 85.5%for r-spline and r-trend, respectively.Conclusions: The EPP-ASM and r-hybrid models improve consistency of EPP and Spectrum,improve the epidemiological assumptions underpinning recent HIV incidence estimates, andimprove estimates and short-term projections of HIV prevalence trends. Countries that usegeneral population survey and ANC-SS data to estimate HIV epidemic trends should considerusing these tools.
Thomas R, Skovdal M, Galizzi MM, et al., 2019, Improving risk perception and uptake of pre-exposure prophylaxis (PrEP) through interactive feedback-based counselling with and without community engagement in young women in Manicaland, East Zimbabwe: study protocol for a pilot randomized trial, Trials, Vol: 20, ISSN: 1745-6215
BackgroundHIV incidence in adolescent girls and young women remains high in sub-Saharan Africa. Progresstowards uptake of HIV prevention methods remains low. Studies of oral PrEP have shown that uptakeand adherence may be low due to low risk perception and ambivalence around using antiretroviralsfor prevention. No evidence exists on whether an interactive intervention aimed at adjusting riskperception and addressing the uncertainty around PrEP will improve uptake. This pilot research trialaims to provide an initial evaluation of the impact of an interactive digital tablet-based counsellingsession, correcting risk perception and addressing ambiguity around availability, usability andeffectiveness of PrEP.Methods/DesignThis is a matched-cluster randomised controlled trial which will compare an interactive tablet-basededucation intervention against a control with no intervention. The study will be implemented in eightsites. In each site, two matched clusters of villages will be created. One cluster will be randomlyallocated to intervention. In two sites a community engagement intervention will also be implementedto address social obstacles and to increase support from peers, families and social structures. 1,200HIV-negative young women 18-24 years, not on PrEP at baseline will be eligible. Baseline measures ofendpoints will be gathered in surveys. Follow-up assessment at six months will include bio-markers ofPrEP uptake and surveys.DiscussionThis will be the first randomized controlled trial to determine whether interactive feedbackcounselling leads to uptake of HIV prevention methods such as PrEP and reduces risky sexualbehaviour. If successful, policymakers could consider such an intervention in school-based educationcampaigns or as post- HIV-testing counselling for young people.Trial RegistrationThis trial has been registered on clinicaltrials.gov on 21/06/2018 (identifier: NCT03565575).https://clinicaltrials.gov/ct2/show/NCT03565575
Smit M, Perez-Guzman P, Mutai KK, et al., Mapping the current and future non-communicable disease burden in Kenya by HIV status: a modelling study, Clinical Infectious Diseases, ISSN: 1058-4838
Background:Then on-communicable disease (NCD) burden in Kenya is not well characterised, despite estimates needed to identify future health priorities. We aimto quantify current and future NCD burden in Kenya by HIV status. Methods: Original systematic reviews (SRs) and meta-analyses of prevalence/incidence of cardiovascular disease (CVD), chronic kidney disease, depression, diabetes, high total cholesterol, hypertension, human papillomavirus infection and related pre-cancerous stages in Kenya were carried out. An individual-based model was developed, simulating births, deaths, HIV-diseaseand treatment, aforementioned NCDs and cancers. The model was parameterised using SR, epidemiological national and regional surveillance data. NCD burden was quantified for 2018-2035 by HIV statusamongst adults. Findings: SRsidentified prevalence/incidence data for eachNCD, except ischemic heart disease. The model estimates that 51% of Kenyan adults currently suffer from ≥1 NCD, with a higher burden in People Living with HIV (PLHIV)compared to HIV-negative (62% versus 51%), driven by theirhigher age profile and partlyby HIV-related risk for NCDs. Hypertension and high total cholesterolarethe main NCD drivers(adult prevalence of 20·5% (5·3 million) and 9·0% (2·3 million)), with CVD and cancers the main causesof death. The burden is projectedto increase by 2035 (56% in HIV-negative; 71% in PLHIV), with population growth doublingthe number of people needing services (15·4 million to 28·1million)by 2035. Conclusions:NCD services will need to be expanded in Kenya. Guidelines in Kenya already support provision of these amongst both the general and HIV-positive population, however coverage remains low.
Hallett T, Hauck K, 2019, The Global Fund impact, The Lancet, Vol: 394, Pages: 1708-1709, ISSN: 0140-6736
Beacroft L, Smith JA, Hallett TB, 2019, What impact could DMPA use have had in South Africa and how might its continued use affect the future of the HIV epidemic?, Journal of the International AIDS Society, Vol: 22, Pages: 1-6, ISSN: 1758-2652
IntroductionSome studies suggest that use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase susceptibility to HIV infection. We aim to determine the influence that such an association could have had on the HIV epidemic in South Africa.MethodsWe simulate the heterosexual adult HIV epidemic in South Africa using a compartmental model stratified by age, behavioural risk group, sex, male circumcision status and contraceptive use. We model two possible scenarios: (1) The “With Effect” scenario assumes that DMPA increases susceptibility to HIV infection by 1.20‐fold (95% confidence interval 1.06 to 1.36) based on a combination of the results of a recent randomised controlled trial (ECHO trial) and a number of observational studies. (2) The “No Effect” scenario assumes that DMPA has no effect on HIV acquisition risk. We calculate the difference in HIV‐related outcomes between the With Effect and No Effect scenarios to determine the potential impact that DMPA use could have had on the HIV epidemic.ResultsA causal association between DMPA and HIV acquisition could have caused 430,000 (90% of model runs 160,000 to 960,000) excess HIV infections and 230,000 (90,000 to 470,000) AIDS deaths in South Africa from 1980 to 2017. These figures represent 4.3% (1.6% to 9.6%) and 6.9% (2.6% to 15.2%) of the total modelled estimates of HIV infections and AIDS deaths respectively in South Africa in that period. Of the additional infections, 36% (25% to 48%) would have occurred among men. If DMPA use continues at current levels, a potential causal association could cause an additional 130,000 (50,000 to 270,000) infections between 2018 and 2037. The excess infections would have required an additional 640,000 (190,000 to 1,660,000) years of ART from 1980 to 2017, and a further 2,870,000 (890,000 to 7,270,000) years of ART from 2018 to 2037.ConclusionsIf there is a causal association between DMPA use and HIV risk, it could have subs
Haacker M, Hallett T, Atun R, On discount rates for economic evaluations in global health, Health Policy and Planning, ISSN: 0268-1080
Choices on discount rates have important implications for the outcomes of economic evaluations of health interventions and policies. In global health, such evaluations typically apply a discount rate of 3 percent for health outcomes and costs, mirroring guidance developed for high‐income countries, notably the United States.The paper investigates the suitability of thes eguidelines for global health (i.e.,with a focus on low‐ and middle‐income countries), and seeks to identify best practice. Our analysis builds on an overview of the academic literature on discounting in health evaluations, existing academic or government‐related guidelines on discounting, are view on discount rates applied in economic evaluations in global health, and cross‐country macroeconomic data. The social discount rate generally applied in global health of 3 percent annually is in consistent with rates of economic growth experienced outside the most advanced economies. Forlow‐ and lower‐middle income countries, a discount rate of at least 5 percent is more appropriate, and one around 4 percent for upper‐middle income countries. Alternative approaches–e.g., motivated by the returns to alternative investments or by the cost of financing–could usefully be applied, dependent on policy context. The current practise could lead to systematic bias toward over‐valuing the future costs and health benefits of interventions. For health economic evaluations in global health, guidelines on discounting need to be adapted to take account of the different economic context of low‐ and middle‐income countries.
Stopard IJ, Hauck K, Hallett TB, 2019, The influence of constraints on the efficient allocation of resources for HIV prevention: authors' response, AIDS, Vol: 33, Pages: 1950-1951, ISSN: 0269-9370
Case K, Gomez G, Hallett T, 2019, The impact, cost and cost-effectiveness of oral pre-exposure prophylaxis in sub-Saharan Africa: a scoping review of modelling contributions and way forward, Journal of the International AIDS Society, Vol: 22, ISSN: 1758-2652
Introduction: Oral pre-exposure prophylaxis (PrEP) is a new form of HIV prevention being considered for inclusion in national prevention portfolios. Many mathematical modelling studies have been undertaken that speak to the impact, cost and cost-effectiveness of PrEP programmes. We assess the available evidence from mathematical modelling studies to inform programme planning and policy decision making for PrEP and further research directions.Methods: We conducted a scoping review of the published modelling literature. Articles published in English which modelled oral PrEP in sub-Saharan Africa, or non-specific settings with relevance to generalised HIV epidemic settings, were included. Data were extracted for the strategies of PrEP use modelled, and the impact, cost and cost-effectiveness of PrEP for each strategy. We define an algorithm to assess the quality and relevance of studies included, summarise the available evidence and identify the current gaps in modelling. Recommendations are generated for future modelling applications and data collection.Results and discussion: We reviewed 1,924 abstracts and included 44 studies spanning 2007 to 2017. Modelling has reported that PrEP can be a cost-effective addition to HIV prevention portfolios for some use cases, but also that it would not be cost-effective to fund PrEP before other prevention intervention are expanded. However, our assessment of the quality of the modelling indicates cost-effectiveness analyses failed to comply with standards of reporting for economic evaluations and the assessment of relevance highlighted that both key parameters and scenarios are now outdated. Current evidence gaps include modelling to inform service development using updated programmatic information and ex post modelling to evaluate and inform efficient deployment of resources in support of PrEP, especially among key populations, using direct evidence of cost, adherence and uptake patterns.Conclusions: Updated modelling which more
Cooke GS, Hallett TB, 2019, Pricing viral hepatitis as part of universal health coverage, The Lancet Global Health, Vol: 7, Pages: e1148-e1149, ISSN: 2214-109X
Moorhouse L, Schaefer R, Thomas R, et al., 2019, Application of the HIV prevention cascade to identify, develop,and evaluate interventions to improve use of prevention methods:Examples from a study in east Zimbabwe, Journal of the International AIDS Society, Vol: 22, Pages: 86-92, ISSN: 1758-2652
Introduction: The HIV prevention cascade could be used in developing interventions to strengthen implementation of efficacious HIV prevention methods but its practical utility needs to be demonstrated. We propose a standardised approach to using the cascade to guide identification and evaluation of interventions and demonstrate its feasibility through a project to develop interventions to improve use of HIV prevention methods by adolescent girls and young women (AGYW) and potential male partners in east Zimbabwe.Discussion: We propose a six-step approach to using a published generic HIV prevention cascade formulation to develop interventions to increase motivation to use, access to and effective use of an HIV prevention method. The six steps are: (1) measure the HIV prevention cascade for the chosen population and method; (2) identify gaps in the cascade; (3) identify explanatory factors (barriers) contributing to observed gaps; (4) review literature to identify relevant theoretical frameworks and interventions; (5) tailor interventions to the local context; and (6) implement and evaluate the interventions using the cascade steps and explanatory factors as outcome indicators in the evaluation design. In the Zimbabwe example, steps 1-5 aided development of four interventions to overcome barriers to effective use of PrEP in AGYW (15-24 years) and VMMC in male partners (15-29). For young men, prevention cascade analyses identified gaps in motivation and access (due to transport costs/lost income) as barriers to VMMC uptake, so an intervention was designed including financial incentives and an education session. For AGYW, gaps in motivation (particularly lack of risk perception) and access were identified as barriers to PrEP uptake: an interactive counselling game was developed addressing these barriers. A text messaging intervention was developed to improve adherence to PrEP among AGYW, addressing reasons underlying lack of effective PrEP use through improving the capa
Phillips AN, Cambiano V, Nakagawa F, et al., 2019, Cost-per-diagnosis as a metric for monitoring cost effectiveness of HIV testing programmes in low income settings in southern Africa: health economic and modelling analysis, Journal of the International AIDS Society, Vol: 22, Pages: 1-10, ISSN: 1758-2652
Introduction: As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost effective. To guide their HIV testing programmes,countries require appropriatemetrics that can be measured. The cost-per-diagnosisis potentially a useful metric. Methods:We simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of “core” testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) “core” testing as above plus “additional-testing”, for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than thosewithout HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosisand the incremental cost-effectiveness ratio(ICER) of the additional-testingpolicy. Discount rate 3%; costs in 2018 $US. Results:There was a strong graded relationship between the cost-per-diagnosisand the ICER. Overall, the ICERwas below $500 per-DALY-averted (the cost effectiveness threshold used in primary analysis) so long as thecost-per-diagnosiswas below $315. This thresholdcost-per-diagnosiswas similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restrictingto women, additional-testingdid not appear cost-effective even at acost-per-diagnosisof below $50, while restrictingto men additional-testingwas cost effective up to a cost-per-diagnosisof $585. Thethreshold cost for testing in men fell to $256 when the cost effectiveness threshold was $300instead of $5
Beacroft L, Hallett TB, 2019, The potential impact of a "curative intervention" for HIV: a modelling study., Global Health Research and Policy, Vol: 4, Pages: 1-8, ISSN: 2397-0642
Background: Efforts to develop an HIV "cure" (i.e., an intervention leading to durable ART-free remission or eradication of HIV infection) have become better resourced and coordinated in recent years. Given, however, the availability of other interventions for prevention and treatment of HIV disease, it is unclear whether, to what extent, and under which circumstances a curative intervention would have an impact in ending the AIDS epidemic and which characteristics of its implementation would be most important. We designed a range of analyses to investigate these unknowns. Methods: We used a deterministic, compartmental model of HIV infection in South Africa to estimate the impact of a curative intervention. We first examined how its impact would be affected by the state of the epidemic at the time that it is introduced, by the timing and pace of scale-up, and by various targeting strategies. We then investigated the impact of a curative intervention relative to its ability to maintain viral suppression. Findings: To the extent that other interventions have failed to control the epidemic, i.e., if incidence and AIDS deaths remain high, a curative intervention would result in a larger reduction in incidence. Earlier and faster scale-up allows for greater impact. We also found that a curative intervention would more efficiently reduce transmission if it is prioritised to those not able to obtain or remain on ART and to those aged 15-25 rather than older persons. On the other hand, an intervention that does not maintain viral suppression if the individual is exposed to re-infection could lead to an increase in HIV incidence. Conclusions: Our findings suggest that a curative intervention for HIV would have the greatest impact if the epidemic is not under control by 2030, particularly if the intervention is targeted to those who are more likely to transmit virus, and if it maintained durable viral suppression, even upon exposure to re-infection. These considera
Mangal TD, Pascom ARP, Vesga JF, et al., 2019, Estimating HIV incidence from surveillance data indicates a second wave of infections in Brazil, Epidemics, Vol: 27, Pages: 77-85, ISSN: 1755-4365
Emerging evidence suggests that HIV incidence rates in Brazil, particularly among men, may be rising. Here we use Brazil’s integrated health systems data to develop a mathematical model, reproducing the complex surveillance systems and providing estimates of HIV incidence, number of people living with HIV (PLHIV), reporting rates and ART initiation rates.An age-structured deterministic model with a flexible spline was used to describe the natural history of HIV along with reporting and treatment rates. Individual-level surveillance data for 1,077,295 cases (HIV/AIDS diagnoses, ART dispensations, CD4 counts and HIV/AIDS-related deaths) were used to calibrate the model using Bayesian inference.The results showed a second wave of infections occurring after 2001 and 56,000 (95% Credible Interval 43,000–71,000) new infections in 2015, 37,000 (95% CrI 28,000–54,000) infections in men and 16,000 (95% CrI 10,000–23,000) in women. The estimated number of PLHIV by end-2015 was 838,000 (95% CrI 675,000–1,083,000), with 80% (95% CrI 62–98%) of those individuals reported to the Ministry of Health. Women were more likely to be diagnosed and reported than men; 86.8% of infected women had been reported compared with 75.7% of men. Likewise, ART initiation rates for women were higher than those for men.The second wave contradicts previous estimates of HIV incidence trends in Brazil and there were persistent differences in the rates of accessing care between men and women. Nevertheless, the Brazilian HIV program has achieved high rates of detection and treatment, making considerable progress over the past ten years.
Stopard I, McGillen J, Hauck K, et al., 2019, The influence of constraints on the efficient allocation of resources for HIV prevention: a modelling study, AIDS, Vol: 33, Pages: 1241-1246, ISSN: 0269-9370
Objective: To investigate how ‘real-world’ constraints on the allocative and technical efficiency of HIV prevention programmes affect resource allocation and the number of infections averted.Design: Epidemiological modelling and economic analyses in Benin, South Africa and Tanzania.Methods: We simulated different HIV prevention programmes, and first determined the most efficient allocation of resources, in which the HIV prevention budget is shared between specific interventions, risk-groups and provinces to maximise the number of infections averted. We then identified the efficient allocation of resources and achievable impact given constraints to allocative efficiency: earmarking (provinces with budgets fund PrEP for low-risk women first), meeting treatment targets (provinces with budgets fund UTT first) and minimizing changes in the geographical distribution of funds. We modelled technical inefficiencies as a reduction in the coverage of PrEP or UTT, which were factored into the resource allocation process or took effect following the allocation. Each scenario was investigated over a range of budgets, such that the impact reaches its maximum.Results: The ‘earmarking’, ‘meeting targets’ and ‘minimizing change’ constraints reduce the potential impact of HIV prevention programmes, but at the higher budgets these constraints have little to no effect (approximately 35 billion US$ in Tanzania). Over-estimating technical efficiencies results in a loss of impact compared to what would be possible if technical efficiencies were known accurately.Conclusions: Failing to account for constraints on allocative and technical efficiency can result in the overestimation of the health gains possible, and for technical inefficiencies the allocation of an inefficient strategy.
Vesga JF, Hallett TB, Reid MJA, et al., 2019, Assessing tuberculosis control priorities in high-burden settings: a modelling approach, The Lancet Global Health, Vol: 7, Pages: e585-e595, ISSN: 2214-109X
Background:In the context of WHO's End TB strategy, there is a need to focus future control efforts on those interventions and innovations that would be most effective in accelerating declines in tuberculosis burden. Using a modelling approach to link the tuberculosis care cascade to transmission, we aimed to identify which improvements in the cascade would yield the greatest effect on incidence and mortality.Methods:We engaged with national tuberculosis programmes in three country settings (India, Kenya, and Moldova) as illustrative examples of settings with a large private sector (India), a high HIV burden (Kenya), and a high burden of multidrug resistance (Moldova). We collated WHO country burden estimates, routine surveillance data, and tuberculosis prevalence surveys from 2011 (for India) and 2016 (for Kenya). Linking the tuberculosis care cascade to tuberculosis transmission using a mathematical model with Bayesian melding in each setting, we examined which cascade shortfalls would have the greatest effect on incidence and mortality, and how the cascade could be used to monitor future control efforts.Findings:Modelling suggests that combined measures to strengthen the care cascade could reduce cumulative tuberculosis incidence by 38% (95% Bayesian credible intervals 27–43) in India, 31% (25–41) in Kenya, and 27% (17–41) in Moldova between 2018 and 2035. For both incidence and mortality, modelling suggests that the most important cascade losses are the proportion of patients visiting the private health-care sector in India, missed diagnosis in health-care settings in Kenya, and drug sensitivity testing in Moldova. In all settings, the most influential delay is the interval before a patient's first presentation for care. In future interventions, the proportion of individuals with tuberculosis who are on high-quality treatment could offer a more robust monitoring tool than routine notifications of tuberculosis.Interpretation:Linked to transmissi
Christian S, Anna B, Dobromir D, et al., 2019, Targeting and vaccine durability are key for population-level impact and cost-effectiveness of a pox-protein HIV vaccine tegimen in South Africa, Vaccine, Vol: 37, Pages: 2258-2267, ISSN: 0264-410X
BackgroundRV144 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.MethodsConsistent 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.ResultsOur 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).ConclusionsWhile 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 great
Heffernan A, Cooke G, Nayagam S, et al., 2019, Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model, Lancet, Vol: 393, Pages: 1319-1329, ISSN: 0140-6736
BackgroundThe revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met.MethodsWe developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions.FindingsBy 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0–15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000–670 000) from cirrhosis and liver cancer. A comprehensive p
Reid MJA, Arinaminpathy N, Bloom A, et al., 2019, Building a tuberculosis-free world: The Lancet Commission on tuberculosis, The Lancet, Vol: 393, Pages: 1331-1384, ISSN: 0140-6736
Borquez A, Guanira JV, Revill P, et al., 2019, The impact and cost-effectiveness of combined HIV prevention scenarios among transgender women sex-workers in Lima, Peru: A mathematical modelling study, Lancet Public Health, Vol: 4, Pages: e127-e136, ISSN: 2468-2667
BackgroundHIV incidence remains high among transgender women in Lima, Peru, most of whom report sex work. On the basis of a stakeholder analysis and health system capacity assessment, we designed a mathematical model to guide HIV programmatic planning among transgender women sex workers (TWSW) in Lima.MethodsUsing a deterministic compartmental model, we modelled HIV transmission among TWSW, their stable partners, and their clients to estimate the impact and cost-effectiveness of combinations of interventions compared with the standard of care on reducing HIV incidence over a 10-year period. We simulated HIV transmission accounting for differences in sexual positioning in anal intercourse and condom use by partner type and fitted the model to HIV surveillance data using Latin hypercube sampling. The interventions we considered were 15% relative increase in condom use with clients and 10% relative increase with stable partners; increase in antiretroviral treatment (ART) coverage at CD4 count lower than 500 cells per mm3 and greater than or equal to 500 cells per mm3; and 15% pre-exposure prophylaxis (PrEP) coverage using generic and branded formulations. We considered a basic scenario accounting for current limitations in the Peruvian HIV services and an enhanced scenario assuming achievement of the UNAIDS 90-90-90 targets and general improvements in HIV services. The 50 best fits according to log-likelihood were used to give the minimum and maximum values of intervention effect for each combination. We used disability-adjusted life-years (DALYs) to measure the negative health outcomes associated with HIV infection that could be averted through the interventions investigated and calculated incremental cost-effectiveness ratios to compare their cost-effectiveness.FindingsUnder the basic scenario, combining the four interventions of increasing condom use with clients and stable partners, extending ART to people with CD4 count greater than or equal to 500 cells per mm3
Mangal T, Meireles M, Pascom ARP, et al., 2019, Determinants of survival of people living with HIV/AIDS on antiretroviral therapy in Brazil 2006-2015, BMC Infectious Diseases, Vol: 19, ISSN: 1471-2334
BackgroundWe compared AIDS-related mortality rates in people living with HIV (PLHIV) starting antiretroviral therapy (ART) in Brazil during 2006–2015 and examined associated risk factors .MethodsData on ART use in PLHIV and AIDS mortality in Brazil was analysed with piecewise constant exponential models. Mortality rates and hazard ratios were estimated for 0–6, 6–12, 13–24, 25–36 and > 36 months of ART use and adjusted for region, age, sex, baseline CD4 cell count and calendar year of ART initiation. An additional analysis restricted to those with data on risk group was also performed.Results269,076 individuals were included in the analysis, 165,643 (62%) males and 103,433 (38%) females, with 1,783,305 person-years of follow-up time. 21,749 AIDS deaths were reported and 8898 deaths occurred in the first year of ART. The risk of death in the first six months decreased with early ART initiation; those starting treatment early with CD4 > 500 cells per μL had a hazard ratio of 0.06 (95% CI 0.05–0.07) compared with CD4 < 200 cells per μL. Older age, male sex, intravenous drug use and starting treatment in earlier calendar years were associated with higher mortality rates. People living in the North, Northeast and South of Brazil experienced significantly higher AIDS mortality rates than those in the Southeast (HR 1.44, [95% CI 1.35–1.54], 1.10 [1.05–1.16] and 1.22 [1.17–1.28] respectively).ConclusionsEarly treatment is likely to have contributed to the improved survival in PLHIV on ART, with the greatest benefits observed in women, younger age-groups and those living in the North.
Schaefer R, Gregson S, Fearon E, et al., 2019, HIV prevention cascades: A unifying framework to replicate the successes of treatment cascades, The Lancet HIV, Vol: 6, ISSN: 2405-4704
Many countries are off track to meet targets for reduction of new HIV infections. HIV prevention cascades have been proposed to assist in the implementation and monitoring of HIV prevention programmes by identifying gaps in the steps required for effective use of prevention methods, similar to HIV treatment cascades. However, absence of a unifying framework impedes widespread use of prevention cascades. Building on a series of consultations, we propose an HIV prevention cascade that consists of three key domains of motivation, access, and effective use in a priority population. This three step cascade can be used for routine monitoring and advocacy, particularly by attaching 90-90-90-style targets. Further characterisation of reasons for gaps across motivation, access, or effective use allows for a comprehensive framework that guides identification of relevant responses and platforms for interventions. Linkage of the prevention cascade, reasons for gaps, and interventions reconciles the different requirements of prevention cascades, providing a unifying framework.
Olney JJ, Eaton JW, Braitstein P, et al., 2019, Response to questionable assumptions mar modelling of Kenya home-based testing campaigns - a comment on "Optimal timing of HIV home-based counselling and testing rounds in Western Kenya" (Olney et al. 2018), Journal of the International AIDS Society, Vol: 22, ISSN: 1758-2652
Woods B, Rothery C, Anderson S-J, et al., 2018, Appraising the value of evidence generation activities: An HIV Modelling Study, BMJ Global Health, Vol: 3, ISSN: 2059-7908
Introduction: The generation of robust evidence has been emphasised as a priority for global health. Evidence generation spans a wide range of activities including clinical trials, surveillance programmes and health system performance measurement. As resources for healthcare and research are limited, the desirability of research expenditure should be assessed on the same basis as other healthcare resources, that is, the health gains from research must be expected to exceed the health opportunity costs imposed as funds are diverted to research rather than service provision.Methods: We developed a transmission and costing model to examine the impact of generating additional evidence to reduce uncertainties on the evolution of a generalised HIV epidemic in Zambia.Results: We demonstrate three important points. First, we can quantify the value of additional evidence in terms of the health gain it is expected to generate. Second, we can quantify the health opportunity cost imposed by research expenditure. Third, the value of evidence generation depends on the budgetary policies in place for managing HIV resources under uncertainty. Generating evidence to reduce uncertainty is particularly valuable when decision makers are required to strictly adhere to expenditure plans and when transfers of funds across geographies/programmes are restricted.Conclusion: Better evidence can lead to health improvements in the same way as direct delivery of healthcare. Quantitative appraisals of evidence generation activities are important and should reflect the impact of improved evidence on population health, evidence generation costs and budgetary policies in place.
Sarah-Jane A, Garnett G, Enstone J, et al., 2018, The importance of local epidemic conditions in monitoring progress towards HIV epidemic control in Kenya: a modelling study, Journal of the International AIDS Society, Vol: 21, ISSN: 1758-2652
IntroductionSetting and monitoring progress towards targets for HIV control is critical in ensuring responsive programmes. Here, we explore how to apply targets for reduction in HIV incidence to local settings and which indicators give the strongest signal of a change in incidence in the population and are therefore most important to monitor.MethodsWe use location‐specific HIV transmission models, tailored to the epidemics in the counties and major cities in Kenya, to project a wide range of plausible future epidemic trajectories through varying behaviours, treatment coverage and prevention interventions. We look at the change in incidence across modelled scenarios in each location between 2015 and 2030 to inform local target setting. We also simulate the measurement of a library of potential indicators and assess which are most strongly associated with a change in incidence.ResultsConsiderable variation was observed in the trajectory of the local epidemics under the plausible scenarios defined (only 10 of 48 locations saw a median reduction in incidence of greater than or equal to an 80% target by 2030). Indicators that provide strong signals in certain epidemic types may not perform consistently well in settings with different epidemiological features. Predicting changes in incidence is more challenging in advanced generalized epidemics compared to concentrated epidemics where changes in high‐risk sub‐populations track more closely to the population as a whole. Many indicators demonstrate only limited association with incidence (such as “condom use” or “pre‐exposure prophylaxis coverage”). This is because many other factors (low effectiveness, impact of other interventions, countervailing changes in risk behaviours, etc.) can confound the relationship between interventions and their ultimate long‐term impact, especially for an intervention with low expected coverage. The population prevalence of viral suppression shows the most consistent a
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.