Imperial College London

ProfessorTimothyHallett

Faculty of MedicineSchool of Public Health

Professor of Global Health
 
 
 
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Contact

 

+44 (0)20 7594 1150timothy.hallett

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

209 results found

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

Journal article

Case K, Gomez G, Hallett T, 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, 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

Journal article

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.

Journal article

Cooke GS, Hallett TB, 2019, Pricing viral hepatitis as part of universal health coverage, The Lancet Global Health, ISSN: 2214-109X

Journal article

Moorhouse L, Schaefer R, Thomas R, Nyamukapa C, Skovdal M, Hallett T, Gregson Set 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

Journal article

Phillips AN, Cambiano V, Nakagawa F, Bansi-Matharu L, Wilson D, Jani I, Apollo T, Sculpher M, Hallett T, Kerr C, van Oosterhout JJ, Eaton J, Estill J, Williams B, Doi N, Cowan F, Keiser O, Ford D, Hatzold K, Barnabas R, Ayles H, Meyer-Rath G, Nelson L, Johnson CC, Baggaley R, Fakoya A, Jahn A, Revill Pet al., 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, 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

Journal article

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

Journal article

Stopard I, McGillen J, Hauck K, Hallett TBet 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.

Journal article

Mangal TD, Pascom ARP, Vesga JF, Meireles MV, Benzaken AS, Hallett TBet 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.

Journal article

Christian S, Anna B, Dobromir D, Blythe A, Paul R, Hallett T, Andrew P, Linda-Gail B, Helen R, Glenda Get 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

Journal article

Heffernan A, Cooke G, Nayagam S, Hallett TB, Thursz Met 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

Journal article

Reid MJA, Arinaminpathy N, Bloom A, Bloom BR, Boehme C, Chaisson R, Chin DP, Churchyard G, Cox H, Ditiu L, Dybul M, Farrar J, Fauci AS, Fekadu E, Fujiwara PI, Hallett TB, Hanson CL, Harrington M, Herbert N, Hopewell PC, Ikeda C, Jamison DT, Khan AJ, Koek I, Krishnan N, Motsoaledi A, Pai M, Raviglione MC, Sharman A, Small PM, Swaminathan S, Temesgen Z, Vassall A, Venkatesan N, van Weezenbeek K, Yamey G, Agins BD, Alexandru S, Andrews JR, Beyeler N, Bivol S, Brigden G, Cattamanchi A, Cazabon D, Crudu V, Daftary A, Dewan P, Doepel LK, Eisinger RW, Fan V, Fewer S, Furin J, Goldhaber-Fiebert JD, Gomez GB, Graham SM, Gupta D, Kamene M, Khaparde S, Mailu EW, Masini EO, McHugh L, Mitchell E, Moon S, Osberg M, Pande T, Prince L, Rade K, Rao R, Remme M, Seddon JA, Selwyn C, Shete P, Sachdeva KS, Stallworthy G, Vesga JF, Vilc V, Goosby EPet al., 2019, Building a tuberculosis-free world: The Lancet Commission on tuberculosis, The Lancet, Vol: 393, Pages: 1331-1384, ISSN: 0140-6736

Journal article

Vesga JF, Hallett TB, Reid MJA, Sachdeva KS, Rao R, Khaparde S, Dave P, Rade K, Kamene M, Omesa E, Masini E, Omale N, Onyango E, Owiti P, Karanja M, Kiplimo R, Alexandru S, Vilc V, Crudu V, Bivol S, Celan C, Arinaminpathy Net al., 2019, Assessing tuberculosis control priorities in high-burden settings: a modelling approach, The Lancet Global Health, ISSN: 2214-109X

BackgroundIn 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.MethodsWe 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.FindingsModelling 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.InterpretationLinked to transmission

Journal article

Borquez A, Guanira JV, Revill P, Caballero P, Silva-Santisteban A, Kelly S, Salazar X, Bracamonte P, Minaya P, Hallett T, Cáceres CFet 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

Journal article

Ghys PD, Over M, Hallett TB, Mahy M, Godfrey-Faussett Pet al., 2019, Metrics and benchmarks for HIV transition, LANCET HIV, Vol: 6, Pages: E150-E150, ISSN: 2352-3018

Journal article

Mangal T, Meireles M, Pascom ARP, Coelho RDA, Benzaken AS, Hallett Tet 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.

Journal article

Schaefer R, Gregson S, Fearon E, Hensen B, Hallett T, Hargreaves JRet 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.

Journal article

Woods B, Rothery C, Anderson S-J, Eaton JW, Revill P, Hallett TB, Claxton Ket 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.

Journal article

Sarah-Jane A, Garnett G, Enstone J, Hallett Tet 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

Journal article

Ghys PD, Williams BG, Over M, Hallett TB, Godfrey-Faussett Pet al., 2018, Epidemiological metrics and benchmarks for a transition in the HIV epidemic, PLoS Medicine, Vol: 15, ISSN: 1549-1277

Peter Godfrey-Faussett and colleagues present six epidemiological metrics for tracking progress in reducing the public health threat of HIV.

Journal article

Fu H, Lin H-H, Hallett TB, Arinaminpathy Net al., 2018, Modelling the effect of discontinuing universal Bacillus Calmette-Guérin vaccination in an intermediate tuberculosis burden setting, Vaccine, Vol: 36, Pages: 5902-5909, ISSN: 0264-410X

BackgroundBacillus Calmette-Guérin (BCG) vaccination is a widely-used public health intervention for tuberculosis (TB) control. In Taiwan, like other intermediate TB burden settings, steadily declining TB incidence raises important questions on whether universal BCG vaccination should be discontinued. Recent surveys on adverse events following immunisation, such as BCG-induced osteomyelitis/osteitis, also suggest a need to re-evaluate the vaccination programme.MethodsWe developed an age-structured transmission dynamic model, calibrated to population demography and age-specific TB notification rates in Taiwan. We adopted ‘weak-protection’ and ‘strong-protection’ scenarios, representing a range of characteristics including the duration of BCG protection and vaccine efficacies against TB infection and progression. We estimated averted disability-adjusted life years (DALYs) and incremental costs over 10 years after discontinuing universal BCG vaccination in 2018, 2035, and 2050. We also examined the potential impact of ‘surveillance-guided’ discontinuation, triggered once notification rates fall to a given threshold.ResultsIn the weak-protection scenario, discontinuing BCG would result in 2.8 (95% uncertainty range: 2.3, 3.1) additional notified TB cases and −4.1 (−7.7, 0.8) net averted DALYs over 2018–2027. In the strong-protection scenario, 82.9 (72.6, 91.6) additional cases and −402.7 (−506.6, −301.2) averted DALYs would be reported, suggesting a robustly negative health impact. However, in this vaccine scenario, there could be an overall health benefit if BCG is discontinued once TB notification falls below 5 per 100,000 population. The most influential vaccine characteristic for the net health impact is the vaccine efficacy against progression to pulmonary TB. In financial terms, the eliminated cost of the vaccination programme substantially outweighed the incremental cost for TB treatme

Journal article

McGillen JB, Stover J, Klein DJ, Xaba S, Ncube G, Mhangara M, Chipendo GN, Taramusi I, Beacroft L, Hallett TB, Odawo P, Manzou R, Korenromp ELet al., 2018, The emerging health impact of voluntary medical male circumcision in Zimbabwe: An evaluation using three epidemiological models, PLoS ONE, Vol: 13, ISSN: 1932-6203

BackgroundZimbabwe adopted voluntary medical male circumcision (VMMC) as a priority HIV prevention strategy in 2007 and began implementation in 2009. We evaluated the costs and impact of this VMMC program to date and in future.MethodsThree mathematical models describing Zimbabwe’s HIV epidemic and program evolution were calibrated to household survey data on prevalence and risk behaviors, with circumcision coverage calibrated to program-reported VMMCs. We compared trends in new infections and costs to a counterfactual without VMMC. Input assumptions were agreed in workshops with national stakeholders in 2015 and 2017.ResultsThe VMMC program averted 2,600–12,200 infections (among men and women combined) by the end of 2016. This impact will grow as circumcised men are protected lifelong, and onward dynamic transmission effects, which protect women via reduced incidence and prevalence in their male partners, increase over time. If other prevention interventions remain at 2016 coverages, the VMMCs already performed will avert 24,400–69,800 infections (2.3–5% of all new infections) through 2030. If coverage targets are achieved by 2021 and maintained, the program will avert 108,000–171,000 infections (10–13% of all new infections) by 2030, costing $2,100–3,250 per infection averted relative to no VMMC. Annual savings from averted treatment needs will outweigh VMMC maintenance costs once coverage targets are reached. If Zimbabwe also achieves ambitious UNAIDS targets for scaling up treatment and prevention efforts, VMMC will reduce the HIV incidence remaining at 2030 by one-third, critically contributing to the UNAIDS goal of 90% incidence reduction.ConclusionsVMMC can substantially impact Zimbabwe’s HIV epidemic in the coming years; this investment will save costs in the longer term.

Journal article

Phillips A, Cambiano V, Bansi-Matharu L, Nakagawa F, Wilson D, Jani I, Apollo T, Sculpher M, Hallett T, Kerr C, van Oosterhout J, Eaton J, Estill J, Williams B, Doi N, Cowan F, Keiser O, Ford D, Hatzold K, Barnabas R, Ayles H, Meyer-Rath G, Nelson L, Johnson C, Baggaley R, Fakoya A, Jahn A, Revill Pet al., 2018, Cost-of-testing-per-new-HIV-diagnosis as a metric for monitoring cost-effectiveness of testing programmes in low income settings in Southern Africa: health economic modelling analysis, Publisher: JOHN WILEY & SONS LTD, Pages: 27-28

Conference paper

Olney JJ, Eaton J, Braitstein P, Hogan J, Hallett Tet al., 2018, Optimal timing of HIV home-based counselling and testing rounds in Western Kenya, Journal of the International AIDS Society, Vol: 21, ISSN: 1758-2652

Introduction:Weaknesses in care programmes providing anti‐retroviral therapy (ART) persist and are often instigated by late HIV diagnosis and poor linkage to care. We investigated the potential for a home‐based counselling and testing (HBCT) campaign to be improved through the optimal timing and enhancement of testing rounds to generate greater health outcomes at minimum cost.Methods:Using a mathematical model of HIV care calibrated to longitudinal data from The Academic Model Providing Access To Healthcare (AMPATH) in Kenya, we simulated HBCT campaigns between 2016 and 2036, assessing the impact and total cost of care for each, for a further 20 years.Results:We find that simulating five equally spaced rounds averts 1.53 million disability‐adjusted life‐years (DALYs) at a cost of $1617 million. By altering the timing of HBCT rounds, a four‐round campaign can produce greater impact for lower cost. With “front‐loaded” rounds, the cost per DALY averted is reduced by 12% as fewer rounds are required ($937 vs. $1060). Furthermore, improvements to HBCT coverage and linkage to care avert over two million DALYs at a cost per DALY averted of $621 (41% less than the reference scenario).Conclusions:Countries implementing HBCT can reduce costs by optimally timing rounds and generate greater health outcomes through improving linkage, coverage, and retention. Tailoring HBCT campaigns to individual settings can enhance patient outcomes for minimal cost.

Journal article

Heffernan A, Hallett T, Thursz M, Cooke G, Nayagam Set al., 2018, Global scale-up of hepatitis C interventions will reduce burden but not eliminate the disease, 16th International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD), Publisher: WILEY, Pages: 26-26, ISSN: 1352-0504

Conference paper

Meyer-Rath G, McGillen JB, Cuadros DF, Hallett TB, Bhatt S, Wabiri N, Tanser F, Rehle Tet al., 2018, Targeting the right interventions to the right people and places: the role of geospatial analysis in HIV program planning, AIDS, Vol: 32, Pages: 957-963, ISSN: 0269-9370

Journal article

Hecht R, Hiebert L, Spearman WC, Sonderup MW, Guthrie T, Hallett TB, Nayagam S, Razavi H, Soe-Lin S, Vilakazi-Nhlapo K, Pillay Y, Resch Set al., 2018, The investment case for hepatitis B and C in South Africa: adaptation and innovation in policy analysis for disease program scale-up, Health Policy and Planning, Vol: 33, Pages: 528-538, ISSN: 1460-2237

Even though WHO has approved global goals for hepatitis elimination, most countries have yet to establish programs for hepatitis B and C, which account for 320 million infections and over a million deaths annually. One reason for this slow response is the paucity of robust, compelling analyses showing that national HBV/HCV programs could have a significant impact on these epidemics and save lives in a cost-effective, affordable manner. In this context, our team used an investment case approach to develop a national hepatitis action plan for South Africa, grounded in a process of intensive engagement of local stakeholders. Costs were estimated for each activity using an ingredients-based, bottom-up costing tool designed by the authors. The health impact and cost-effectiveness of the Action Plan were assessed by simulating its four priority interventions (HBV birth dose vaccination, PMTCT, HBV treatment and HCV treatment) using previously developed models calibrated to South Africa's demographic and epidemic profile. The Action Plan is estimated to require ZAR3.8 billion (US$294 million) over 2017-2021, about 0.5% of projected government health spending. Treatment scale-up over the initial 5-year period would avert 13 000 HBV-related and 7000 HCV-related deaths. If scale up continues beyond 2021 in line with WHO goals, more than 670 000 new infections, 200 000 HBV-related deaths, and 30 000 HCV-related deaths could be averted. The incremental cost-effectiveness of the Action Plan is estimated at $3310 per DALY averted, less than the benchmark of half of per capita GDP. Our analysis suggests that the proposed scale-up can be accommodated within South Africa's fiscal space and represents good use of scarce resources. Discussions are ongoing in South Africa on the allocation of budget to hepatitis. Our work illustrates the value and feasibility of using an investment case approach to assess the costs and relative priority of scaling up HBV/HCV service

Journal article

Smit M, Olney J, Ford NP, Vitoria M, Gregson S, Vassall A, Hallett TBet al., 2018, The growing burden of non-communicable disease among persons living with HIV in Zimbabwe, AIDS, Vol: 32, Pages: 773-782, ISSN: 0269-9370

Objectives:We aim to characterize the future noncommunicable disease (NCD)burden in Zimbabwe to identify future health system priorities.Methods:We developed an individual-based multidisease model for Zimbabwe,simulating births, deaths, infection with HIV and progression and key NCD [asthma,chronic kidney disease (CKD), depression, diabetes, hypertension, stroke, breast,cervical, colorectal, liver, oesophageal, prostate and all other cancers]. The modelwas parameterized using national and regional surveillance and epidemiological data.Demographic and NCD burden projections were generated for 2015 to 2035.Results:The model predicts that mean age of PLHIV will increase from 31 to 45 yearsbetween 2015 and 2035 (compared with 20 –26 in uninfected individuals). Conse-quently, the proportion suffering from at least one key NCD in 2035 will increase by26% in PLHIV and 6% in uninfected. Adult PLHIV will be twice as likely to suffer from atleast one key NCD in 2035 compared with uninfected adults; with 15.2% of all keyNCDs diagnosed in adult PLHIV, whereas contributing only 5% of the Zimbabweanpopulation. The most prevalent NCDs will be hypertension, CKD, depression andcancers. This demographic and disease shift in PLHIV is mainly because of reductions inincidence and the success of ART scale-up leading to longer life expectancy, and to alesser extent, the cumulative exposure to HIV and ART.Conclusion:NCD services will need to be expanded in Zimbabwe. They will need tobe integrated into HIV care programmes, although the growing NCD burden amongstuninfected individuals presenting opportunities for additional services developedwithin HIV care to benefit HIV-negative persons.

Journal article

Anderson S, Ghys PD, Ombam R, Hallett TBet al., 2018, Frontloading HIV financing maximises the achievable impact of HIV prevention, Journal of the International AIDS Society, Vol: 21, ISSN: 1758-2652

Introduction:Due to the nature of funding, national planners and international donors typically balance budgets over short time periods when designing HIV programmes (˜5‐year funding cycles). We aim to explicitly quantify the cost of short‐term funding arrangements on the success of future HIV prevention programmes.Methods:Using mathematical models of HIV transmission in Kenya, we compare the impact of optimized combination prevention strategies under different constraints on investment over time. Each scenario has the same total budget for the 30‐year intervention period but the pattern of spending over time is allowed to vary. We look at the impact of programmes with decreasing, increasing or constant spending across 5‐year funding cycles for a 30‐year period. Interventions are optimized within each funding cycle such that strategies take a short‐term view of the epidemic. We compare these with two strategies with no spending pattern constraints: one with static intervention choices and another flexible strategy with interventions changed in year ten.Results and Discussion:For the same total 30‐year budget, greatest impact is achieved if larger initial prevention spending is offset by later treatment savings which leads to accumulating benefits in reduced infections. The impact under funding cycle constraints is determined by the extent to which greater initial spending is permitted. Short‐term funding constraints and funds held back to later years may reduce impact by up to 18% relative to the flexible long‐term strategy.Conclusions:Ensuring that funding arrangements are in place to support long‐term prevention strategies will make spending most impactful. Greater prevention spending now will bring considerable returns through reductions in new infections, greater population health and reductions in the burden on health services in the future.

Journal article

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