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

 

School of Public HealthWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

290 results found

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

Phillips AN, Cambiano V, Nakagawa F, Revill P, Jordan MR, Hallett TB, Doherty M, De Luca A, Lundgren JD, Mhangara M, Apollo T, Mellors J, Nichols B, Parikh U, Pillay D, de Wit TR, Sigaloff K, Havlir D, Kuritzkes DR, Pozniak A, van de Vijver D, Vitoria M, Wainberg MA, Raizes E, Bertagnolio Set al., 2018, Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study, LANCET HIV, Vol: 5, Pages: E146-E154, ISSN: 2352-3018

BackgroundThere is concern over increasing prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral therapy (ART) in low-income and middle-income countries. We assessed the effectiveness and cost-effectiveness of alternative public health responses in countries in sub-Saharan Africa where the prevalence of pretreatment drug resistance to NNRTIs is high.MethodsThe HIV Synthesis Model is an individual-based simulation model of sexual HIV transmission, progression, and the effect of ART in adults, which is based on extensive published data sources and considers specific drugs and resistance mutations. We used this model to generate multiple setting scenarios mimicking those in sub-Saharan Africa and considered the prevalence of pretreatment NNRTI drug resistance in 2017. We then compared effectiveness and cost-effectiveness of alternative policy options. We took a 20 year time horizon, used a cost effectiveness threshold of US$500 per DALY averted, and discounted DALYs and costs at 3% per year.FindingsA transition to use of a dolutegravir as a first-line regimen in all new ART initiators is the option predicted to produce the most health benefits, resulting in a reduction of about 1 death per year per 100 people on ART over the next 20 years in a situation in which more than 10% of ART initiators have NNRTI resistance. The negative effect on population health of postponing the transition to dolutegravir increases substantially with higher prevalence of HIV drug resistance to NNRTI in ART initiators. Because of the reduced risk of resistance acquisition with dolutegravir-based regimens and reduced use of expensive second-line boosted protease inhibitor regimens, this policy option is also predicted to lead to a reduction of overall programme cost.InterpretationA future transition from first-line regimens containing efavirenz to regimens containing dolutegravir formulations in adult ART initiators is predicted to

Journal article

Smith MK, Jewell BL, Hallett TB, Cohen MSet al., 2018, Treatment of HIV for the Prevention of Transmission in Discordant Couples and at the Population Level, HIV VACCINES AND CURE: THE PATH TOWARDS FINDING AN EFFECTIVE CURE AND VACCINE, Vol: 1075, Pages: 125-162, ISSN: 0065-2598

Journal article

Anderson S, Ghys PD, Ombam R, Hallett TBet al., 2017, HIV Prevention Where it is Needed Most: Comparison of Strategies for the Geographical Allocation of Interventions, Journal of the International AIDS Society, Vol: 20, ISSN: 1758-2652

IntroductionA strategic approach to the application of HIV prevention interventions is a core component of the UNAIDS Fast Track strategy to end the HIV epidemic by 2030. Central to these plans is a focus on high-prevalence geographies, in a bid to target resources to those in greatest need and maximize the reduction in new infections. Whilst this idea of geographical prioritization has the potential to improve efficiency, it is unclear how it should be implemented in practice. There are a range of prevention interventions which can be applied differentially across risk groups and locations, making allocation decisions complex. Here, we use mathematical modelling to compare the impact (infections averted) of a number of different approaches to the implementation of geographical prioritization of prevention interventions, similar to those emerging in policy and practice, across a range of prevention budgets.MethodsWe use geographically specific mathematical models of the epidemic and response in 48 counties and major cities of Kenya to project the impact of the different geographical prioritization approaches. We compare the geographical allocation strategies with a nationally uniform approach under which the same interventions must be applied across all modelled locations.ResultsWe find that the most extreme geographical prioritization strategy, which focuses resources exclusively to high-prevalence locations, may substantially restrict impact (41% fewer infections averted) compared to a nationally uniform approach, as opportunities for highly effective interventions for high-risk populations in lower-prevalence areas are missed. Other geographical allocation approaches, which intensify efforts in higher-prevalence areas whilst maintaining a minimum package of cost-effective interventions everywhere, consistently improve impact at all budget levels. Such strategies balance the need for greater investment in locations with the largest epidemics whilst ensuring higher

Journal article

McGillen JB, Sharp A, Honermann B, Millett G, Collins C, Hallett TBet al., 2017, Consequences of a changing US strategy in the global HIV investment landscape., AIDS, Vol: 31, Pages: F19-F23, ISSN: 0269-9370

OBJECTIVE: The global fight against HIV/AIDS in Africa has long been a focus of US foreign policy, but this could change if the federal budget for 2018 proposed by the US Office of Management and Budget is adopted. We aim to inform public and Congressional debate around this issue by evaluating the historical and potential future impact of US investment in the African HIV response. DESIGN/METHODS: We use a previously published mathematical model of HIV transmission to characterize the possible impact of a series of financial scenarios for the historical and future AIDS response across Sub-Saharan Africa. RESULTS: We find that US funding has saved nearly five million adults in Sub-Saharan Africa from AIDS-related deaths. In the coming 15 years, if current numbers on antiretroviral treatment are maintained without further expansion of programs (the proposed US strategy), nearly 26 million new HIV infections and 4.4 million AIDS deaths may occur. A 10% increase in US funding, together with ambitious domestic spending and focused attention on optimizing resources, can avert up to 22 million HIV infections and save 2.3 million lives in Sub-Saharan Africa compared with the proposed strategy. CONCLUSION: Our synthesis of available evidence shows that the United States has played, and could continue to play, a vital role in the global HIV response. Reduced investment could allow more than two million avoidable AIDS deaths by 2032, whereas continued leadership by the United States and other countries could bring UNAIDS targets for ending the epidemic into reach.

Journal article

Nayagam S, Sicuri E, Lemoine M, Easterbrook P, Conteh L, Hallett TB, Thursz Met al., 2017, Economic evaluations of HBV testing and treatment strategies and applicability to low and middle-income countries, BMC Infectious Diseases, Vol: 17, Pages: 107-116, ISSN: 1471-2334

Background: Many people living with chronic HBV infection remain undiagnosed until later stages of disease.Increasing testing and treatment rates form part of the strategy to respond to the WHO goal of eliminating viralhepatitis as a public health threat by 2030. However, achieving these ambitious targets is dependent on findingeffective and cost-effective methods of scale up strategies. The aim of this study was to undertake a narrativereview of the literature on economic evaluations of testing and treatment for HBV infection, to help inform thedevelopment of the 2017 WHO Hepatitis Testing Guidelines.Methods: We undertook a focussed literature review for economic evaluations on testing for HBV accompanied byantiviral treatment. The search was carried out in Pubmed and included only articles published after 2000 and writtenin English. We narratively synthesise the results and discuss the key drivers of cost-effectiveness and their applicabilityto low and middle-income countries (LMICs).Results: Nine published studies were included in this review, only one of which was performed in a low or middleincomesetting in West Africa. Eight studies were performed in high-income settings, seven among high risk groupsand one among the general population. The studies were heterogeneous in many respects including the populationand testing strategy under consideration, model structure and baselines parameters, willingness to pay thresholds andoutcome measures used. However, most studies found HBV testing and treatment to be cost-effective, even at lowHBsAg prevalence levels.Conclusions: Currently economic evaluations of HBV testing and treatment strategies in LMICs is lacking, thereforelimiting the ability to provide formal recommendations on the basis of cost-effectiveness alone. Further implementationresearch is needed in order to help guide national policy planning.

Journal article

Smit M, Cassidy R, Cozzi-Lepri A, Quiros-Roldan E, Girardi E, Mammone A, Antinori A, Saracino A, Bai F, Rusconi S, Magnani G, Castelli F, Prisculla H, d'Arminio Monforte A, Hallett TBet al., 2017, Projections of Non-Communicable Disease and Health Care Costs Among HIV-Positive Persons in Italy and the U.S.A: A Modelling Study, PLoS ONE, Vol: 12, ISSN: 1932-6203

BackgroundCountry-specific forecasts of the growing non-communicable disease (NCD) burden in ageing HIV-positive patients will be key to guide future HIV policies. We provided the first national forecasts for Italy and the Unites States of America (USA) and quantified direct cost of caring for these increasingly complex patients.Methods and SettingWe adapted an individual-based model of ageing HIV-positive patients to Italy and the USA, which followed patients on HIV-treatment as they aged and developed NCDs (chronic kidney disease, diabetes, dyslipidaemia, hypertension, non-AIDS malignancies, myocardial infarctions and strokes). The models were parameterised using data on 7,469 HIV-positive patients from the Italian Cohort Naïve to Antiretrovirals Foundation Study and 3,748 commercially-insured patients in the USA and extrapolated to national level using national surveillance data.ResultsThe model predicted that mean age of HIV-positive patients will increase from 46 to 59 in Italy and from 49 to 58 in the USA in 2015–2035. The proportion of patients in Italy and the USA diagnosed with ≥1 NCD is estimated to increase from 64% and 71% in 2015 to 89% and 89% by 2035, respectively, driven by moderate cardiovascular disease (CVD) (hypertension and dyslipidaemia), diabetes and malignancies in both countries. NCD treatment costs as a proportion of total direct HIV costs will increase from 11% to 23% in Italy and from 40% to 56% in the USA in 2015–2035.ConclusionsHIV patient profile in Italy and the USA is shifting to older patients diagnosed with multiple co-morbidity. This will increase NCD treatment costs and require multi-disciplinary patient management.

Journal article

McRobie ES, Matovu F, Nanyiti A, Nonvignon J, Abankwah D, Case K, Hallett TB, Hanefeld J, Conteh Let al., 2017, National responses to global health targets: Exploring policy transfer in the context of the UNAIDS '90-90-90' treatment targets in Ghana and Uganda, Health Policy and Planning, Vol: 33, Pages: 17-33, ISSN: 1460-2237

Global health organizations frequently set disease-specific targets with the goal of eliciting adoption at the national-level; consideration of the influence of target setting on national policies, programme and health budgets is of benefit to those setting targets and those intended to respond. In 2014, the Joint United Nations Programme on HIV/AIDS set ‘ambitious’ treatment targets for country adoption: 90% of HIV-positive persons should know their status; 90% of those on treatment; 90% of those achieving viral suppression. Using case studies from Ghana and Uganda, we explore how the target and its associated policy content have been adopted at the national level. That is whether adoption is in rhetoric only or supported by programme, policy or budgetary changes. We review 23 (14 from Ghana, 9 from Uganda) national policy, operational and strategic documents for the HIV response and assess commitments to ‘90–90–90’. In-person semi-structured interviews were conducted with purposively sampled key informants (17 in Ghana, 20 in Uganda) involved in programme-planning and resource allocation within HIV to gain insight into factors facilitating adoption of 90–90–90. Interviews were transcribed and analysed thematically, inductively and deductively, guided by pre-existing policy theories, including Dolowitz and Marsh’s policy transfer framework to describe features of the transfer and the Global Health Advocacy and Policy Project framework to explain observations. Regardless of notable resource constraints, transfer of the 90–90–90 targets was evident beyond rhetoric with substantial shifts in policy and programme activities. In both countries, there was evidence of attempts to minimize resource constraints by seeking programme efficiencies, prioritization of programme activities and devising domestic financing mechanisms; however, significant resource gaps persist. An effective health network, comprised

Journal article

Gregson S, Mugurungi O, Eaton J, Takaruza A, Rhead R, Maswera R, Mutsangwa J, Mayini J, Skovdal M, Schaefer R, Hallett T, Sherr L, Munyati S, Mason P, Campbell C, Garnett G, Nyamukapa Cet al., 2017, Documenting and explaining the HIV decline in east Zimbabwe: the Manicaland General Population Cohort, BMJ Open, Vol: 7, ISSN: 2044-6055

Purpose: The Manicaland Cohort was established to provide robust scientific data on HIV prevalence and incidence, patterns of sexual risk behaviour, and the demographic impact of HIV in a sub-Saharan African population subject to a generalised HIV epidemic. The aims were later broadened to include provision of data on the coverage and effectiveness of national HIV control programmes including antiretroviral treatment (ART).Participants: General population open cohort located in 12 sites in Manicaland, east Zimbabwe, representing 4 major socio-economic strata (small towns, agricultural estates, roadside settlements, and subsistence farming areas). 9,109 of 11,453 (79.5%) eligible adults (men 17-54 years; women 15-44 years) were recruited in a phased household census between July 1998 and January 2000. Five rounds of follow-up of the prospective household census and the open cohort were conducted at 2 or 3 year intervals between July 2001 and November 2013. Follow-up rates among surviving residents ranged between 77.0% (over 3 years) and 96.4% (2 years). Findings to date: HIV prevalence was 25.1% at baseline and had a substantial demographic impact with 10-fold higher mortality in HIV-infected adults than in uninfected adults and a reduction in the growth rate in the worst affected areas (towns) from 2.9% to 1.0%pa. HIV infection rates have been highest in young adults with earlier commencement of sexual activity and in those with older sexual partners and larger numbers of lifetime partners. HIV prevalence has since fallen to 15.8% and HIV incidence has also declined from 2.1% (1998-2003) to 0.63% (2009-2013) largely due to reduced sexual risk behaviour. HIV-associated mortality fell substantially after 2009 with increased availability of ART

Journal article

Smit M, van Zoest RA, Nichols BE, Vaartjes I, Smit C, van der Vallk M, van Sighem A, Wit FW, Hallett TB, Reiss Pet al., 2017, Cardiovascular disease prevention policy in HIV: recommendations from a modelling study, Clinical Infectious Diseases, Vol: 66, Pages: 743-750, ISSN: 1058-4838

BackgroundCardiovascular disease (CVD) is expected to contribute a large noncommunicable disease burden among human immunodeficiency virus (HIV)–infected people. We quantify the impact of prevention interventions on annual CVD burden and costs among HIV-infected people in the Netherlands.MethodsWe constructed an individual-based model of CVD in HIV-infected people using national ATHENA (AIDS Therapy Evaluation in The Netherlands) cohort data on 8791 patients on combination antiretroviral therapy (cART). The model follows patients as they age, develop CVD (by incorporating a CVD risk equation), and start cardiovascular medication. Four prevention interventions were evaluated: (1) increasing the rate of earlier HIV diagnosis and treatment; (2) avoiding use of cART with increased CVD risk; (3) smoking cessation; and (4) intensified monitoring and drug treatment of hypertension and dyslipidemia, quantifying annual number of averted CVDs and costs.ResultsThe model predicts that annual CVD incidence and costs will increase by 55% and 36% between 2015 and 2030. Traditional prevention interventions (ie, smoking cessation and intensified monitoring and treatment of hypertension and dyslipidemia) will avert the largest number of annual CVD cases (13.1% and 20.0%) compared with HIV-related interventions—that is, earlier HIV diagnosis and treatment and avoiding cART with increased CVD risk (0.8% and 3.7%, respectively)—as well as reduce cumulative CVD-related costs. Targeting high-risk patients could avert the majority of events and costs.ConclusionsTraditional CVD prevention interventions can maximize cardiovascular health and defray future costs, particularly if targeting high-risk patients. Quantifying additional public health benefits, beyond CVD, is likely to provide further evidence for policy development.

Journal article

McGillen J, Sharp A, Honermann B, Millett G, Collins C, Hallett Tet al., 2017, How changes in United States funding policies could impact the HIV epidemic in sub-Saharan Africa, Publisher: JOHN WILEY & SONS LTD, Pages: 64-65

Conference paper

Mangal TD, UNAIDS Working Group on CD4 Progression and Mortality Amongst HIV Seroconverters including the CASCADE Collaboration in EuroCoord, 2017, Joint estimation of CD4+ cell progression and survival in untreated individuals with HIV-1 infection., AIDS, Vol: 31, Pages: 1073-1082, ISSN: 0269-9370

OBJECTIVE: We compiled the largest dataset of seroconverter cohorts to date from 25 countries across Africa, North America, Europe, and Southeast/East (SE/E) Asia to simultaneously estimate transition rates between CD4 cell stages and death, in antiretroviral therapy (ART)-naive HIV-1-infected individuals. DESIGN: A hidden Markov model incorporating a misclassification matrix was used to represent natural short-term fluctuations and measurement errors in CD4 cell counts. Covariates were included to estimate the transition rates and survival probabilities for each subgroup. RESULTS: The median follow-up time for 16 373 eligible individuals was 4.1 years (interquartile range 1.7-7.1), and the mean age at seroconversion was 31.1 years (SD 8.8). A total of 14 525 individuals had recorded CD4 cell counts pre-ART, 1885 died, and 6947 initiated ART. Median (interquartile range) survival for men aged 20 years at seroconversion was 13.0 (12.4-13.4), 11.6 (10.9-12.3), and 8.3 years (7.9-8.9) in Europe/North America, Africa, and SE/E Asia, respectively. Mortality rates increase with age (hazard ratio 2.22, 95% confidence interval 1.84-2.67 for >45 years compared with <25 years) and vary by region (hazard ratio 2.68, 1.75-4.12 for Africa and 1.88, 1.50-2.35 for Asia compared with Europe/North America). CD4 cell decline was significantly faster in Asian cohorts compared with Europe/North America (hazard ratio 1.45, 1.36-1.54). CONCLUSION: Mortality and CD4 cell progression rates exhibited regional and age-specific differences, with decreased survival in African and SE/E Asian cohorts compared with Europe/North America and in older age groups. This extensive dataset reveals heterogeneities between regions and ages, which should be incorporated into future HIV models.

Journal article

Birger RB, Thuy L, Kouyos RD, Grenfell BT, Hallett TBet al., 2017, The impact of HCV therapy in a high HIV-HCV prevalence population: A modeling study on people who inject drugs in Ho Chi Minh City, Vietnam, PLoS ONE, Vol: 12, ISSN: 1932-6203

BackgroundHuman Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) coinfection is a majorglobal health problem especially among people who inject drugs (PWID), with significantclinical implications. Mathematical models have been used to great effect to shape HIVcare, but few have been proposed for HIV/HCV.MethodsWe constructed a deterministic compartmental ODE model that incorporated layers for HIVdisease progression, HCV disease progression and PWID demography. Antiretroviral therapy(ART) and Methadone Maintenance Therapy (MMT) scale-ups were modeled as from2016 and projected forward 10 years. HCV treatment roll-out was modeled beginning in2026, after a variety of MMT scale-up scenarios, and projected forward 10 years.ResultsOur results indicate that scale-up of ART has a major impact on HIV though not on HCV burden.MMT scale-up has an impact on incidence of both infections. HCV treatment roll-outhas a measurable impact on reductions of deaths, increasing multifold the mortality reductionsafforded by just ART/MMT scale-ups. ConclusionHCV treatment roll-out can have major and long-lasting effects on averting PWID deaths ontop of those averted by ART/MMT scale-up. Efficient intervention scale-up of HCV alongsideHIV interventions is critical in Vietnam.

Journal article

Cremin I, McKinnon L, Kimani J, Cherutich P, Gakii G, Muriuki F, Kripke K, Hecht R, Kiragu M, Smith J, Hinsley W, Gelmon L, Hallett Tet al., 2017, Including PrEP for key populations in combination HIV prevention: a mathematical modelling analysis of Nairobi as a case-study, Lancet HIV, Vol: 4, Pages: e214-e222, ISSN: 2405-4704

Background: The role of PrEP in combination HIV prevention remains uncertain. We aimed to identify an optimal portfolio of interventions to reduce HIV incidence for a given budget, and to identify the circumstances in which PrEP could be used in Nairobi, Kenya.Methods: A mathematical model was developed to represent HIV transmission among specific key populations (female sex workers (FSW), male sex workers (MSW), and men who have sex with men (MSM)) and among the wider population of Nairobi. The scale-up of existing interventions (condom promotion, anti-retroviral therapy (ART) and male circumcision) for key populations and the wider population as have occurred in Nairobi is represented. The model includes a detailed representation of a Pre-Exposure Prophylaxis (PrEP) intervention and is calibrated to prevalence and incidence estimates specific to key populations and the wider population. Findings: In the context of a declining epidemic overall but with a large sub-epidemic among MSM and MSW, an optimal prevention portfolio for Nairobi should focus on condom promotion for MSW and MSM in particular, followed by improved ART retention, earlier ART, and male circumcision as the budget allows. PrEP for MSW could enter an optimal portfolio at similar levels of spending to when earlier ART is included, however PrEP for MSM and FSW would be included only at much higher budgets. If PrEP for MSW cost as much $500, average annual spending on the interventions modelled would need to be less than $3·27 million for PrEP for MSW to be excluded from an optimal portfolio. Estimated costs per infection averted when providing PrEP to all FSW regardless of their risk of infection, and to high risk FSW only, are $65,160 (95% credible interval: $43,520 - $90,250) and $10,920 (95% credible interval: $4,700 - $51,560) respectively. Interpretation: PrEP could be a useful contribution to combination prevention, especially for underserved key populations in Nairobi. An ongoing demonst

Journal article

Alsallaq RA, Buttolph J, Cleland CM, Hallett T, Inwani I, Agot K, Kurth AEet al., 2017, The potential impact and cost of focusing HIV prevention on young women and men: A modeling analysis in western Kenya, PLOS ONE, Vol: 12, ISSN: 1932-6203

Objective:We compared the impact and costs of HIV prevention strategies focusing on youth (15–24 year-old persons) versus on adults (15+ year-old persons), in a high-HIV burden context of a large generalized epidemic.Design:Compartmental age-structured mathematical model of HIV transmission in Nyanza, Kenya.Interventions:The interventions focused on youth were high coverage HIV testing (80% of youth), treatment at diagnosis (TasP, i.e., immediate start of antiretroviral therapy [ART]) and 10% increased condom usage for HIV-positive diagnosed youth, male circumcision for HIV-negative young men, pre-exposure prophylaxis (PrEP) for high-risk HIV-negative females (ages 20–24 years), and cash transfer for in-school HIV-negative girls (ages 15–19 years). Permutations of these were compared to adult-focused HIV testing coverage with condoms and TasP.Results:The youth-focused strategy with ART treatment at diagnosis and condom use without adding interventions for HIV-negative youth performed better than the adult-focused strategy with adult testing reaching 50–60% coverage and TasP/condoms. Over the long term, the youth-focused strategy approached the performance of 70% adult testing and TasP/condoms. When high coverage male circumcision also is added to the youth-focused strategy, the combined intervention outperformed the adult-focused strategy with 70% testing, for at least 35 years by averting 94,000 more infections, averting 5.0 million more disability-adjusted life years (DALYs), and saving US$46.0 million over this period. The addition of prevention interventions beyond circumcision to the youth-focused strategy would be more beneficial if HIV care costs are high, or when program delivery costs are relatively high for programs encompassing HIV testing coverage exceeding 70%, TasP and condoms to HIV-infected adults compared to combination prevention programs among youth.Conclusion:For at least the next three decades, focusing in high burden set

Journal article

Wilson KC, Mhangara M, Dzangare J, Eaton JW, Hallett TB, Mugurungi O, Gregson Set al., 2017, Does nonlocal women's attendance at antenatal clinics distort HIV prevalence surveillance estimates in pregnant women in Zimbabwe?, AIDS, Vol: 31, Pages: S95-S102, ISSN: 0269-9370

Objective: The objective was to assess whether HIV prevalence measured among women attending antenatal clinics (ANCs) are representative of prevalence in the local area, or whether estimates may be biased by some women's choice to attend ANCs away from their residential location. We tested the hypothesis that HIV prevalence in towns and periurban areas is underestimated in ANC sentinel surveillance data in Zimbabwe.Methods: National unlinked anonymous HIV surveillance was conducted at 19 ANCs in Zimbabwe in 2000, 2001, 2002, 2004, 2006, 2009, and 2012. This data was used to compare HIV prevalence and nonlocal attendance levels at ANCs at city, town, periurban, and rural clinics in aggregate and also for individual ANCs.Results: In 2000, HIV prevalence at town ANCs (36.6%, 95% CI 34.4–38.9%) slightly underestimated prevalence among urban women attending these clinics (40.7%, 95% CI 37.6–43.9%). However, there was no distortion in HIV prevalence at either the aggregate clinic location or at individual clinics in more recent surveillance rounds. HIV prevalence was consistently higher in towns and periurban areas than in rural areas. Nonlocal attendance was high at town (26–39%) and periurban (53–95%) ANCs but low at city clinics (<10%). However, rural women attending ANCs in towns and periurban areas had higher HIV prevalence than rural women attending rural clinics, and were younger, more likely to be single, and less likely to be housewives.Conclusions: : In Zimbabwe, HIV prevalence among ANC attendees provides reliable estimates of HIV prevalence in pregnant women in the local area.

Journal article

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