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

205 results found

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: INT AIDS SOCIETY, Pages: 64-65, ISSN: 1758-2652

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

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

Case KK, Gregson S, Mahy M, Ghys PD, Hallett TBet al., 2017, Editorial: methodological developments in the Joint United Nations Programme on HIV/AIDS estimates, AIDS, Vol: 31, Pages: S1-S4, ISSN: 0269-9370

The Joint United Nations Programme on HIV/AIDS (UNAIDS) publishes estimates of the HIV epidemic every year [1]. For 2016, estimates are available for 160 countries representing 98% of the global population. These estimates are produced by countries with guidance from UNAIDS. The methods used in this process continue to evolve over time under the stewardship of the UNAIDS Reference Group on Estimates, Modelling and Projections [2].In 2014, the WHO convened the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) Working Group with the aim to define and promote good practice in reporting global health estimates [3]. The GATHER Statement is the outcome produced by this group. It defines a list of reporting requirements to allow for the accurate interpretation, and facilitate the appropriate use, of global health estimates [4]. UNAIDS fully endorses and supports the GATHER Statement.The current special supplement, which details the methods used to produce the 2016 UNAIDS estimates, further supports the routine publication of data sources and methods used as part of an open and transparent process. It provides updates of the evolving understanding of the data on which the estimates are based, the methods used to derive the estimates, justification of changes in these methods, and the sources of new data available to inform these modifications. It follows a series of such collections [5–10] which have documented and described the evolving methods used to produce the UNAIDS Global AIDS estimates since 2004.

Journal article

Buttolph J, Inwani I, Agot K, Cleland CM, Cherutich P, Kiarie JN, Osoti A, Celum CL, Baeten JM, Nduati R, Kinuthia J, Hallett TB, Alsallaq R, Kurth AEet al., 2017, Gender-Specific Combination HIV Prevention for Youth in High-Burden Settings: The MP3 Youth Observational Pilot Study Protocol., JMIR Research Protocols, Vol: 6, ISSN: 1929-0748

BACKGROUND: Nearly three decades into the epidemic, sub-Saharan Africa (SSA) remains the region most heavily affected by human immunodeficiency virus (HIV), with nearly 70% of the 34 million people living with HIV globally residing in the region. In SSA, female and male youth (15 to 24 years) are at a disproportionately high risk of HIV infection compared to adults. As such, there is a need to target HIV prevention strategies to youth and to tailor them to a gender-specific context. This protocol describes the process for the multi-staged approach in the design of the MP3 Youth pilot study, a gender-specific, combination, HIV prevention intervention for youth in Kenya. OBJECTIVE: The objective of this multi-method protocol is to outline a rigorous and replicable methodology for a gender-specific combination HIV prevention pilot study for youth in high-burden settings, illustrating the triangulated methods undertaken to ensure that age, sex, and context are integral in the design of the intervention. METHODS: The mixed-methods, cross-sectional, longitudinal cohort pilot study protocol was developed by first conducting a systematic review of the literature, which shaped focus group discussions around prevention package and delivery options, and that also informed age- and sex- stratified mathematical modeling. The review, qualitative data, and mathematical modeling created a triangulated evidence base of interventions to be included in the pilot study protocol. To design the pilot study protocol, we convened an expert panel to select HIV prevention interventions effective for youth in SSA, which will be offered in a mobile health setting. The goal of the pilot study implementation and evaluation is to apply lessons learned to more effective HIV prevention evidence and programming. RESULTS: The combination HIV prevention package in this protocol includes (1) offering HIV testing and counseling for all youth; (2) voluntary medical circumcision and condoms for males; (3)

Journal article

Elmes JAR, Skovdal M, Nhongo K, Ward H, Campbell C, Hallett TB, Nyamukapa C, White PJ, Gregson Set al., 2017, A reconfiguration of the sex trade: How social and structural changes in eastern Zimbabwe left women involved in sex work and transactional sex more vulnerable, PLOS One, Vol: 12, ISSN: 1932-6203

Understanding the dynamic nature of sex work is important for explaining the course of HIV epidemics. While health and development interventions targeting sex workers may alter the dynamics of the sex trade in particular localities, little has been done to explore how large-scale social and structural changes, such as economic recessions–outside of the bounds of organizational intervention–may reconfigure social norms and attitudes with regards to sex work. Zimbabwe’s economic collapse in 2009, following a period (2000–2009) of economic decline, within a declining HIV epidemic, provides a unique opportunity to study community perceptions of the impact of socio-economic upheaval on the sex trade. We conducted focus group discussions with 122 community members in rural eastern Zimbabwe in January-February 2009. Groups were homogeneous by gender and occupation and included female sex workers, married women, and men who frequented bars. The focus groups elicited discussion around changes (comparing contemporaneous circumstances in 2009 to their memories of circumstances in 2000) in the demand for, and supply of, paid sex, and how sex workers and clients adapted to these changes, and with what implications for their health and well-being. Transcripts were thematically analyzed. The analysis revealed how changing economic conditions, combined with an increased awareness and fear of HIV–changing norms and local attitudes toward sex work–had altered the demand for commercial sex. In response, sex work dispersed from the bars into the wider community, requiring female sex workers to employ different tactics to attract clients. Hyperinflation meant that sex workers had to accept new forms of payment, including sex-on-credit and commodities. Further impacting the demand for commercial sex work was a poverty-driven increase in transactional sex. The economic upheaval in Zimbabwe effectively reorganized the market for sex by reducing previousl

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 TBet al., 2017, PrEP for key populations in combination HIV prevention in Nairobi: a mathematical modelling study, LANCET HIV, Vol: 4, Pages: E214-E222, ISSN: 2352-3018

Journal article

Smith JA, Heffron R, Butler AR, Celum C, Baeten JM, Hallett TBet al., 2016, Could misreporting of condom use explain the observed association between injectable hormonal contraceptives and HIV acquisition risk?, Contraception, Vol: 95, Pages: 424-430, ISSN: 0010-7824

OBJECTIVE: Some observational studies have suggested an association between the use of hormonal contraceptives (HC) and HIV acquisition. One major concern is that differential misreporting of sexual behavior between HC users and nonusers may generate artificially inflated risk estimates. STUDY DESIGN: We developed an individual-based model that simulates the South African HIV serodiscordant couples analyzed for HC-HIV risk by Heffron et al. (2012). We varied the pattern of misreporting condom use between HC users and nonusers and reproduced the trial data under the assumption that HC use is not associated with HIV risk. The simulated data were analyzed using Cox proportional hazards models, adjusting for the reported level of condom use. RESULTS: If HC users overreport condom use more than nonusers, an apparent excess risk could be observed even without any biological effect of HC on HIV acquisition. With 45% overreporting by HC users (i.e., 9 out of every 20 sex acts reported with condoms are actually unprotected) and accurate condom reporting by nonusers, a true null effect can be inflated to give an observed hazard ratio (HR̂) of 2.0. In a different population with lower overall reported condom use, artificially high HR̂s can only be generated if non-HC users underreport condom use. CONCLUSION: Differential condom misreporting can theoretically produce inflated HR̂ values for an association between HC and HIV even without a true association. However, to produce a doubling of HIV risk that is entirely spurious requires substantially different levels of misreporting among HC users and nonusers, which may be unrealistic. IMPLICATIONS: Considerably differential amounts of condom use misreporting by HC users and nonusers would be needed to produce entirely spurious observed levels of excess HIV acquisition risk among HC users when there is actually no true association.

Journal article

McGillen JB, Anderson S-J, Hallett TB, 2016, Introducing optimism to models of resource allocation to reduce HIV incidence Reply, LANCET HIV, Vol: 4, Pages: E12-E12, ISSN: 2352-3018

Journal article

Nayagam S, Conteh L, Sicuri E, Shimakawa Y, Lemoine M, Hallett TB, Thursz Met al., 2016, Community-based screening and treatment for chronic hepatitis B in sub-Saharan Africa - Authors' reply., Lancet Global Health, Vol: 5, Pages: e35-e35, ISSN: 2214-109X

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., Including PrEP for key populations in combination HIV prevention: a mathematical modelling analysis of Nairobi as a case-study, Lancet HIV, 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

Garnett G, Hallett T, Gregson S, 2016, HIV Prevention Cascades: Identifying Gaps in the Delivery of HIV Prevention Interventions, Conference on HIV Research for Prevention (HIV R4P), Publisher: Mary Ann Liebert, Pages: 245-245, ISSN: 0889-2229

Conference paper

Olney JJ, Braitstein P, Eaton JW, Sang E, Nyambura M, Kimaiyo S, McRobie E, Hogan JW, Hallett TBet al., 2016, Evaluating strategies to improve HIV care outcomes in Kenya: a modelling study, Lancet HIV, Vol: 3, Pages: e592-e600, ISSN: 2405-4704

BackgroundWith expanded access to antiretroviral therapy (ART) in sub-Saharan Africa, HIV mortality has decreased, yet life-years are still lost to AIDS. Strengthening of treatment programmes is a priority. We examined the state of an HIV care programme in Kenya and assessed interventions to improve the impact of ART programmes on population health.MethodsWe created an individual-based mathematical model to describe the HIV epidemic and the experiences of care among adults infected with HIV in Kenya. We calibrated the model to a longitudinal dataset from the Academic Model Providing Access To Healthcare (known as AMPATH) programme describing the routes into care, losses from care, and clinical outcomes. We simulated the cost and effect of interventions at different stages of HIV care, including improvements to diagnosis, linkage to care, retention and adherence of ART, immediate ART eligibility, and a universal test-and-treat strategy.FindingsWe estimate that, of people dying from AIDS between 2010 and 2030, most will have initiated treatment (61%), but many will never have been diagnosed (25%) or will have been diagnosed but never started ART (14%). Many interventions targeting a single stage of the health-care cascade were likely to be cost-effective, but any individual intervention averted only a small percentage of deaths because the effect is attenuated by other weaknesses in care. However, a combination of five interventions (including improved linkage, point-of-care CD4 testing, voluntary counselling and testing with point-of-care CD4, and outreach to improve retention in pre-ART care and on-ART) would have a much larger impact, averting 1·10 million disability-adjusted life-years (DALYs) and 25% of expected new infections and would probably be cost-effective (US$571 per DALY averted). This strategy would improve health more efficiently than a universal test-and-treat intervention if there were no accompanying improvements to care ($1760 per DALY avert

Journal article

McGillen JB, Anderson SJ, Hallett TB, 2016, PrEP as a feature in the optimal landscape of combination HIV prevention in sub-Saharan Africa, Journal of the International AIDS Society, Vol: 19, ISSN: 1758-2652

INTRODUCTION: The new WHO guidelines recommend offering pre-exposure prophylaxis (PrEP) to people who are at substantial risk of HIV infection. However, where PrEP should be prioritised, and for which population groups, remains an open question. The HIV landscape in sub-Saharan Africa features limited prevention resources, multiple options for achieving cost saving, and epidemic heterogeneity. This paper examines what role PrEP should play in optimal prevention in this complex and dynamic landscape. METHODS: We use a model that was previously developed to capture subnational HIV transmission in sub-Saharan Africa. With this model, we can consider how prevention funds could be distributed across and within countries throughout sub-Saharan Africa to enable optimal HIV prevention (that is, avert the greatest number of infections for the lowest cost). Here, we focus on PrEP to elucidate where, and to whom, it would optimally be offered in portfolios of interventions (alongside voluntary medical male circumcision, treatment as prevention, and behaviour change communication). Over a range of continental expenditure levels, we use our model to explore prevention patterns that incorporate PrEP, exclude PrEP, or implement PrEP according to a fixed incidence threshold. RESULTS: At low-to-moderate levels of total prevention expenditure, we find that the optimal intervention portfolios would include PrEP in only a few regions and primarily for female sex workers (FSW). Prioritisation of PrEP would expand with increasing total expenditure, such that the optimal prevention portfolios would offer PrEP in more subnational regions and increasingly for men who have sex with men (MSM) and the lower incidence general population. The marginal benefit of including PrEP among the available interventions increases with overall expenditure by up to 14% (relative to excluding PrEP). The minimum baseline incidence for the optimal offer of PrEP declines for all population groups as expenditure

Journal article

Smit M, Cassidy R, Cozzi-Lepri A, Girardi E, Mammone A, Antinori A, Angarano G, Bai F, Rusconi S, Magnani G, Monforte AD, Hallett Tet al., 2016, Quantifying the future clinical burden of an ageing HIV-positive population in Italy: a mathematical modelling study, Publisher: INT AIDS SOCIETY, ISSN: 1758-2652

Conference paper

Smit M, Cassidy R, Hallett T, 2016, Quantifying the future clinical burden of an ageing HIV-positive population in the USA: a mathematical modelling, Publisher: INT AIDS SOCIETY, ISSN: 1758-2652

Conference paper

Odhiambo J, Onyango M, Stover J, Anderson S-J, Klein DJ, Hallett TB, Akullian A, Bershteyn Aet al., 2016, Evaluating the Impact of the Voluntary Medical Male Circumcision (VMMC) Program in Kenya, Conference on HIV Research for Prevention (HIV R4P), Publisher: MARY ANN LIEBERT, INC, Pages: 105-105, ISSN: 0889-2229

Conference paper

Garnett GP, Krishnaratne S, Rush SH, Hallett TB, Hargreaves JRet al., 2016, The Cost-effectiveness, Affordability and Impact of HIV Prevention: Concepts and Reviews, Conference on HIV Research for Prevention (HIV R4P), Publisher: MARY ANN LIEBERT, INC, Pages: 299-299, ISSN: 0889-2229

Conference paper

Bórquez A, Cori A, Pufall EL, Kasule J, Slaymaker E, Price A, Elmes J, Zaba B, Crampin AC, Kagaayi J, Lutalo T, Urassa M, Gregson S, Hallett TBet al., 2016, The Incidence Patterns Model to Estimate the Distribution of New HIV Infections in Sub-Saharan Africa: Development and Validation of a Mathematical Model., PLOS Medicine, Vol: 13, ISSN: 1549-1277

BACKGROUND: Programmatic planning in HIV requires estimates of the distribution of new HIV infections according to identifiable characteristics of individuals. In sub-Saharan Africa, robust routine data sources and historical epidemiological observations are available to inform and validate such estimates. METHODS AND FINDINGS: We developed a predictive model, the Incidence Patterns Model (IPM), representing populations according to factors that have been demonstrated to be strongly associated with HIV acquisition risk: gender, marital/sexual activity status, geographic location, "key populations" based on risk behaviours (sex work, injecting drug use, and male-to-male sex), HIV and ART status within married or cohabiting unions, and circumcision status. The IPM estimates the distribution of new infections acquired by group based on these factors within a Bayesian framework accounting for regional prior information on demographic and epidemiological characteristics from trials or observational studies. We validated and trained the model against direct observations of HIV incidence by group in seven rounds of cohort data from four studies ("sites") conducted in Manicaland, Zimbabwe; Rakai, Uganda; Karonga, Malawi; and Kisesa, Tanzania. The IPM performed well, with the projections' credible intervals for the proportion of new infections per group overlapping the data's confidence intervals for all groups in all rounds of data. In terms of geographical distribution, the projections' credible intervals overlapped the confidence intervals for four out of seven rounds, which were used as proxies for administrative divisions in a country. We assessed model performance after internal training (within one site) and external training (between sites) by comparing mean posterior log-likelihoods and used the best model to estimate the distribution of HIV incidence in six countries (Gabon, Kenya, Malawi, Rwanda, Swaziland, and Zambia) in the region. We subsequ

Journal article

Nayagam S, Thursz M, Sicuri E, Conteh L, Wiktor S, Low-Beer D, Hallett TBet al., 2016, Requirements for global elimination of hepatitis B: a modelling study., Lancet Infectious Diseases, Vol: 16, Pages: 1399-1408, ISSN: 1473-3099

BackgroundDespite the existence of effective prevention and treatment interventions, hepatitis B virus (HBV) infection continues to cause nearly 1 million deaths each year. WHO aspires to global control and elimination of HBV infection. We aimed to evaluate the potential impact of public health interventions against HBV, propose targets for reducing incidence and mortality, and identify the key developments required to achieve them.MethodsWe developed a simulation model of the global HBV epidemic, incorporating data on the natural history of HBV, prevalence, mortality, vaccine coverage, treatment dynamics, and demographics. We estimate the impact of current interventions and scaling up of existing interventions for prevention of infection and introducing wide-scale population screening and treatment interventions on the worldwide epidemic.FindingsVaccination of infants and neonates is already driving a large decrease in new infections; vaccination has already prevented 210 million new chronic infections by 2015 and will have averted 1·1 million deaths by 2030. However, without scale-up of existing interventions, our model showed that there will be a cumulative 63 million new cases of chronic infection and 17 million HBV-related deaths between 2015 and 2030 because of ongoing transmission in some regions and poor access to treatment for people already infected. A target of a 90% reduction in new chronic infections and 65% reduction in mortality could be achieved by scaling up the coverage of infant vaccination (to 90% of infants), birth-dose vaccination (to 80% of neonates), use of peripartum antivirals (to 80% of hepatitis B e antigen-positive mothers), and population-wide testing and treatment (to 80% of eligible people). These interventions would avert 7·3 million deaths between 2015 and 2030, including 1·5 million cases of cancer deaths. An elimination threshold for incidence of new chronic infections would be reached by 2090 worldwide. The a

Journal article

McGillen JB, Anderson SJ, Dybul MR, Hallett TBet al., 2016, Optimum resource allocation to reduce HIV incidence across sub-Saharan Africa: a mathematical modelling study, Lancet HIV, Vol: 3, Pages: e441-e448, ISSN: 2352-3018

BACKGROUND: Advances in HIV prevention methods offer promise to accelerate declines in incidence, but how these methods can be deployed to have the best effect on the heterogeneous landscape and drivers of the pandemic remains unclear. We postulated that use of epidemic heterogeneity to inform the allocation of resources for combination HIV prevention could enhance the impact of HIV funding across sub-Saharan Africa. METHODS: We developed a compartmental mathematical model of HIV transmission and disease progression by risk group to subnational resolution in 18 countries, capturing 80% of the adult HIV burden in sub-Saharan Africa. Adults aged 15-49 years were grouped by risk of HIV acquisition and transmission, and those older than 50 years were assumed to have negligible risk. For each top-level administrative division, we calibrated the model to historical data for HIV prevalence, sexual behaviours, treatment scale-up, and demographics. We then evaluated four strategies for allocation of prevention funding over a 15 year period from 2016 to 2030, which exploited epidemic differences between subnational regions to varying degrees. FINDINGS: For a $US20 billion representative expenditure over the 15 year period, scale-up of prevention along present funding channels could avert 5·3 million infections relative to no scale-up. Prioritisation of key populations could avert 3·7 million more infections than present funding channels, and additional prioritisation by within-country geography could avert 400 000 more infections. Removal of national constraints could avert a further 600 000 infections. Risk prioritisation has greater marginal impact than geographical prioritisation across multiple expenditure levels. However, targeting by both risk and geography is best for total impact and could achieve gains of up to three times more than present channels. A shift from the present pattern to the optimum pattern would rebalance resources towards more cost-effe

Journal article

Nayagam S, Conteh L, Sicuri E, Shimakawa Y, Tamba S, Suso P, Njie R, Njai H, Lemoine M, Hallett TB, Thursz Met al., 2016, Cost-effectiveness of community-based screening and treatment for chronic hepatitis B in The Gambia: an economic modelling analysis, Lancet Global Health, Vol: 4, Pages: e568-e578, ISSN: 2214-109X

Background: Despite the high burden of hepatitis B virus (HBV)infection in sub-Saharan Africa (SSA), a lack of access to widespreadscreening or treatment leads to most people remaining undiagnosed untillater stages of disease when prognosis is poor and treatment options arelimited. We evaluated the cost-effectiveness of community-based screeningand early treatment with antiviral therapy for HBV in The Gambia.Methods: An economic evaluation comparing adult community-based screeningusing a Hepatitis B surface antigen (HBsAg) rapid test and subsequent HBVantiviral therapy to a status quo scenario, where no treatment isavailable, was performed by combining a decision tree with a Markov statetransition model. This was parameterised with primary screening and costdata from the PROLIFICA study. A health provider perspective was takenand costs and health outcomes were discounted at 3% per annum.Findings: In The Gambia, where the HBsAg prevalence is 8.8% among thoseaged over 30 years old, adult screening and treatment for HBV, has anIncremental Cost-Effectiveness Ratio (ICER) of $540 per DisabilityAdjusted Life Year (DALY) averted, $645 per Life Year (LY) saved and $511per Quality Adjusted Life Year (QALY) gained, compared to status quo.These ICERs are in line with willingness-to-pay levels of one times thecountry's Gross Domestic Product (GDP) per capita ($487) per DALYaverted, whilst remaining robust, over a wide range of epidemiologicaland cost parameters.Interpretation: Adult community-based screening and treatment for HBV inthe Gambia is likely to be a cost-effective intervention with an ICERthat is comparable with those of HIV screening and treatmentinterventions in SSA. Even higher cost-effectiveness, may be achievablewith targeted facility-based screening, price reductions of drug and diagnostics and integration of HBV screening with other public healthinterventions.

Journal article

Dimitrov DT, Boily MC, Hallett TB, Albert J, Boucher C, Mellors JW, Pillay D, van de Vijver DAet al., 2016, How Much Do We Know about Drug Resistance Due to PrEP Use? Analysis of Experts’ Opinion and Its Influence on the Projected Public Health Impact, PLOS One, Vol: 11, ISSN: 1932-6203

BACKGROUND: Randomized controlled trials reported that pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine rarely selects for drug resistance. However, drug resistance due to PrEP is not completely understood. In daily practice, PrEP will not be used under the well-controlled conditions available in the trials, suggesting that widespread use of PrEP can result in increased drug resistance. METHODS: We surveyed expert virologists with questions about biological assumptions regarding drug resistance due to PrEP use. The influence of these assumptions on the prevalence of drug resistance and the fraction of HIV transmitted resistance was studied with a mathematical model. For comparability, 50% PrEP-coverage of and 90% per-act efficacy of PrEP in preventing HIV acquisition are assumed in all simulations. RESULTS: Virologists disagreed on the following: the time until resistance emergence (range: 20-180 days) in infected PrEP users with breakthrough HIV infections; the efficacy of PrEP against drug-resistant HIV (25%-90%); and the likelihood of resistance acquisition upon transmission (10%-75%). These differences translate into projections of 0.6%- 1% and 3.5%-6% infected individuals with detectable resistance 10 years after introducing PrEP, assuming 100% and 50% adherence, respectively. The rate of resistance emergence following breakthrough HIV infection and the rate of resistance reversion after PrEP use is discontinued, were the factors identified as most influential on the expected resistance associated with PrEP. Importantly, 17-23% infected individuals could virologically fail treatment as a result of past PrEP use or transmitted resistance to PrEP with moderate adherence. CONCLUSIONS: There is no broad consensus on quantification of key biological processes that underpin the emergence of PrEP-associated drug resistance. Despite this, the contribution of PrEP use to the prevalence of the detectable drug resistance is expected to be small. However, i

Journal article

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