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

235 results found

Forchini G, Lochen A, Hallett T, Aylin P, White P, Donnelly C, Ghani A, Ferguson N, Hauck Ket al., 2020, Report 28: Excess non-COVID-19 deaths in England and Wales between 29th February and 5th June 2020

There were 189,403 deaths from any cause reported in England from 29th February to 5th June 2020 inclusive, and 11,278 all-cause deaths in Wales over the same period. Of those deaths, 44,736 (23.6%) registered COVID-19 on the death certificate in England, and 2,294 (20.3%) in Wales, while 144,667 (76.4%) were not recorded as having been due to COVID-19 in England, and 8,984 (79.7%) in Wales. However, it could be that some of the ‘non-COVID-19’ deaths have in fact also been caused by COVID-19, either as the direct cause of death, or indirectly through provisions for the pandemic impeding access to care for other conditions. There is uncertainty in how many of the non-COVID-19 deaths were directly or indirectly caused by the pandemic. We estimated the excess deaths that were not recorded as associated with COVID-19 in the death certificate (excess non-COVID-19 deaths) as the deaths for which COVID-19 was not reported as the cause, compared to those we would have expected to occur had the pandemic not happened. Expected deaths were forecast with an analysis of historic trends in deaths between 2010 and April 2020 using data by the Office of National Statistics and a statistical time series model. According to the model, we expected 136,294 (95% CI 133,882 - 138,696) deaths in England, and 8,983 (CI 8,051 - 9,904) in Wales over this period, significantly fewer than the number of deaths reported. This means that there were 8,983 (95% CI 5,971 - 10,785) total excess non-COVID-19 deaths in England. For every 100 COVID-19 deaths during the period from 29th February to 5th June 2020 there were between 13 and 24 cumulative excess non-COVID-19 deaths. The proportion of cumulative excess non-COVID-19 deaths of all reported deaths during this period was 4.4% (95% CI 3.2% - 5.7%) in England, with small regional variations. Excess deaths were highest in the South East at 2,213 (95% CI 327 - 4,047) and in London at 1,937 (95% CI 896 - 3,010), respectively. There is no e

Report

Hogan A, Jewell B, Sherrard-Smith E, Watson O, Whittaker C, Hamlet A, Smith J, Winskill P, Verity R, Baguelin M, Lees J, Whittles L, Ainslie K, Bhatt S, Boonyasiri A, Brazeau N, Cattarino L, Cooper L, Coupland H, Cuomo-Dannenburg G, Dighe A, Djaafara A, Donnelly C, Eaton J, van Elsland S, Fitzjohn R, Fu H, Gaythorpe K, Green W, Haw D, Hayes S, Hinsley W, Imai N, Laydon D, Mangal T, Mellan T, Mishra S, Parag K, Thompson H, Unwin H, Vollmer M, Walters C, Wang H, Ferguson N, Okell L, Churcher T, Arinaminpathy N, Ghani A, Walker P, Hallett Tet al., Potential impact of the COVID-19 pandemic on HIV, TB and malaria in low- and middle-income countries: A Modelling Study, The Lancet Global Health, ISSN: 2214-109X

Background: COVID-19 has the potential to cause substantial disruptions to health services, including by cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions in services for human immunodeficiency virus (HIV), tuberculosis (TB) and malaria in low- and middle-income countries with high burdens of those disease could lead to additional loss of life. Methods: We constructed plausible scenarios for the disruptions that could be incurred during the COVID-19 pandemic and used established transmission models for each disease to estimate the additional impact on health that could be caused in selected settings.Findings: In high burden settings, HIV-, TB- and malaria-related deaths over five years may increase by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 pandemic. We estimate the greatest impact on HIV to be from interruption to antiretroviral therapy, which may occur during a period of high health system demand. For TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from any prolonged period of COVID-19 suppression interventions. We estimate that the greatest impact on malaria burden could come from interruption of planned net campaigns. These disruptions could lead to loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics.Interpretation: Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 pandemic.Funding: Bill & Melinda Gates Foundation, The Wellcome Trust, DFID, MRC

Journal article

Flaxman S, Mishra S, Gandy A, Unwin HJT, Mellan TA, Coupland H, Whittaker C, Zhu H, Berah T, Eaton JW, Monod M, Perez Guzman PN, Schmit N, Cilloni L, Ainslie K, Baguelin M, Boonyasiri A, Boyd O, Cattarino L, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Dorigatti I, van Elsland S, Fitzjohn R, Gaythorpe K, Geidelberg L, Grassly N, Green W, Hallett T, Hamlet A, Hinsley W, Jeffrey B, Knock E, Laydon D, Nedjati Gilani G, Nouvellet P, Parag K, Siveroni I, Thompson H, Verity R, Volz E, Walters C, Wang H, Watson O, Winskill P, Xi X, Walker P, Ghani AC, Donnelly CA, Riley SM, Vollmer MAC, Ferguson NM, Okell LC, Bhatt Set al., 2020, Estimating the effects of non-pharmaceutical interventions on COVID-19 in Europe, Nature, ISSN: 0028-0836

Following the emergence of a novel coronavirus1 (SARS-CoV-2) and its spread outside of China, Europe has experienced large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions such as closure of schools and national lockdowns. We study the impact of major interventions across 11 European countries for the period from the start of COVID-19 until the 4th of May 2020 when lockdowns started to be lifted. Our model calculates backwards from observed deaths to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. We use partial pooling of information between countries with both individual and shared effects on the reproduction number. Pooling allows more information to be used, helps overcome data idiosyncrasies, and enables more timely estimates. Our model relies on fixed estimates of some epidemiological parameters such as the infection fatality rate, does not include importation or subnational variation and assumes that changes in the reproduction number are an immediate response to interventions rather than gradual changes in behavior. Amidst the ongoing pandemic, we rely on death data that is incomplete, with systematic biases in reporting, and subject to future consolidation. We estimate that, for all the countries we consider, current interventions have been sufficient to drive the reproduction number Rt below 1 (probability Rt< 1.0 is 99.9%) and achieve epidemic control. We estimate that, across all 11 countries, between 12 and 15 million individuals have been infected with SARS-CoV-2 up to 4th May, representing between 3.2% and 4.0% of the population. Our results show that major non-pharmaceutical interventions and lockdown in particular have had a large effect on reducing transmission. Continued intervention should be considered to keep transmission of SARS-CoV-2 under control.

Journal article

Smith J, Garnett G, Hallett T, The potential impact of long-acting cabotegravir for HIV prevention in South Africa: a mathematical modelling study, Journal of Infectious Diseases, ISSN: 0022-1899

Journal article

Haacker M, Hallett T, Atun R, OnTime Horizons in Health Economic Evaluations, Health Policy and Planning, ISSN: 0268-1080

Journal article

Dighe A, Cattarino L, Cuomo-Dannenburg G, Skarp J, Imai N, Bhatia S, Gaythorpe K, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Charles G, Cooper L, Coupland H, Cucunuba Perez Z, Djaafara A, Dorigatti I, Eales O, Eaton J, van Elsland S, Ferreira Do Nascimento F, Fitzjohn R, Flaxman S, Fraser K, Geidelberg L, Green W, Hallett T, Hamlet A, Hauck K, Haw D, Hinsley W, Jeffrey B, Knock E, Laydon D, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Parag K, Pons Salort M, Ragonnet-Cronin M, Thompson H, Unwin H, Verity R, Whittaker C, Whittles L, Xi X, Ghani A, Donnelly C, Ferguson N, Riley Set al., 2020, Report 25: Response to COVID-19 in South Korea and implications for lifting stringent interventions, 25

While South Korea experienced a sharp growth in COVID-19 cases early in the global pandemic, it has since rapidly reduced rates of infection and now maintains low numbers of daily new cases. Despite using less stringent “lockdown” measures than other affected countries, strong social distancing measures have been advised in high incidence areas and a 38% national decrease in movement occurred voluntarily between February 24th - March 1st. Suspected and confirmed cases were isolated quickly even during the rapid expansion of the epidemic and identification of the Shincheonji cluster. South Korea swiftly scaled up testing capacity and was able to maintain case-based interventions throughout. However, individual case-based contact tracing, not associated with a specific cluster, was a relatively minor aspect of their control program, with cluster investigations accounting for a far higher proportion of cases: the underlying epidemic was driven by a series of linked clusters, with 48% of all cases in the Shincheonji cluster and 20% in other clusters. Case-based contacts currently account for only 11% of total cases. The high volume of testing and low number of deaths suggests that South Korea experienced a small epidemic of infections relative to other countries. Therefore, caution is needed in attempting to duplicate the South Korean response in settings with larger more generalized epidemics. Finding, testing and isolating cases that are linked to clusters may be more difficult in such settings.

Report

Unwin H, Mishra S, Bradley VC, Gandy A, Vollmer M, Mellan T, Coupland H, Ainslie K, Whittaker C, Ish-Horowicz J, Filippi S, Xi X, Monod M, Ratmann O, Hutchinson M, Valka F, Zhu H, Hawryluk I, Milton P, Baguelin M, Boonyasiri A, Brazeau N, Cattarino L, Charles G, Cooper L, Cucunuba Perez Z, Cuomo-Dannenburg G, Djaafara A, Dorigatti I, Eales O, Eaton J, van Elsland S, Fitzjohn R, Gaythorpe K, Green W, Hallett T, Hinsley W, Imai N, Jeffrey B, Knock E, Laydon D, Lees J, Nedjati Gilani G, Nouvellet P, Okell L, Ower A, Parag K, Siveroni I, Thompson H, Verity R, Walker P, Walters C, Wang Y, Watson O, Whittles L, Ghani A, Ferguson N, Riley S, Donnelly C, Bhatt S, Flaxman Set al., 2020, Report 23: State-level tracking of COVID-19 in the United States

our estimates show that the percentage of individuals that have been infected is 4.1% [3.7%-4.5%], with widevariation between states. For all states, even for the worst affected states, we estimate that less than a quarter of thepopulation has been infected; in New York, for example, we estimate that 16.6% [12.8%-21.6%] of individuals have beeninfected to date. Our attack rates for New York are in line with those from recent serological studies [1] broadly supportingour choice of infection fatality rate.There is variation in the initial reproduction number, which is likely due to a range of factors; we find a strong associationbetween the initial reproduction number with both population density (measured at the state level) and the chronologicaldate when 10 cumulative deaths occurred (a crude estimate of the date of locally sustained transmission).Our estimates suggest that the epidemic is not under control in much of the US: as of 17 May 2020 the reproductionnumber is above the critical threshold (1.0) in 24 [95% CI: 20-30] states. Higher reproduction numbers are geographicallyclustered in the South and Midwest, where epidemics are still developing, while we estimate lower reproduction numbersin states that have already suffered high COVID-19 mortality (such as the Northeast). These estimates suggest that cautionmust be taken in loosening current restrictions if effective additional measures are not put in place.We predict that increased mobility following relaxation of social distancing will lead to resurgence of transmission, keepingall else constant. We predict that deaths over the next two-month period could exceed current cumulative deathsby greater than two-fold, if the relationship between mobility and transmission remains unchanged. Our results suggestthat factors modulating transmission such as rapid testing, contact tracing and behavioural precautions are crucial to offsetthe rise of transmission associated with loosening of social distancing. Overall, we

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Winskill P, Whittaker C, Walker P, Watson O, Laydon D, Imai N, Cuomo-Dannenburg G, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Cattarino L, Ciavarella C, Cooper L, Coupland H, Cucunuba Perez Z, van Elsland S, Fitzjohn R, Flaxman S, Gaythorpe K, Green W, Hallett T, Hamlet A, Hinsley W, Knock E, Lees J, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Parag K, Thompson H, Unwin H, Wang Y, Whittles L, Xi X, Ferguson N, Donnelly C, Ghani Aet al., 2020, Report 22: Equity in response to the COVID-19 pandemic: an assessment of the direct and indirect impacts on disadvantaged and vulnerable populations in low- and lower middle-income countries, 22

The impact of the COVID-19 pandemic in low-income settings is likely to be more severe due to limited healthcare capacity. Within these settings, however, there exists unfair or avoidable differences in health among different groups in society – health inequities – that mean that some groups are particularly at risk from the negative direct and indirect consequences of COVID-19. The structural determinants of these are often reflected in differences by income strata, with the poorest populations having limited access to preventative measures such as handwashing. Their more fragile income status will also mean that they are likely to be employed in occupations that are not amenable to social-distancing measures, thereby further reducing their ability to protect themselves from infection. Furthermore, these populations may also lack access to timely healthcare on becoming ill. We explore these relationships by using large-scale household surveys to quantify the differences in handwashing access, occupation and hospital access with respect to wealth status in low-income settings. We use a COVID-19 transmission model to demonstrate the impact of these differences. Our results demonstrate clear trends that the probability of death from COVID-19 increases with increasing poverty. On average, we estimate a 32.0% (2.5th-97.5th centile 8.0%-72.5%) increase in the probability of death in the poorest quintile compared to the wealthiest quintile from these three factors alone. We further explore how risk mediators and the indirect impacts of COVID-19 may also hit these same disadvantaged and vulnerable the hardest. We find that larger, inter-generational households that may hamper efforts to protect the elderly if social distancing are associated with lower-income countries and, within LMICs, lower wealth status. Poorer populations are also more susceptible to food security issues - with these populations having the highest levels under-nourishment whilst also being

Report

Hogan A, Jewell B, Sherrard-Smith E, Vesga J, Watson O, Whittaker C, Hamlet A, Smith J, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Brazeau N, Cattarino L, Charles G, Cooper L, Coupland H, Cuomo-Dannenburg G, Dighe A, Djaafara A, Donnelly C, Dorigatti I, Eaton J, van Elsland S, Fitzjohn R, Fu H, Gaythorpe K, Green W, Haw D, Hayes S, Hinsley W, Imai N, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Ower A, Parag K, Pickles M, Stopard I, Thompson H, Unwin H, Verity R, Vollmer M, Walters C, Wang H, Wang Y, Whittles L, Winskill P, Xi X, Ferguson N, Churcher T, Arinaminpathy N, Ghani A, Walker P, Hallett Tet al., 2020, Report 19: The potential impact of the COVID-19 epidemic on HIV, TB and malaria in low- and middle-income countries

COVID-19 has the potential to cause disruptions to health services in different ways; through the health system becoming overwhelmed with COVID-19 patients, through the intervention used to slow transmission of COVID-19 inhibiting access to preventative interventions and services, and through supplies of medicine being interrupted. We aim to quantify the extent to which such disruptions in services for HIV, TB and malaria in high burden low- and middle-income countries could lead to additional loss of life. In high burden settings, HIV, TB and malaria related deaths over 5 years may be increased by up to 10%, 20% and 36%, respectively, compared to if there were no COVID-19 epidemic. We estimate the greatest impact on HIV to be from interruption to ART, which may occur during a period of high or extremely high health system demand; for TB, we estimate the greatest impact is from reductions in timely diagnosis and treatment of new cases, which may result from a long period of COVID-19 suppression interventions; for malaria, we estimate that the greatest impact could come from reduced prevention activities including interruption of planned net campaigns, through all phases of the COVID-19 epidemic. In high burden settings, the impact of each type of disruption could be significant and lead to a loss of life-years over five years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV/TB epidemics. Maintaining the most critical prevention activities and healthcare services for HIV, TB and malaria could significantly reduce the overall impact of the COVID-19 epidemic.

Report

Perez Guzman PN, Daunt A, Mukherjee S, Crook P, Forlano R, Kont M, Lochen A, Vollmer M, Middleton P, Judge R, Harlow C, Soubieres A, Cooke G, White P, Hallett T, Aylin P, Ferguson N, Hauck K, Thursz M, Nayagam ASet al., 2020, Report 17: Clinical characteristics and predictors of outcomes of hospitalised patients with COVID-19 in a London NHS Trust: a retrospective cohort study

Clinical characteristics and determinants of outcomes for hospitalised COVID-19 patients in the UK remain largely undescribed and emerging evidence suggests ethnic minorities might be disproportionately affected. We describe the characteristics and outcomes of patients hospitalised for COVID-19 in three large London hospitals with a multi-ethnic catchment population.We performed a retrospective cohort study on all patients hospitalised with laboratory-confirmed SARS-CoV-2 infection at Imperial College Healthcare NHS Trust between February 25 and April 5, 2020. Outcomes were recorded as of April 19, 2020. Logistic regression models, survival analyses and cumulative competing risk analyses were performed to evaluate factors associated with COVID-19 hospital mortality.Of 520 patients in this cohort (median age 67 years, (IQR 26) and 62% male), 302 (68%) had been discharged alive, 144 (32%) died and 74 (14%) were still hospitalised at the time of censoring. Increasing age (adjusted odds ratio [aOR] 2·16, 95%CI 1·50-3·12), severe hypoxia (aOR 3·75, 95%CI 1·80-7·80), low platelets (aOR 0·65, 95%CI 0.49·0·85), reduced estimated glomerular filtration rate (aOR 4·11, 95%CI 1·58-10·69), bilirubin >21mmol/L (aOR 2·32, 95%CI 1·05-5·14) and low albumin (aOR 0·77, 9%%CI 0·59-1·01) were associated with increased risk of in-hospital mortality. Individual comorbidities were not independently associated with risk of death. Regarding ethnicity, 209 (40%) were from a black and Asian minority, for 115 (22%) ethnicity was unknown and 196 (38%) patients were white. Compared to the latter, black patients were significantly younger and had less comorbidities. Whilst the crude OR of death of black compared to white patients was not significant (1·14, 95%CI 0·69-1·88, p=0.62), adjusting for age and comorbidity showed a trend towards significance

Report

Jewell B, Smith J, Hallett T, 2020, The potential impact of interruptions to HIV services: a modelling case study for South Africa, Publisher: medRxiv

The numbers of deaths caused by HIV could increase substantially if the COVID-19 epidemic leads to interruptions in the availability of HIV services. We compare publicly available scenarios for COVID-19 mortality with predicted additional HIV-related mortality based on assumptions about possible interruptions in HIV programs. An interruption in the supply of ART for 40% of those on ART for 3 months could cause a number of deaths on the same order of magnitude as the number that are anticipated to be saved from COVID-19 through social distancing measures. In contrast, if the disruption can be managed such that the supply and usage of ART is maintained, the increase in AIDS deaths would be limited to 1% over five years, although this could still be accompanied by substantial increases in new HIV infections if there are reductions in VMMC, oral PrEP use, and condom availability.

Working paper

Grassly N, Pons Salort M, Parker E, White P, Ainslie K, Baguelin M, Bhatt S, Boonyasiri A, Boyd O, Brazeau N, Cattarino L, Ciavarella C, Cooper L, Coupland H, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Donnelly C, Dorigatti I, van Elsland S, Ferreira Do Nascimento F, Fitzjohn R, Fu H, Gaythorpe K, Geidelberg L, Green W, Hallett T, Hamlet A, Hayes S, Hinsley W, Imai N, Jorgensen D, Knock E, Laydon D, Lees J, Mangal T, Mellan T, Mishra S, Nedjati Gilani G, Nouvellet P, Okell L, Ower A, Parag K, Pickles M, Ragonnet-Cronin M, Stopard I, Thompson H, Unwin H, Verity R, Vollmer M, Volz E, Walker P, Walters C, Wang H, Wang Y, Watson O, Whittaker C, Whittles L, Winskill P, Xi X, Ferguson Net al., 2020, Report 16: Role of testing in COVID-19 control

The World Health Organization has called for increased molecular testing in response to the COVID-19 pandemic, but different countries have taken very different approaches. We used a simple mathematical model to investigate the potential effectiveness of alternative testing strategies for COVID-19 control. Weekly screening of healthcare workers (HCWs) and other at-risk groups using PCR or point-of-care tests for infection irrespective of symptoms is estimated to reduce their contribution to transmission by 25-33%, on top of reductions achieved by self-isolation following symptoms. Widespread PCR testing in the general population is unlikely to limit transmission more than contact-tracing and quarantine based on symptoms alone, but could allow earlier release of contacts from quarantine. Immunity passports based on tests for antibody or infection could support return to work but face significant technical, legal and ethical challenges. Testing is essential for pandemic surveillance but its direct contribution to the prevention of transmission is likely to be limited to patients, HCWs and other high-risk groups.

Report

Nayagam AS, Chan P, Zhao K, Sicuri E, Wang X, Jia J, Wei L, Walsh N, Rodewald LE, Zhang G, Ailing W, Zhang L, Chang J, Hou C, Qiu Y, Sui B, Xiao Y, Zhuang H, Thursz M, Scano F, Low-Beer D, Schwartländer B, Wang Y, Hallett TBet al., Investment case for a comprehensive package of interventions against Hepatitis B in China; applied modelling to help national strategy planning, Clinical Infectious Diseases, ISSN: 1058-4838

Background:In2016,the first globalviralhepatitiselimination targetswere endorsed. Anestimated one-third of the world’schronic HBV infected population live in China and liver cancer is the sixth leading cause of mortality, but coverage of first line antiviral treatment was low. In 2015, China was one of the first countriesto initiate a consultative process for a renewed approach to viral hepatitis. We present the investment case for the scale-up of a comprehensive package of HBV interventions. Methods:Adynamic simulation modelof HBV was developedand used to simulate the Chinese HBV epidemic. We evaluated the impact, costs and return on investment of a comprehensive package of prevention and treatment interventions from a societal perspective, incorporating costs of management of end-stage liver disease and lost productivity costs. Results:Despitethe successes of historical vaccination scale-up since 1992, there will be a projected 60millionpeople still living with HBV in 2030 and 10 million HBV-related deaths, including 5.7millionHBV-related cancer deaths between 2015-2030. This could be reduced by 2.1million by highly active case-finding and optimal antiviral treatment regimens. The package of interventions is likely to have a positive return-on-investment to society, of 1.57US$ per US$ invested. Conclusions:Increases in HBV-related deaths for the next few decades pose a major public health threatin China. Active case-finding and access to optimal antiviral treatment is requiredto mitigate this risk. This investment case approachprovides a real-world example of howapplied modellingcansupportnational dialogue and inform policy planning.

Journal article

Flaxman S, Mishra S, Gandy A, Unwin H, Coupland H, Mellan T, Zhu H, Berah T, Eaton J, Perez Guzman P, Schmit N, Cilloni L, Ainslie K, Baguelin M, Blake I, Boonyasiri A, Boyd O, Cattarino L, Ciavarella C, Cooper L, Cucunuba Perez Z, Cuomo-Dannenburg G, Dighe A, Djaafara A, Dorigatti I, van Elsland S, Fitzjohn R, Fu H, Gaythorpe K, Geidelberg L, Grassly N, Green W, Hallett T, Hamlet A, Hinsley W, Jeffrey B, Jorgensen D, Knock E, Laydon D, Nedjati Gilani G, Nouvellet P, Parag K, Siveroni I, Thompson H, Verity R, Volz E, Walters C, Wang H, Wang Y, Watson O, Winskill P, Xi X, Whittaker C, Walker P, Ghani A, Donnelly C, Riley S, Okell L, Vollmer M, Ferguson N, Bhatt Set al., 2020, Report 13: Estimating the number of infections and the impact of non-pharmaceutical interventions on COVID-19 in 11 European countries

Following the emergence of a novel coronavirus (SARS-CoV-2) and its spread outside of China, Europe is now experiencing large epidemics. In response, many European countries have implemented unprecedented non-pharmaceutical interventions including case isolation, the closure of schools and universities, banning of mass gatherings and/or public events, and most recently, widescale social distancing including local and national lockdowns. In this report, we use a semi-mechanistic Bayesian hierarchical model to attempt to infer the impact of these interventions across 11 European countries. Our methods assume that changes in the reproductive number – a measure of transmission - are an immediate response to these interventions being implemented rather than broader gradual changes in behaviour. Our model estimates these changes by calculating backwards from the deaths observed over time to estimate transmission that occurred several weeks prior, allowing for the time lag between infection and death. One of the key assumptions of the model is that each intervention has the same effect on the reproduction number across countries and over time. This allows us to leverage a greater amount of data across Europe to estimate these effects. It also means that our results are driven strongly by the data from countries with more advanced epidemics, and earlier interventions, such as Italy and Spain. We find that the slowing growth in daily reported deaths in Italy is consistent with a significant impact of interventions implemented several weeks earlier. In Italy, we estimate that the effective reproduction number, Rt, dropped to close to 1 around the time of lockdown (11th March), although with a high level of uncertainty. Overall, we estimate that countries have managed to reduce their reproduction number. Our estimates have wide credible intervals and contain 1 for countries that have implemented all interventions considered in our analysis. This means that the reproducti

Report

Perez-Guzman PN, Chung MH, De Vuyst H, Dalal S, Mutai KK, Muthoni K, Kigen B, Kilonzo N, Hallett TB, Smit Met al., 2020, The impact of scaling up cervical cancer screening and treatment services among women living with HIV in Kenya: a modelling study, BMJ Global Health, Vol: 5, Pages: 1-10, ISSN: 2059-7908

Introduction We aimed to quantify health outcomes and programmatic implications of scaling up cervical cancer (CC) screening and treatment options for women living with HIV in care aged 18–65 in Kenya.Methods Mathematical model comparing from 2020 to 2040: (1) visual inspection with acetic acid (VIA) and cryotherapy (Cryo); (2) VIA and Cryo or loop excision electrical procedure (LEEP), as indicated; (3) human papillomavirus (HPV)-DNA testing and Cryo or LEEP; and (4) enhanced screening technologies (either same-day HPV-DNA testing or digitally enhanced VIA) and Cryo or LEEP. Outcomes measured were annual number of CC cases, deaths, screening and treatment interventions, and engaged in care (numbers screened, treated and cured) and five yearly age-standardised incidence.Results All options will reduce CC cases and deaths compared with no scale-up. Options 1–3 will perform similarly, averting approximately 28 000 (33%) CC cases and 7700 (27%) deaths. That is, VIA screening would yield minimal losses to follow-up (LTFU). Conversely, LTFU associated with HPV-DNA testing will yield a lower care engagement, despite better diagnostic performance. In contrast, option 4 would maximise health outcomes, averting 43 200 (50%) CC cases and 11 800 (40%) deaths, given greater care engagement. Yearly rescreening with either option will impose a substantial burden on the health system, which could be reduced by spacing out frequency to three yearly without undermining health gains.Conclusions Beyond the specific choice of technologies to scale up, efficiently using available options will drive programmatic success. Addressing practical constraints around diagnostics’ performance and LTFU will be key to effectively avert CC cases and deaths.

Journal article

Fu H, Lin H-H, Hallett TB, Arinaminpathy Net al., 2020, Explaining age disparities in tuberculosis burden in Taiwan: a modelling study, BMC Infectious Diseases, Vol: 20, ISSN: 1471-2334

BackgroundTuberculosis (TB) burden shows wide disparities across ages in Taiwan. In 2016, the age-specific notification rate in those older than 65 years old was about 100 times as much as in those younger than 15 years old (185.0 vs 1.6 per 100,000 population). Similar patterns are observed in other intermediate TB burden settings. However, driving mechanisms for such age disparities are not clear and may have importance for TB control efforts.MethodsWe hypothesised three mechanisms for the age disparity in TB burden: (i) older age groups bear a higher risk of TB progression due to immune senescence, (ii) elderly cases acquired TB infection during a past period of high transmission, which has since rapidly declined and thus contributes to little recent infections, and (iii) assortative mixing by age allows elders to maintain a higher risk of TB infection, while limiting spillover transmission to younger age groups. We developed a series of dynamic compartmental models to incorporate these mechanisms, individually and in combination. The models were calibrated to the TB notification rates in Taiwan over 1997–2016 and evaluated by goodness-of-fit to the age disparities and the temporal trend in the TB burden, as well as the deviance information criterion (DIC). According to the model performance, we compared contributions of the hypothesised mechanisms.ResultsThe ‘full’ model including all the three hypothesised mechanisms best captured the age disparities and temporal trend of the TB notification rates. However, dropping individual mechanisms from the full model in turn, we found that excluding the mechanism of assortative mixing yielded the least change in goodness-of-fit. In terms of their influence on the TB dynamics, the major contribution of the ‘immune senescence’ and ‘assortative mixing’ mechanisms was to create disparate burden among age groups, while the ‘declining transmission’ mechanism s

Journal article

Jewell BL, Smith JA, Padian NS, van de Wijgert JHHM, Gollub EL, Jones HE, Ralph LJ, Hallett TBet al., 2020, ECHO: context and limitations, The Lancet, Vol: 395, Pages: e25-e26, ISSN: 0140-6736

Journal article

Haacker M, Hallett T, Atun R, 2020, On discount rates for economic evaluations in global health, Health Policy and Planning, Vol: 35, Pages: 107-114, ISSN: 0268-1080

Choices on discount rates have important implications for the outcomes of economic evaluations of health interventions and policies. In global health, such evaluations typically apply a discount rate of 3 percent for health outcomes and costs, mirroring guidance developed for high‐income countries, notably the United States.The paper investigates the suitability of thes eguidelines for global health (i.e.,with a focus on low‐ and middle‐income countries), and seeks to identify best practice. Our analysis builds on an overview of the academic literature on discounting in health evaluations, existing academic or government‐related guidelines on discounting, are view on discount rates applied in economic evaluations in global health, and cross‐country macroeconomic data. The social discount rate generally applied in global health of 3 percent annually is in consistent with rates of economic growth experienced outside the most advanced economies. Forlow‐ and lower‐middle income countries, a discount rate of at least 5 percent is more appropriate, and one around 4 percent for upper‐middle income countries. Alternative approaches–e.g., motivated by the returns to alternative investments or by the cost of financing–could usefully be applied, dependent on policy context. The current practise could lead to systematic bias toward over‐valuing the future costs and health benefits of interventions. For health economic evaluations in global health, guidelines on discounting need to be adapted to take account of the different economic context of low‐ and middle‐income countries.

Journal article

Thomas R, Skovdal M, Gallizzi M, Schaefer R, Moorhouse L, Nyamukapa C, Maswera R, Mandizvidza P, Hallett T, Gregson Set al., 2020, Improving risk perception and uptake of voluntary medical male circumcision with peer-education sessions and incentives, in Manicaland, East Zimbabwe: study protocol for a pilot randomised trial, Trials, Vol: 21, ISSN: 1745-6215

BackgroundVoluntary medical male circumcision (VMMC) is a key component of combination HIV-prevention programmes. Several high-HIV-prevalence countries in sub-Saharan Africa, including Zimbabwe, are looking to scale up VMMC activities. There is limited evidence on how a combination of social learning from peer education by a role model with different behavioural incentives influences demand for VMMC in such settings.Methods/DesignThis matched-cluster randomised controlled trial with 1740 participants will compare two behavioural incentives against a control with no intervention. In the intervention clusters, participants will participate in an education session delivered by a circumcised young male (“role model”) on the risks of HIV infection and the benefits from medical male circumcision. All participants will receive contributions towards transport costs to access medical male circumcision at participating clinics. Via blocked randomisation, in the intervention clusters participants will be randomly assigned to receive one of two types of incentives – fixed cash payment or lottery payment – both conditional on undergoing surgical VMMC. In two sites, a community-led intervention will also be implemented to address social obstacles and to increase support from peers, families and social structures. Baseline measures of endpoints will be gathered in surveys. Follow-up assessment at 6 months will include self-reported uptake of VMMC triangulated with clinic data.DiscussionThis is the first trial to pilot-test social learning to improve risk perception and self-efficacy and to address the fear of pain associated with VMMC and possible present-biased preferences with front-loaded compensations as well as fixed or lottery-based cash payments. This study will generate important knowledge to inform HIV-prevention policies about the effectiveness of behavioural interventions and incentives, which could be easily scaled-up.Trial registrationThis tria

Journal article

Eaton JW, Brown T, Puckett R, Glaubius R, Mutai K, Bao L, Salomon JA, Stover J, Mahy M, Hallett TBet al., 2019, The estimation and projection package age-sex model and the r-hybrid model: new tools for estimating HIV incidence trends in sub-Saharan Africa., AIDS, Vol: 33, Pages: S235-S244, ISSN: 0269-9370

OBJECTIVES: Improve models for estimating HIV epidemic trends in sub-Saharan Africa (SSA). DESIGN: Mathematical epidemic model fit to national HIV survey and ANC sentinel surveillance (ANC-SS) data. METHODS: We modified EPP to incorporate age and sex stratification (EPP-ASM) to more accurately capture the shifting demographics of maturing HIV epidemics. Secondly, we developed a new functional form for the HIV transmission rate, termed 'r-hybrid', which combines a four-parameter logistic function for the initial epidemic growth, peak, and decline followed by a first-order random walk for recent trends after epidemic stabilization. We fitted the r-hybrid model along with previously developed r-spline and r-trend models to HIV prevalence data from household surveys and ANC-SS in 177 regions in 34 SSA countries. We used leave-one-out cross validation with household survey HIV prevalence to compare model predictions. RESULTS: The r-hybrid and r-spline models typically provided similar HIV prevalence trends, but sometimes qualitatively different assessments of recent incidence trends because of different structural assumptions about the HIV transmission rate. The r-hybrid model had the lowest average continuous ranked probability score, indicating the best model predictions. Coverage of 95% posterior predictive intervals was 91.5% for the r-hybrid model, versus 87.2 and 85.5% for r-spline and r-trend, respectively. CONCLUSION: The EPP-ASM and r-hybrid models improve consistency of EPP and Spectrum, improve the epidemiological assumptions underpinning recent HIV incidence estimates, and improve estimates and short-term projections of HIV prevalence trends. Countries that use general population survey and ANC-SS data to estimate HIV epidemic trends should consider using these tools.

Journal article

Eaton J, Brown T, Puckett R, Glaubius R, Mutai K, Bao L, Salomon J, Stover J, Mahy M, Hallett Tet al., 2019, The Estimation and Projection Package Age-Sex Model and the r-hybrid modelnew tools for estimating HIV incidence trends in sub-Saharan Africa, AIDS, Vol: 33, Pages: S235-S244, ISSN: 0269-9370

Objectives: Improve models for estimating HIV epidemic trends in sub-Saharan Africa (SSA).Design: Mathematical epidemic model fit to national HIV survey and ANC sentinel surveillance(ANC-SS) data.Methods: We modified EPP to incorporate age and sex stratification (EPP-ASM) to moreaccurately capture the shifting demographics of maturing HIV epidemics. Secondly, wedeveloped a new functional form, termed ‘r-hybrid’, for the HIV transmission rate whichcombines a four-parameter logistic function for the initial epidemic growth, peak, and declinefollowed by a first-order random walk for recent trends after epidemic stabilization. We fitted ther-hybrid model along with previously developed r-spline and r-trend models to HIV prevalencedata from household surveys and ANC-SS in 177 regions in 34 SSA countries. We used leaveone-out cross validation with household survey HIV prevalence to compare model predictions.Results: The r-hybrid and r-spline models typically provided similar HIV prevalence trends, butsometimes qualitatively different assessments of recent incidence trends due to differentstructural assumptions about the HIV transmission rate. The r-hybrid model had the lowestaverage continuous ranked probability score, indicating the best model predictions. Coverage of95% posterior predictive intervals was 91.5% for the r-hybrid model, versus 87.2% and 85.5%for r-spline and r-trend, respectively.Conclusions: The EPP-ASM and r-hybrid models improve consistency of EPP and Spectrum,improve the epidemiological assumptions underpinning recent HIV incidence estimates, andimprove estimates and short-term projections of HIV prevalence trends. Countries that usegeneral population survey and ANC-SS data to estimate HIV epidemic trends should considerusing these tools.

Journal article

Thomas R, Skovdal M, Galizzi MM, Schaefer R, Moorhouse L, Nyamukapa C, Maswera R, Mandizvidza P, Hallett T, Gregson Set al., 2019, Improving risk perception and uptake of pre-exposure prophylaxis (PrEP) through interactive feedback-based counselling with and without community engagement in young women in Manicaland, East Zimbabwe: study protocol for a pilot randomized trial, Trials, Vol: 20, ISSN: 1745-6215

BackgroundHIV incidence in adolescent girls and young women remains high in sub-Saharan Africa. Progresstowards uptake of HIV prevention methods remains low. Studies of oral PrEP have shown that uptakeand adherence may be low due to low risk perception and ambivalence around using antiretroviralsfor prevention. No evidence exists on whether an interactive intervention aimed at adjusting riskperception and addressing the uncertainty around PrEP will improve uptake. This pilot research trialaims to provide an initial evaluation of the impact of an interactive digital tablet-based counsellingsession, correcting risk perception and addressing ambiguity around availability, usability andeffectiveness of PrEP.Methods/DesignThis is a matched-cluster randomised controlled trial which will compare an interactive tablet-basededucation intervention against a control with no intervention. The study will be implemented in eightsites. In each site, two matched clusters of villages will be created. One cluster will be randomlyallocated to intervention. In two sites a community engagement intervention will also be implementedto address social obstacles and to increase support from peers, families and social structures. 1,200HIV-negative young women 18-24 years, not on PrEP at baseline will be eligible. Baseline measures ofendpoints will be gathered in surveys. Follow-up assessment at six months will include bio-markers ofPrEP uptake and surveys.DiscussionThis will be the first randomized controlled trial to determine whether interactive feedbackcounselling leads to uptake of HIV prevention methods such as PrEP and reduces risky sexualbehaviour. If successful, policymakers could consider such an intervention in school-based educationcampaigns or as post- HIV-testing counselling for young people.Trial RegistrationThis trial has been registered on clinicaltrials.gov on 21/06/2018 (identifier: NCT03565575).https://clinicaltrials.gov/ct2/show/NCT03565575

Journal article

Smit M, Perez-Guzman P, Mutai KK, Cassidy R, Kibachio J, Kilonzo N, Hallett TBet al., Mapping the current and future non-communicable disease burden in Kenya by HIV status: a modelling study, Clinical Infectious Diseases, ISSN: 1058-4838

Background:Then on-communicable disease (NCD) burden in Kenya is not well characterised, despite estimates needed to identify future health priorities. We aimto quantify current and future NCD burden in Kenya by HIV status. Methods: Original systematic reviews (SRs) and meta-analyses of prevalence/incidence of cardiovascular disease (CVD), chronic kidney disease, depression, diabetes, high total cholesterol, hypertension, human papillomavirus infection and related pre-cancerous stages in Kenya were carried out. An individual-based model was developed, simulating births, deaths, HIV-diseaseand treatment, aforementioned NCDs and cancers. The model was parameterised using SR, epidemiological national and regional surveillance data. NCD burden was quantified for 2018-2035 by HIV statusamongst adults. Findings: SRsidentified prevalence/incidence data for eachNCD, except ischemic heart disease. The model estimates that 51% of Kenyan adults currently suffer from ≥1 NCD, with a higher burden in People Living with HIV (PLHIV)compared to HIV-negative (62% versus 51%), driven by theirhigher age profile and partlyby HIV-related risk for NCDs. Hypertension and high total cholesterolarethe main NCD drivers(adult prevalence of 20·5% (5·3 million) and 9·0% (2·3 million)), with CVD and cancers the main causesof death. The burden is projectedto increase by 2035 (56% in HIV-negative; 71% in PLHIV), with population growth doublingthe number of people needing services (15·4 million to 28·1million)by 2035. Conclusions:NCD services will need to be expanded in Kenya. Guidelines in Kenya already support provision of these amongst both the general and HIV-positive population, however coverage remains low.

Journal article

Hallett T, Hauck K, 2019, The Global Fund impact, The Lancet, Vol: 394, Pages: 1708-1709, ISSN: 0140-6736

Journal article

Beacroft L, Smith JA, Hallett TB, 2019, What impact could DMPA use have had in South Africa and how might its continued use affect the future of the HIV epidemic?, Journal of the International AIDS Society, Vol: 22, Pages: 1-6, ISSN: 1758-2652

IntroductionSome studies suggest that use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase susceptibility to HIV infection. We aim to determine the influence that such an association could have had on the HIV epidemic in South Africa.MethodsWe simulate the heterosexual adult HIV epidemic in South Africa using a compartmental model stratified by age, behavioural risk group, sex, male circumcision status and contraceptive use. We model two possible scenarios: (1) The “With Effect” scenario assumes that DMPA increases susceptibility to HIV infection by 1.20‐fold (95% confidence interval 1.06 to 1.36) based on a combination of the results of a recent randomised controlled trial (ECHO trial) and a number of observational studies. (2) The “No Effect” scenario assumes that DMPA has no effect on HIV acquisition risk. We calculate the difference in HIV‐related outcomes between the With Effect and No Effect scenarios to determine the potential impact that DMPA use could have had on the HIV epidemic.ResultsA causal association between DMPA and HIV acquisition could have caused 430,000 (90% of model runs 160,000 to 960,000) excess HIV infections and 230,000 (90,000 to 470,000) AIDS deaths in South Africa from 1980 to 2017. These figures represent 4.3% (1.6% to 9.6%) and 6.9% (2.6% to 15.2%) of the total modelled estimates of HIV infections and AIDS deaths respectively in South Africa in that period. Of the additional infections, 36% (25% to 48%) would have occurred among men. If DMPA use continues at current levels, a potential causal association could cause an additional 130,000 (50,000 to 270,000) infections between 2018 and 2037. The excess infections would have required an additional 640,000 (190,000 to 1,660,000) years of ART from 1980 to 2017, and a further 2,870,000 (890,000 to 7,270,000) years of ART from 2018 to 2037.ConclusionsIf there is a causal association between DMPA use and HIV risk, it could have subs

Journal article

Stopard IJ, Hauck K, Hallett TB, 2019, The influence of constraints on the efficient allocation of resources for HIV prevention: authors' response, AIDS, Vol: 33, Pages: 1950-1951, ISSN: 0269-9370

Journal article

Case K, Gomez G, Hallett T, 2019, The impact, cost and cost-effectiveness of oral pre-exposure prophylaxis in sub-Saharan Africa: a scoping review of modelling contributions and way forward, Journal of the International AIDS Society, Vol: 22, ISSN: 1758-2652

Introduction: Oral pre-exposure prophylaxis (PrEP) is a new form of HIV prevention being considered for inclusion in national prevention portfolios. Many mathematical modelling studies have been undertaken that speak to the impact, cost and cost-effectiveness of PrEP programmes. We assess the available evidence from mathematical modelling studies to inform programme planning and policy decision making for PrEP and further research directions.Methods: We conducted a scoping review of the published modelling literature. Articles published in English which modelled oral PrEP in sub-Saharan Africa, or non-specific settings with relevance to generalised HIV epidemic settings, were included. Data were extracted for the strategies of PrEP use modelled, and the impact, cost and cost-effectiveness of PrEP for each strategy. We define an algorithm to assess the quality and relevance of studies included, summarise the available evidence and identify the current gaps in modelling. Recommendations are generated for future modelling applications and data collection.Results and discussion: We reviewed 1,924 abstracts and included 44 studies spanning 2007 to 2017. Modelling has reported that PrEP can be a cost-effective addition to HIV prevention portfolios for some use cases, but also that it would not be cost-effective to fund PrEP before other prevention intervention are expanded. However, our assessment of the quality of the modelling indicates cost-effectiveness analyses failed to comply with standards of reporting for economic evaluations and the assessment of relevance highlighted that both key parameters and scenarios are now outdated. Current evidence gaps include modelling to inform service development using updated programmatic information and ex post modelling to evaluate and inform efficient deployment of resources in support of PrEP, especially among key populations, using direct evidence of cost, adherence and uptake patterns.Conclusions: Updated modelling which more

Journal article

Cooke GS, Hallett TB, 2019, Pricing viral hepatitis as part of universal health coverage, The Lancet Global Health, Vol: 7, Pages: e1148-e1149, ISSN: 2214-109X

Journal article

Moorhouse L, Schaefer R, Thomas R, Nyamukapa C, Skovdal M, Hallett T, Gregson Set al., 2019, Application of the HIV prevention cascade to identify, develop,and evaluate interventions to improve use of prevention methods:Examples from a study in east Zimbabwe, Journal of the International AIDS Society, Vol: 22, Pages: 86-92, ISSN: 1758-2652

Introduction: The HIV prevention cascade could be used in developing interventions to strengthen implementation of efficacious HIV prevention methods but its practical utility needs to be demonstrated. We propose a standardised approach to using the cascade to guide identification and evaluation of interventions and demonstrate its feasibility through a project to develop interventions to improve use of HIV prevention methods by adolescent girls and young women (AGYW) and potential male partners in east Zimbabwe.Discussion: We propose a six-step approach to using a published generic HIV prevention cascade formulation to develop interventions to increase motivation to use, access to and effective use of an HIV prevention method. The six steps are: (1) measure the HIV prevention cascade for the chosen population and method; (2) identify gaps in the cascade; (3) identify explanatory factors (barriers) contributing to observed gaps; (4) review literature to identify relevant theoretical frameworks and interventions; (5) tailor interventions to the local context; and (6) implement and evaluate the interventions using the cascade steps and explanatory factors as outcome indicators in the evaluation design. In the Zimbabwe example, steps 1-5 aided development of four interventions to overcome barriers to effective use of PrEP in AGYW (15-24 years) and VMMC in male partners (15-29). For young men, prevention cascade analyses identified gaps in motivation and access (due to transport costs/lost income) as barriers to VMMC uptake, so an intervention was designed including financial incentives and an education session. For AGYW, gaps in motivation (particularly lack of risk perception) and access were identified as barriers to PrEP uptake: an interactive counselling game was developed addressing these barriers. A text messaging intervention was developed to improve adherence to PrEP among AGYW, addressing reasons underlying lack of effective PrEP use through improving the capa

Journal article

Phillips AN, Cambiano V, Nakagawa F, Bansi-Matharu L, Wilson D, Jani I, Apollo T, Sculpher M, Hallett T, Kerr C, van Oosterhout JJ, Eaton J, Estill J, Williams B, Doi N, Cowan F, Keiser O, Ford D, Hatzold K, Barnabas R, Ayles H, Meyer-Rath G, Nelson L, Johnson CC, Baggaley R, Fakoya A, Jahn A, Revill Pet al., 2019, Cost-per-diagnosis as a metric for monitoring cost effectiveness of HIV testing programmes in low income settings in southern Africa: health economic and modelling analysis, Journal of the International AIDS Society, Vol: 22, Pages: 1-10, ISSN: 1758-2652

Introduction: As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost effective. To guide their HIV testing programmes,countries require appropriatemetrics that can be measured. The cost-per-diagnosisis potentially a useful metric. Methods:We simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of “core” testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) “core” testing as above plus “additional-testing”, for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than thosewithout HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosisand the incremental cost-effectiveness ratio(ICER) of the additional-testingpolicy. Discount rate 3%; costs in 2018 $US. Results:There was a strong graded relationship between the cost-per-diagnosisand the ICER. Overall, the ICERwas below $500 per-DALY-averted (the cost effectiveness threshold used in primary analysis) so long as thecost-per-diagnosiswas below $315. This thresholdcost-per-diagnosiswas similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restrictingto women, additional-testingdid not appear cost-effective even at acost-per-diagnosisof below $50, while restrictingto men additional-testingwas cost effective up to a cost-per-diagnosisof $585. Thethreshold cost for testing in men fell to $256 when the cost effectiveness threshold was $300instead of $5

Journal article

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