Imperial College London

Jeff Eaton

Faculty of MedicineSchool of Public Health

Senior Lecturer in HIV Epidemiology
 
 
 
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Contact

 

jeffrey.eaton

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
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80 results found

Kufa T, Shubber Z, MacLeod W, Takuva S, Carmona S, Bor J, Gorgens M, Pillay Y, Puren A, Eaton J, Fraser-Hurt Net al., CD4 count recovery and associated factors among individuals enrolled in the South African antiretroviral therapy programme: an analysis of national laboratory based data, PLoS ONE, ISSN: 1932-6203

JOURNAL ARTICLE

Nabukalu D, Reniers G, Risher KA, Blom S, Slaymaker E, Kabudula C, Zaba B, Nalugoda F, Kigodzi G, Makumbi F, Serwadda D, Reynolds SJ, Marston M, Eaton J, Gray R, Wawer M, Sewankambo N, Lutalo Tet al., Population-level adult mortality following the expansion of antiretroviral therapy in Rakai, Uganda, Population Studies, ISSN: 0032-4728

There are limited data on the impact of antiretroviral therapy (ART) on population-level adult mortality in sub-Saharan Africa. We analysed data for 2000–14 from the Rakai Community Cohort Study (RCCS) in Uganda, where free ART was scaled up after 2004. Using non-parametric and parametric (Weibull) survival analysis, we estimated trends in average person-years lived between exact ages 15 and 50, per capita life-years lost to HIV, and the mortality hazards of people living with HIV (PLHIV). Between 2000 and 2014, average adult life-years lived before age 50 increased significantly, from 26.4 to 33.5 years for all women and from 28.6 to 33.8 years for all men. As of 2014, life-years lost to HIV had declined significantly, to 1.3 years among women and 0.4 years among men. Following the roll-out of ART, mortality reductions among PLHIV were initially larger in women than men, but this is no longer the case

JOURNAL ARTICLE

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

JOURNAL ARTICLE

Dwyer-Lindgren L, Cork MA, Sligar A, Steuben KM, Wilson KF, Provost NR, Mayala BK, VanderHeide JD, Collison ML, Hall JB, Biehl MH, Carter A, Frank T, Douwes-Schultz D, Burstein R, Casey DC, Deshpande A, Earl L, El Bcheraoui C, Farag TH, Henry NJ, Kinyoki D, Marczak LB, Nixon MR, Osgood-Zimmerman A, Pigott D, Reiner RC, Ross JM, Schaeffer LE, Smith DL, Davis Weaver N, Wiens KE, Eaton JW, Justman JE, Opio A, Sartorius B, Tanser F, Wabiri N, Piot P, Murray CJL, Hay SIet al., 2019, Mapping HIV prevalence in sub-Saharan Africa between 2000 and 2017, Nature, ISSN: 0028-0836

HIV/AIDS is a leading cause of disease burden in sub-Saharan Africa. Existing evidence has demonstrated that there is substantial local variation in the prevalence of HIV; however, subnational variation has not been investigated at a high spatial resolution across the continent. Here we explore within-country variation at a 5 × 5-km resolution in sub-Saharan Africa by estimating the prevalence of HIV among adults (aged 15-49 years) and the corresponding number of people living with HIV from 2000 to 2017. Our analysis reveals substantial within-country variation in the prevalence of HIV throughout sub-Saharan Africa and local differences in both the direction and rate of change in HIV prevalence between 2000 and 2017, highlighting the degree to which important local differences are masked when examining trends at the country level. These fine-scale estimates of HIV prevalence across space and time provide an important tool for precisely targeting the interventions that are necessary to bringing HIV infections under control in sub-Saharan Africa.

JOURNAL ARTICLE

Eaton J, Terris-Prestholt F, Cambiano V, Sands A, Baggaley R, Hatzold K, Corbett E, Kalua T, Jahn A, Johnson CCet al., Optimizing HIV testing services in sub-Saharan Africa: Cost and performance of verification testing with HIV self-tests and tests for triage, Journal of the International AIDS Society, ISSN: 1758-2652

Introduction:Strategies employinga single rapid diagnostic test (RDT) such as HIV self-testing (HIVST)or ‘test for triage’ (T4T)areproposed to increase HIV testing programme impact.Current guidelines recommend serial testing with two or three RDTs for HIV diagnosis, followed by retestingwith the same algorithmto verify HIV-positive statusbefore anti-retroviral therapy (ART) initiation. We investigated whether clientspresenting to HTS following a single reactive RDTmust undergo thediagnostic algorithm twice to diagnose and verify HIV-positive status, or whether a diagnosis with the setting-specific algorithm is adequate for ART initiation.Methods: We calculated (1)expected number of false-positive (FP) misclassifications per 10,000 HIV negative persons tested,(2)positive predictive value (PPV) of the overall HIV testingstrategy compared to WHO recommended PPV ≥99%, and (3) expected cost per FPmisclassified person identified by additional verification testingin a typical low-/middle-income setting, compared to the expected lifetime ART cost of $3000. Scenarios considered were: 10% prevalence using two serial RDTsfor diagnosis,1% prevalence using three serial RDTs,and calibrationusing programmatic data from Malawi in 2017where theproportion of people testing HIV positive in facilities was 4%. Results: In the 10% HIV prevalence settingwith a triage test, the expected number ofFP misclassifications was0.86 per 10,000 tested without verification testing and the PPV was 99.9%. In the 1% prevalence setting, expected FP misclassifications were 0.19 with 99.8% PPV, and in the Malawi 2017 calibrated setting the expected misclassifications were 0.08 with 99.98% PPV. The cost per FP identified by verification testing was $5,879, $3,770, and $24,259, respectively. Results were sensitive to assumptions about accuracy of self-reported reactive results and whether reactive triage test results influenced biased interpretation of subsequent RDT results by the HTS provid

JOURNAL ARTICLE

Eaton J, Grebe E, Welte A, Juwara L, Ongarello Set al., 2018, Prevalence and Incidence Calculator (UNAIDS RG)

Calculates HIV incidence from prevalence survey data that include biomarkers of recent infection.Built using inctools for the UNAIDS Reference Group on Estimates, Modelling and Projections.The tool can be accessed at https://incidence.shinyapps.io/incidence_calculator/.

SOFTWARE

Rentsch C, Reniers G, Machemba R, Slaymaker E, Marston M, Wringe A, Eaton J, Gourlay A, Rice B, Kabadula C, Urassa M, Todd J, Zaba Bet al., 2018, Non-disclosure of HIV testing history in population-based surveys: implications for estimating a UNAIDS 90-90-90 target, Global Health Action, Vol: 11, ISSN: 1654-9880

Background: HIV/AIDS programmes and organisations around the world use routinely updated estimates of the UNAIDS 90-90-90 targets to track progress and prioritise further programme implementation. Any bias in these estimates has the potential to mislead organisations on where gaps exist in HIV testing and treatment programmes.Objective: To measure the extent of undisclosed HIV testing history and its impact on estimating the proportion of people living with HIV (PLHIV) who know their HIV status (the ‘first 90’ of the UNAIDS 90-90-90 targets).Methods: We conducted a retrospective cohort study using population-based HIV serological surveillance conducted between 2010 and 2016 and linked, directly observed HIV testing records in Kisesa, Tanzania. Generalised estimating equations logistic regression models were used to detect associations with non-disclosure of HIV testing history adjusting for demographic, behavioural, and clinical characteristics. We compared estimates of the ‘first 90’ using self-reported survey data only and augmented estimates using information from linked records to quantify the absolute and relative impact of undisclosed HIV testing history.Results: Numbers of participants in each of the survey rounds ranged from 7171 to 7981 with an average HIV prevalence of 6.9%. Up to 33% of those who tested HIV-positive and 34% of those who tested HIV-negative did not disclose their HIV testing history. The proportion of PLHIV who reported knowing their status increased from 34% in 2010 to 65% in 2016. Augmented estimates including information from directly observed testing history resulted in an absolute impact of 6.7 percentage points and relative impact of 12.4%.Conclusions: In this population, self-reported testing history in population-based HIV serological surveys under-estimated the percentage of HIV positives that are diagnosed by a relative factor of 12%. Research should be employed in other surveillance systems that benefit f

JOURNAL ARTICLE

Woods B, Rothery C, Anderson S-J, Eaton JW, Revill P, Hallett TB, Claxton Ket al., Appraising the value of evidence generation activities: An HIV Modelling Study, BMJ Global Health, ISSN: 2059-7908

Introduction: The generation of robust evidence has been emphasised as a priority for global health. Evidence generation spansa wide range of activities including clinical trials, surveillance programmes, andhealth systemperformance measurement. As resources for health care and research are limited, the desirability of research expenditure should be assessed on the same basis as other health care resources, i.e. the health gains from researchmust be expected to exceed the health opportunity costs imposed as funds are diverted to research rather than service provision. Methods: We developed atransmission and costing model to examine the impact of generating additional evidence to reduce uncertaintieson the evolution of ageneralised HIV epidemic in Zambia.Results: We demonstrate three important points. Firstly, we can quantify the value of additional evidence in terms of the health gain it is expected to generate. Secondly, we can quantify the health opportunity cost imposedby research expenditure. Thirdly, the value of evidence generation depends on thebudgetarypolicies in placefor managingHIV resourcesunder uncertainty. Generating evidence to reduce uncertainty is particularly valuablewhen decisionmakers are requiredto strictly adhereto expenditure plansand when transfers of funds across geographies/programmesare restricted.Conclusion: Better evidence can lead to health improvementsin the same way as direct delivery of health care. Quantitative appraisals of evidence generation activities are importantand should reflect the impact of improved evidence onpopulation health, evidence generationcosts, and budgetary policiesin place.

JOURNAL ARTICLE

Eaton J, Grebe E, Baumler P, McIntosh A, Ongarello S, Welte A, Kassangee R, Brand H, van Schalkwyk C, Li Y, Daniel S, Asai Yet al., 2018, Incidence Estimation Tools (inctools)

Tools for estimating incidence from biomarker data in cross-sectional surveys, and for calibrating tests for recent infection. Implements and extends the method of Kassanjee et al. (2012) doi:10.1097/EDE.0b013e3182576c07.

SOFTWARE

Marston M, Zaba B, Eaton J, 2018, Relative patterns of sexual activity and fertility among HIV positive and negative women – evidence from 46 DHS, PLoS ONE, Vol: 13, ISSN: 1932-6203

ObjectivesProjections of fertility of HIV positive women as ART scales up are needed to plan prevention of mother-to-child transmission (PMTCT) services. We describe differences in exposure to pregnancy between HIV positive and HIV negative women by age, region and national ART coverage to evaluate the extent to which behavioural differences explain lower fertility among HIV positive women and assess whether exposure to pregnancy has changed with antiretroviral treatment (ART) scale-up.MethodsWe analysed 46 nationally representative household surveys in sub-Saharan Africa conducted between 2003 and 2015 to estimate risk of exposure to recent sex and pregnancy of HIV positive and HIV negative women by age using a log binomial model. We tested for regional and urban/rural differences and associations with national ART coverage. We estimated an adjusted fertility rate ratio of HIV positive to HIV negative women adjusting for differences in exposure to pregnancy.ResultsExposure to pregnancy differs significantly between HIV positive and negative women by age, modified by region. Younger HIV positive women have a higher exposure to pregnancy than HIV negative women and the opposite is true at older ages. The switch occurs at 25–29 for rural women and 30–34 for urban women. There was no evidence that exposure to pregnancy of HIV positive women have changed as national ART coverage increased. The inferred rate of fecundity of HIV positive women when adjusted for differences in exposure to pregnancy were lower than unadjusted fertility rate ratios in women aged 20–29 and 20–24 in urban and rural areas respectively varying between 0.6 and 0.9 over regions.DiscussionThe direct effects of HIV on fertility are broadly similar across ages, while the dramatic age gradient that has frequently been observed is largely attributable to variation in relative sexual exposure by age.

JOURNAL ARTICLE

Tlhajoane M, Masoka T, Mpandaguta E, Rhead R, Church K, Wringe A, Kadzura N, Arinaminpathy N, Nyamukapa C, Schur N, Mugurungi O, Skovdal M, Eaton J, Gregson Set al., 2018, A longitudinal review of national HIV policy and progress made in health facility implementation in eastern Zimbabwe, Health Research Policy and Systems, Vol: 16, ISSN: 1478-4505

BackgroundIn recent years, WHO has made major changes to its guidance on the provision of HIV care and treatment services. We conducted a longitudinal study from 2013 to 2015 to establish how these changes have been translated into national policy in Zimbabwe and to measure progress in implementation within local health facilities.MethodsNational HIV programme policy guidelines published between 2003 and 2013 (n = 9) and 2014 and 2015 (n = 5) were reviewed to assess adoption of WHO recommendations on HIV testing services, prevention of mother-to-child transmission (PMTCT) of HIV, and provision of antiretroviral therapy (ART). Changes in local implementation of these policies over time were measured in two rounds of a survey conducted at 36 health facilities in Eastern Zimbabwe in 2013 and 2015.ResultsHigh levels of adoption of WHO guidance into national policy were recorded, including adoption of new recommendations made in 2013–2015 to introduce PMTCT Option B+ and to increase the threshold for ART initiation from CD4 ≤ 350 cells/mm3 to ≤ 500 cells/mm3. New strategies to implement national HIV policies were introduced such as the decentralisation of ART services from hospitals to clinics and task-shifting of care from doctors to nurses. The proportions of health facilities offering free HIV testing and counselling, PMTCT (including Option B+) and ART services increased substantially from 2013 to 2015, despite reductions in numbers of health workers. Provision of provider-initiated HIV testing remained consistently high. At least one test-kit stock-out in the prior year was reported in most facilities (2013: 69%; 2015: 61%; p = 0.44). Stock-outs of first-line ART and prophylactic drugs for opportunistic infections remained low. Repeat testing for HIV-negative individuals within 3 months decreased (2013: 97%; 2015: 72%; p = 0.01). Laboratory testing remained low across both surve

JOURNAL ARTICLE

Phillips A, Cambiano V, Bansi-Matharu L, Nakagawa F, Wilson D, Jani I, Apollo T, Sculpher M, Hallett T, Kerr C, van Oosterhout J, Eaton J, Estill J, Williams B, Doi N, Cowan F, Keiser O, Ford D, Hatzold K, Barnabas R, Ayles H, Meyer-Rath G, Nelson L, Johnson C, Baggaley R, Fakoya A, Jahn A, Revill Pet al., 2018, Cost-of-testing-per-new-HIV-diagnosis as a metric for monitoring cost-effectiveness of testing programmes in low income settings in Southern Africa: health economic modelling analysis, Publisher: JOHN WILEY & SONS LTD, Pages: 27-28, ISSN: 1758-2652

CONFERENCE PAPER

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

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

JOURNAL ARTICLE

Tlhajoane M, Eaton JW, Takaruza A, Rhead R, Maswera R, Schur N, Sherr L, Nyamukapa C, Gregson Set al., 2018, Prevalence and associations of psychological distress, HIV infection and HIV care service utilization in East Zimbabwe, AIDS and Behavior, Vol: 22, Pages: 1485-1495, ISSN: 1090-7165

The correlation between mental health and sexual risk behaviours for HIV infection remains largely unknown in low and middle income settings. The present study determined the prevalence of psychological distress (PD) in a sub-Saharan African population with a generalized HIV epidemic, and investigated associations with HIV acquisition risk and uptake of HIV services using data from a cross-sectional survey of 13,252 adults. PD was measured using the Shona Symptom Questionnaire. Logistic regression was used to measure associations between PD and hypothesized covariates. The prevalence of PD was 4.5% (95% CI 3.9-5.1%) among men, and 12.9% (95% CI 12.2-13.6%) among women. PD was associated with sexual risk behaviours for HIV infection and HIV-infected individuals were more likely to suffer from PD. Amongst those initiated on anti-retroviral therapy, individuals with PD were less likely to adhere to treatment (91 vs. 96%; age- and site-type-adjusted odds ratio = 0.38; 95% CI 0.15, 0.99). Integrated HIV and mental health services may enhance HIV care and treatment outcomes in high HIV-prevalence populations in sub-Saharan Africa.

JOURNAL ARTICLE

Kim S-H, Eaton JW, Davies B, Ward Het al., 2017, Patterns in chlamydia detection rate in young adults aged 15–24 years in England, 2012–15: longitudinal analysis of routine data, Public Health Science 2017

BackgroundThe National Chlamydia Screening Programme (NCSP) in England recommends chlamydia testing for sexually active young adults (aged 15–24 years). The Public Health Outcomes Framework (PHOF) suggests that implementation and delivery of the NCSP should identify 2300 cases or more of chlamydia per 100 000 residents (15–24 years old). The commissioning of chlamydia screening moved to local authorities in 2013. We describe performance of local authorities against the PHOF chlamydia screening recommendation.MethodsWe used chlamydia test data from Public Health England (2012–15), index of multiple deprivation (2015) data from National Office of Statistics, and population data to describe the association between the proportion of local authorities achieving the PHOF chlamydia detection rate recommendation and deprivation at local authority level, adjusted for population size and proportion of tests performed in a genitourinary medicine setting.FindingsThe number of chlamydia tests performed within the NCSP declined by 17% (1 860 000 in 2012 to 1 538 000 in 2015) over the study period. The proportion of local authorities that achieved the PHOF chlamydia diagnosis rate recommendation fell 39% (from 23% [75/324] in 2012 to 14% [45/324] in 2015). Throughout the 4-year period, local authorities in the most-deprived quintile were more likely to attain the recommendation than were local authorities in the least-deprived quintile (adjusted odds ratio 10·6 (95% CI 3·0–37·9) in 2012, 15·9 (2·0–129·5) in 2015).InterpretationThere has been a reduction in the number of chlamydia tests performed within the NCSP and a larger reduction in the proportion of local authorities meeting the chlamydia diagnosis rate recommendation since 2012. This finding suggests that the decline in testing may disproportionately affect those most at risk of chlamydia infection. There are also marked inequalities in attainment of the

POSTER

Slaymaker E, McLean E, Wringe A, Calvert C, Marston M, Reniers G, Kabudula CW, Crampin A, Price A, Michael D, Urassa M, Kwaro D, Sewe M, Eaton JW, Rhead R, Nakiyingi-Miiro J, Lutalo T, Nabukalu D, Herbst K, Hosegood V, Zaba Bet al., 2017, The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA): Data on mortality, by HIV status and stage on the HIV care continuum, among the general population in seven longitudinal studies between 1989 and 2014, Gates Open Research, Vol: 1, Pages: 4-4, ISSN: 2572-4754

Timely progression of people living with HIV (PLHIV) from the point of infection through the pathway from diagnosis to treatment is important in ensuring effective care and treatment of HIV and preventing HIV-related deaths and onwards transmission of infection.  Reliable, population-based estimates of new infections are difficult to obtain for the generalised epidemics in sub-Saharan Africa.  Mortality data indicate disease burden and, if disaggregated along the continuum from diagnosis to treatment, can also reflect the coverage and quality of different HIV services.  Neither routine statistics nor observational clinical studies can estimate mortality prior to linkage to care nor following disengagement from care.  For this, population-based data are required. The Network for Analysing Longitudinal Population-based HIV/AIDS data on Africa brings together studies in Kenya, Malawi, South Africa, Tanzania, Uganda, and Zimbabwe.  Eight studies have the necessary data to estimate mortality by HIV status, and seven can estimate mortality at different stages of the HIV care continuum.  This data note describes a harmonised dataset containing anonymised individual-level information on survival by HIV status for adults aged 15 and above. Among PLHIV, the dataset provides information on survival during different periods: prior to diagnosis of infection; following diagnosis but before linkage to care; in pre-antiretroviral treatment (ART) care; in the first six months after ART initiation; among people continuously on ART for 6+ months; and among people who have ever interrupted ART.

JOURNAL ARTICLE

Marston M, Zaba B, Eaton JW, 2017, The relationship between HIV and fertility in the era of antiretroviral therapy in sub Saharan Africa – Evidence from 49 Demographic & Health Surveys, Tropical Medicine and International Health, Vol: 22, Pages: 1542-1550, ISSN: 1360-2276

ObjectivesTo describe regional differences in the relative fertility of HIV-positive vs. HIV-negative women and changes as antiretroviral treatment (ART) is scaled up, to improve estimates of predicted need for and coverage of prevention of mother-to-child transmission services at national and subnational levels.MethodsWe analysed 49 nationally representative household surveys in sub-Saharan Africa between 2003 and 2016 to estimate fertility rate ratios of HIV-positive and HIV-negative women by age using exponential regression and test for regional and urban/rural differences. We estimated the association between national ART coverage and the relationship between HIV and fertility.ResultsSignificant regional differences exist in HIV and fertility relationships, with less HIV-associated subfertility in Southern Africa. Age patterns of relative fertility are similar. HIV impact on fertility is weaker in urban than rural areas. For women below age 30, regional and urban/rural differences are largely explained by differences in age at sexual debut. Higher levels of national ART coverage were associated with slight attenuation of the relationship between HIV and fertility.ConclusionsRegional differences in HIV-associated subfertility and urban–rural differences in age patterns of relative fertility should be accounted for when predicting need for and coverage of PMTCT services at national and subnational level. Although HIV impacts on fertility are somewhat reduced at higher levels of national ART coverage, differences in fertility between HIV positive and negative remain, and fertility of women on ART should not be assumed to be the same as HIV-negative women. There were few data in recent years, when ART has reached high levels, and this relationship should continue to be assessed as further evidence becomes available.

JOURNAL ARTICLE

Reniers G, Blom S, Lieber J, Herbst AJ, Calvert C, Bor J, Barnighausen T, Zaba B, Li ZR, Clark SJ, Grant AD, Lessells R, Eaton JW, Hosegood Vet al., 2017, Tuberculosis mortality and the male survival deficit in rural South Africa: an observational community cohort study, PLoS ONE, Vol: 12, ISSN: 1932-6203

BackgroundWomen live on average five years longer than men, and the sex difference in longevity is typically lower in populations with high mortality. South Africa—a high mortality population with a large sex disparity—is an exception, but the causes of death that contribute to this difference are not well understood.MethodsUsing data from a demographic surveillance system in rural KwaZulu-Natal (2000–2014), we estimate differences between male and female adult life expectancy by HIV status. The contribution of causes of death to these life expectancy differences are computed with demographic decomposition techniques. Cause of death information comes from verbal autopsy interviews that are interpreted with the InSilicoVA tool.ResultsAdult women lived an average of 10.4 years (95% confidence Interval 9.0–11.6) longer than men. Sex differences in adult life expectancy were even larger when disaggregated by HIV status: 13.1 (95% confidence interval 10.7–15.3) and 11.2 (95% confidence interval 7.5–14.8) years among known HIV negatives and positives, respectively. Elevated male mortality from pulmonary tuberculosis (TB) and external injuries were responsible for 43% and 31% of the sex difference in life expectancy among the HIV negative population, and 81% and 16% of the difference among people living with HIV.ConclusionsThe sex differences in adult life expectancy in rural KwaZulu-Natal are exceptionally large, atypical for an African population, and largely driven by high male mortality from pulmonary TB and injuries. This is the case for both HIV positive and HIV negative men and women, signalling a need to improve the engagement of men with health services, irrespective of their HIV status.

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

Eaton JW, Hargreaves J, 2017, How will we get there? How will we know?, Lancet HIV, Vol: 4, Pages: e429-e430, ISSN: 2405-4704

Ending AIDS by 2030 is a monumental challenge. Tracking progress as incidence reaches lower levels could be just as challenging. In The Lancet HIV Sabin Nsanzimana and colleagues report progress and highlight the challenges that lie ahead on both fronts. The Rwanda HIV Incidence Survey enumerated a nationally representative sample of 13 728 HIV-negative adults in 2013, and followed up a remarkable 92% of participants 1 year later. The investigators detected 35 HIV seroconversions at follow-up. Two findings are especially noteworthy.

JOURNAL ARTICLE

Pufall E, Eaton JW, Robertson L, Mushati P, Nyamukapa C, Gregson Set al., 2017, Education, substance use, and HIV risk among orphaned adolescents in Eastern Zimbabwe, Vulnerable Children and Youth Studies, Vol: 12, Pages: 360-374, ISSN: 1745-0136

There is a growing interest in education as a means to reduce HIV infection in vulnerable children in sub-Saharan Africa; however, the mechanisms by which education reduces HIV infection remain uncertain. Substance use has been associated with high-risk sexual behaviour and could lie on the causal pathway between education and HIV risk. Therefore, we used multivariable regression to measure associations between: (i) orphanhood and substance use (alcohol, recreational drugs, and smoking), (ii) substance use and sexual risk behaviours, and (iii) school enrolment and substance use, in adolescents aged 15–19 years, in Eastern Zimbabwe. We found substance use to be low overall (6.4%, 3.2%, and 0.9% of males reported alcohol, drug, and cigarette use; <1% of females reported any substance use), but was more common in male maternal and double orphans than non-orphans. Substance use was positively associated with early sexual debut, number of sexual partners, and engaging in transactional sex, while school enrolment was associated with lower substance use in males. We conclude that education may reduce sexual risk behaviours and HIV infection rates among male adolescents in sub-Saharan Africa, in part, by reducing substance abuse.

JOURNAL ARTICLE

Schaefer R, Gregson S, Eaton JW, Mugurungi O, Rhead R, Takaruza A, Maswera R, Nyamukapa Cet al., 2017, Age-disparate relationships and HIV incidence in adolescent girls and young women: evidence from a general-population cohort in Zimbabwe, AIDS, Vol: 31, Pages: 1461-1470, ISSN: 0269-9370

Objective: Age-disparate sexual relationships with older men may drive high rates of HIV acquisition in young women in sub-Saharan Africa but evidence is limited. We investigate the association between age-disparate relationships and HIV incidence in Manicaland, Zimbabwe.Design: A general-population open-cohort study (six surveys) (1998-2013).Methods: 3746 young women aged 15-24 years participated in consecutive surveys and were HIV-negative at the beginning of inter-survey periods. Last sexual partner age difference and age-disparate relationships (inter-generational [≥10 years age difference] and intra-generational [5-9 years] versus age-homogeneous [0-4 years]) were tested for associations with HIV incidence in Cox regressions. A proximate determinants framework was used to explore factors possibly explaining variations in the contribution of age-disparate relationships to HIV incidence between populations and over time.Results: 126 HIV infections occurred over 8777 person-years (1.43 per 100 person-years; 95% confidence interval=1.17-1.68). 65% of women reported partner age differences of ≥5 years. Increasing partner age differences were associated with higher HIV incidence (adjusted hazard ratio [aHR]=1.05 [1.01-1.09]). Inter-generational relationships tended to increase HIV incidence (aHR=1.78 [0.96-3.29]) but not intra-generational relationships (aHR=0.91 [0.47-1.76]). Secondary education was associated with reductions in inter-generational relationships (adjusted odds ratio [aOR]=0.49 [0.36-0.68]). Inter-generational relationships were associated with partners having concurrent relationships (aOR=2.59 [1.81-3.70]) which tended to increase HIV incidence (aHR=1.74 [0.96-3.17]). Associations between age-disparity and HIV incidence did not change over time.Conclusions: Sexual relationships with older men expose young women to increased risk of HIV acquisition in Manicaland, which did not change over time, even with introduction of antiretroviral therapy.

JOURNAL ARTICLE

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.

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Eaton JW, Johnson CC, Gregson S, 2017, The cost of not re-testing: HIV misdiagnosis in the ART ‘test-and-offer’ era, Clinical Infectious Diseases, Vol: 65, Pages: 522-525, ISSN: 1537-6591

We compared estimated costs of retesting human immunodeficiency virus (HIV)-positive persons before antiretroviral therapy (ART) initiation to the costs of ART provision to misdiagnosed HIV-negative persons. Savings from averted unnecessary ART costs were greater than retesting costs within 1 year using assumptions representative of HIV testing performance in programmatic settings. Countries should implement re-testing before ART initiation.

JOURNAL ARTICLE

McRobie E, Wringe A, Nakiyingi-Miiro J, Kiweqewa F, Lutalo T, Nakigozi G, Todd J, Eaton JW, Zaba B, Church Ket al., 2017, HIV policy implementation in two health and demographic surveillance sites in Uganda: findings from a national policy review, health facility surveys, and key informant interviews, Implementation Science, Vol: 12, ISSN: 1748-5908

BackgroundSuccessful HIV testing, care and treatment policy implementation is essential for realising the reductions in morbidity and mortality those policies are designed to target. While adoption of new HIV policies is rapid, less is known about the facility-level implementation of new policies and the factors influencing this.MethodsWe assessed implementation of national policies about HIV testing, treatment and retention at health facilities serving two health and demographic surveillance sites (HDSS) (10 in Kyamulibwa, 14 in Rakai). Ugandan Ministry of Health HIV policy documents were reviewed in 2013, and pre-determined indicators were extracted relating to the content and nature of guidance on HIV service provision. Facility-level policy implementation was assessed via a structured questionnaire administered to in-charge staff from each health facility. Implementation of policies was classified as wide (≥75% facilities), partial (26–74% facilities) or minimal (≤25% facilities). Semi-structured interviews were conducted with key informants (policy-makers, implementers, researchers) to identify factors influencing implementation; data were analysed using the Framework Method of thematic analysis.ResultsMost policies were widely implemented in both HDSS (free testing, free antiretroviral treatment (ART), WHO first-line regimen as standard, Option B+). Both had notable implementation gaps for policies relating to retention on treatment (availability of nutritional supplements, support groups or isoniazid preventive therapy). Rakai implemented more policies relating to provision of antiretroviral treatment than Kyamulibwa and performed better on quality of care indicators, such as frequency of stock-outs. Factors facilitating implementation were donor investment and support, strong scientific evidence, low policy complexity, phased implementation and effective planning. Limited human resources, infrastructure and health management information systems w

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Silhol R, Gregson S, Nyamukapa C, Mhangara M, Dzangare J, Gonese E, Eaton JW, Case KK, Mahy M, Stover J, Mugurungi Oet al., 2017, Empirical validation of the UNAIDS Spectrum model for subnational HIV estimates: case-study of children and adults in Manicaland, Zimbabwe, AIDS, Vol: 31, Pages: S41-S50, ISSN: 0269-9370

Background: More cost-effective HIV control may be achieved by targeting geographical areas with high infection rates. The AIDS Impact model of Spectrum – used routinely to produce national HIV estimates – could provide the required subnational estimates but is rarely validated with empirical data, even at a national level.Design: The validity of the Spectrum model estimates were compared to empirical estimates.Methods: Antenatal surveillance and population survey data from a population HIV cohort study in Manicaland, east Zimbabwe, were input into Spectrum 5.441 to create a simulation representative of the cohort population. Model and empirical estimates were compared for key demographic and epidemiological outcomes. Alternative scenarios for data availability were examined and sensitivity analyses were conducted for model assumptions considered important for subnational estimates.Results: Spectrum estimates generally agreed with observed data but HIV incidence estimates were higher than empirical estimates while estimates of early age all-cause adult mortality were lower. Child HIV prevalence estimates matched well with the survey prevalence among children. Estimated paternal orphanhood was lower than empirical estimates. Including observations from earlier in the epidemic did not improve the HIV incidence model fit. Migration had little effect on observed discrepancies - possibly because the model ignores differences in HIV prevalence between migrants and residents.Conclusions: The Spectrum model, using subnational surveillance and population data, provided reasonable subnational estimates although some discrepancies were noted. Differences in HIV prevalence between migrants and residents may need to be captured in the model if applied to subnational epidemics.

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

Masquelier B, Eaton JW, Gerland P, Pelletier F, Mutai KKet al., 2017, Age patterns and sex ratios of adult mortality in countries with high HIV prevalence, AIDS, Vol: 31, Pages: S77-S85, ISSN: 0269-9370

Objective: To compare the 2016 United Nations Programme on HIV/AIDS (UNAIDS) modelled estimates of adult mortality in sub-Saharan Africa to empirical estimates.Design: Age-specific mortality rates were obtained from nationally representative sibling survival data, recent household deaths and vital registration, and directly compared with UNAIDS estimates. Orphanhood prevalence derived from UNAIDS mortality estimates was compared with survey and census reports on the survival of children's parents.Methods: Age-specific mortality rates for adults aged 15–59 years were calculated from Demographic and Health Surveys and deaths reported in censuses or vital registration, adjusted for underreporting, whenever possible. Proportions of orphans were extracted from censuses and surveys for children aged 5–9 years.Results: UNAIDS estimates were significantly higher than sibling mortality estimates, except among men in countries with very high HIV prevalence. There was a better agreement between rates based on household deaths or vital registration and model outputs. Sex ratios (M/F) of adult mortality were lower in UNAIDS estimates. The modelled orphan prevalence was significantly higher than in surveys and censuses, again with the exception of paternal orphans in countries with very high HIV prevalence. Ratios of paternal-to-maternal orphans were lower in the UNAIDS model than surveys and censuses. Among women, increases in mortality due to AIDS were more concentrated in the age range 25–50 years in model outputs, as compared with empirical estimates.Conclusion: Discrepancies in levels, sex ratios and age patterns of adult mortality between empirical and UNAIDS estimates call for additional data quality assessments and improvements in estimation methods.

JOURNAL ARTICLE

Eaton JW, Bao L, 2017, Accounting for nonsampling error in estimates of HIV epidemic trends from antenatal clinic sentinel surveillance, AIDS, Vol: 31, Pages: S61-S68, ISSN: 0269-9370

Objectives: The aim of the study was to propose and demonstrate an approach to allowadditional nonsampling uncertainty about HIV prevalence measured at antenatal clinicsentinel surveillance (ANC-SS) in model-based inferences about trends in HIV incidenceand prevalence.Design: Mathematical model fitted to surveillance data with Bayesian inference.Methods: We introduce a variance inflation parameter s2in fl that accounts for theuncertainty of nonsampling errors in ANC-SS prevalence. It is additive to the samplingerror variance. Three approaches are tested for estimating s2in fl using ANC-SS andhousehold survey data from 40 subnational regions in nine countries in sub-Saharan, asdefined in UNAIDS 2016 estimates. Methods were compared using in-sample fit andout-of-sample prediction of ANC-SS data, fit to household survey prevalence data, andthe computational implications.Results: Introducing the additional variance parameter s2in fl increased the error variancearound ANC-SS prevalence observations by a median of 2.7 times (interquartilerange 1.9–3.8). Using only sampling error in ANC-SS prevalence (s2in fl ¼ 0), coverageof 95% prediction intervals was 69% in out-of-sample prediction tests. This increased to90% after introducing the additional variance parameter s2in fl. The revised probabilisticmodel improved model fit to household survey prevalence and increased epidemicuncertainty intervals most during the early epidemic period before 2005. Estimatings2in fl did not increase the computational cost of model fitting.Conclusions: We recommend estimating nonsampling error in ANC-SS as anadditional parameter in Bayesian inference using the Estimation and Projection Packagemodel. This approach may prove useful for incorporating other data sources such asroutine prevalence from Prevention of mother-to-child transmission testing into futureepidemic estimates.

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