Inferring HIV incidence trends and transmission dynamics with a spatio-temporal HIV epidemic model

Reliable estimation of spatio-temporal trends in population-level HIV incidence is becoming an increasingly critical component of HIV prevention policy-making. However, direct measurement is nearly impossible. Current, widely used models infer incidence from survey and surveillance seroprevalence data, but they require unrealistic assumptions about spatial independence across spatial units. In this study, we present an epidemic model of HIV that explicitly simulates the spatial dynamics of HIV over many small, interacting areal units. By integrating all available population-level data, we are able to infer not only spatio-temporally varying incidence, but also ART initiation rates and patient counts. Our study illustrates the feasibility of applying compartmental models to larger inferential problems than those to which they are typically applied, as well as the value of data fusion approaches to infectious disease modeling.Comment: 28 pages, 9 figures, submitted to Epidemics

How will we get there? How will we know?

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

Impact of ART on the fertility of HIV-positive women in sub-Saharan Africa.

OBJECTIVE: Understanding the fertility of HIV-positive women is critical to estimating HIV epidemic trends from surveillance data and to planning resource needs and coverage of prevention of mother-to-child transmission services in sub-Saharan Africa. In the light of the considerable scale-up in antiretroviral therapy (ART) coverage over the last decade, we conducted a systematic review of the impact of ART on the fertility outcomes of HIV-positive women. METHODS: We searched Medline, Embase, Popline, PubMed and African Index Medicus. Studies were included if they were conducted in sub-Saharan Africa and provided estimates of fertility outcomes (live births or pregnancies) among women on ART relative to a comparison group. RESULTS: Of 2070 unique references, 18 published papers met all eligibility criteria. Comparisons fell into four categories: fertility of HIV-positive women relative to HIV-negative women; fertility of HIV-positive women on ART compared to those not yet on ART; fertility differences by duration on ART; and temporal trends in fertility among HIV-positive women. Evidence indicates that fertility increases after approximately the first year on ART and that while the fertility deficit of HIV-positive women is shrinking, their fertility remains below that of HIV-negative women. These findings, however, were based on limited data mostly during the period 2005-2010 when ART scaled up. CONCLUSIONS: Existing data are insufficient to characterise how ART has affected the fertility of HIV-positive women in sub-Saharan Africa. Improving evidence about fertility among women on ART is an urgent priority for planning HIV resource needs and understanding HIV epidemic trends. Alternative data sources such as antenatal clinic data, general population cohorts and population-based surveys can be harnessed to understand the issue

Spillover HIV prevention effects of a cash transfer trial in East Zimbabwe: evidence from a cluster-randomised trial and general-population survey

Background: Benefits of cash transfers (CTs) for HIV prevention have been demonstrated largely in purposively designed trials, commonly focusing on young women. It is less clear if CT interventions not designed for HIV prevention can have HIV-specific effects, including adverse effects. The cluster-randomised Manicaland Cash Transfer Trial (2010–11) evaluated effects of CTs on children’s (2–17 years) development in eastern Zimbabwe. We evaluated whether this CT intervention with no HIV-specific objectives had unintended HIV prevention spillover effects (externalities). Methods: Data on 2909 individuals (15–54 years) living in trial households were taken from a general-population survey, conducted simultaneously in the same communities as the Manicaland Trial. Average treatment effects (ATEs) of CTs on sexual behaviour (any recent sex, condom use, multiple partners) and secondary outcomes (mental distress, school enrolment, and alcohol/cigarette/drug consumption) were estimated using mixed-effects logistic regressions (random effects for study site and intervention cluster), by sex and age group (15–29; 30–54 years). Outcomes were also evaluated with a larger synthetic comparison group created through propensity score matching. Results: CTs did not affect sexual debut but reduced having any recent sex (past 30 days) among young males (ATE: − 11.7 percentage points [PP] [95% confidence interval: -26.0PP, 2.61PP]) and females (− 5.68PP [− 15.7PP, 4.34PP]), with similar but less uncertain estimates when compared against the synthetic comparison group (males: -9.68PP [− 13.1PP, − 6.30PP]; females: -8.77PP [− 16.3PP, − 1.23PP]). There were no effects among older individuals. Young (but not older) males receiving CTs reported increased multiple partnerships (8.49PP [− 5.40PP, 22.4PP]; synthetic comparison: 10.3PP (1.27PP, 19.2PP). No impact on alcohol, cigarette, or drug consumption was found. There are indications that CTs reduced psychological distress among young people, although impacts were small. CTs increased school enrolment in males (11.5PP [3.05PP, 19.9PP]). Analyses with the synthetic comparison group (but not the original control group) further indicated increased school enrolment among females (5.50PP [1.62PP, 9.37PP]) and condom use among younger and older women receiving CTs (9.38PP [5.90PP, 12.9PP]; 5.95PP [1.46PP, 10.4PP]). Conclusions: Non-HIV-prevention CT interventions can have HIV prevention outcomes, including reduced sexual activity among young people and increased multiple partnerships among young men. No effects on sexual debut or alcohol, cigarette, or drug consumption were observed. A broad approach is necessary to evaluate CT interventions to capture unintended outcomes, particularly in economic evaluations. Trial registration: ClinicalTrials.gov, NCT00966849. Registered August 27, 2009

The impact of HIV on children's education in eastern Zimbabwe

Little is known about how HIV impacts directly and indirectly on receiving, or particularly succeeding in, education in sub-Saharan Africa. To address this gap, we used multivariable logistic regression to determine the correlation between education outcomes in youth (aged 15-24) (being in the correct grade-for-age, primary school completion and having at least five "O" level passes) and being HIV-positive; having an HIV-positive parent; being a young carer; or being a maternal, paternal or double orphan, in five rounds (1998-2011) of a general population survey from eastern Zimbabwe. The fifth survey round (2009-2011) included data on children aged 6-17, which were analysed for the impacts of the above risk factors on regular attendance in primary and secondary schools and being in the correct grade-for-age. For data pooled over all rounds, being HIV-positive had no association with primary school completion, "O" level passes, or being in the correct grade-for-age in adolescents aged 16-17 years. Additionally, HIV status had no significant association with any education outcomes in children aged 6-17 surveyed in 2009-2011. In 2009-2011, being a young carer was associated with lower attendance in secondary school (69% vs. 85%, AOR: 0.44; p=0.02), whilst being a maternal (75% vs. 83%, AOR: 0.67; p<0.01), paternal (76% vs. 83%, AOR: 0.67; p=0.02) or double (75% vs. 83%, AOR: 0.68; p=0.02) orphan was associated with decreased odds of being in the correct grade-for-age. All forms of orphanhood also significantly decreased the odds of primary school completion in youths surveyed from 1998 to 2011 (all p<0.01). We found no evidence that HIV status affects education but further evidence that orphans do experience worse education outcomes than other children. Combination approaches that provide incentives for children to attend school and equip schools with tools to support vulnerable children may be most effective in improving education outcomes and should be developed and evaluated

The contribution of schools to supporting the well being of children affected by HIV in eastern Zimbabwe

OBJECTIVES: Schools are often cited as a source of support for orphans and children affected by HIV/AIDS in populations experiencing generalized HIV epidemics and severe poverty. Here we investigate the success of schools at including and supporting the well being of vulnerable children in rural Zimbabwe. DESIGN: Data from a cross-sectional household survey of 4577 children (aged 6–17 years), conducted between 2009 and 2011, were linked to data on the characteristics of 28 primary schools and 18 secondary schools from a parallel monitoring and evaluation facility survey. METHODS: We construct two measures of school quality (one general and one HIV-specific) and use multivariable regression to test whether these were associated with improved educational outcomes and well being for vulnerable children. RESULTS: School quality was not associated with primary or secondary school attendance, but was associated with children’s being in the correct grade for age [adjusted odds ratio 2.0, 95% confidence interval (CI) 1.2–3.5, P = 0.01]. General and HIV-specific school quality had significant positive effects on well being in the primary school-age children (coefficient 5.1, 95% CI 2.4–7.7, P < 0.01 and coefficient 3.0, 95% CI 0.4–5.6, P = 0.02, respectively), but not in the secondary school-age children (P > 0.2). There was no evidence that school quality provided an additional benefit to the well being of vulnerable children. Community HIV prevalence was negatively associated with well being in the secondary school-age children (coefficient −0.7, 95% CI −1.3 to −0.1, P = 0.03). CONCLUSIONS: General and HIV-specific school quality may enhance the well being of primary school-age children in eastern Zimbabwe. Local community context also plays an important role in child well being

The effects of HIV on fertility by infection duration: evidence from African population cohorts before antiretroviral treatment availability.

OBJECTIVES: To estimate the relationship between HIV natural history and fertility by duration of infection in east and southern Africa before the availability of antiretroviral therapy and assess potential biases in estimates of age-specific subfertility when using retrospective birth histories in cross-sectional studies. DESIGN: Pooled analysis of prospective population-based HIV cohort studies in Masaka (Uganda), Kisesa (Tanzania) and Manicaland (Zimbabwe). METHODS: Women aged 15-49 years who had ever tested for HIV were included. Analyses were censored at antiretroviral treatment roll-out. Fertility rate ratios were calculated to see the relationship of duration of HIV infection on fertility, adjusting for background characteristics. Survivorship and misclassification biases on age-specific subfertility estimates from cross-sectional surveys were estimated by reclassifying person-time from the cohort data to simulate cross-sectional surveys and comparing fertility rate ratios with true cohort results. RESULTS: HIV-negative and HIV-positive women contributed 15 440 births and 86 320 person-years; and 1236 births and 11 240 000 person-years, respectively, to the final dataset. Adjusting for age, study site and calendar year, each additional year since HIV seroconversion was associated with a 0.02 (95% confidence interval 0.01-0.03) relative decrease in fertility for HIV-positive women. Survivorship and misclassification biases in simulated retrospective birth histories resulted in modest underestimates of subfertility by 2-5% for age groups 20-39 years. CONCLUSION: Longer duration of infection is associated with greater relative fertility reduction for HIV-positive women. This should be considered when creating estimates for HIV prevalence among pregnant women and prevention of mother-to-child transmission need over the course of the HIV epidemic and antiretroviral treatment scale up

Effects of unconditional and conditional cash transfers on child health and development in Zimbabwe: a cluster-randomised trial

SummaryBackgroundCash-transfer programmes can improve the wellbeing of vulnerable children, but few studies have rigorously assessed their effectiveness in sub-Saharan Africa. We investigated the effects of unconditional cash transfers (UCTs) and conditional cash transfers (CCTs) on birth registration, vaccination uptake, and school attendance in children in Zimbabwe.MethodsWe did a matched, cluster-randomised controlled trial in ten sites in Manicaland, Zimbabwe. We divided each study site into three clusters. After a baseline survey between July, and September, 2009, clusters in each site were randomly assigned to UCT, CCT, or control, by drawing of lots from a hat. Eligible households contained children younger than 18 years and satisfied at least one other criteria: head of household was younger than 18 years; household cared for at least one orphan younger than 18 years, a disabled person, or an individual who was chronically ill; or household was in poorest wealth quintile. Between January, 2010, and January, 2011, households in UCT clusters collected payments every 2 months. Households in CCT clusters could receive the same amount but were monitored for compliance with several conditions related to child wellbeing. Eligible households in all clusters, including control clusters, had access to parenting skills classes and received maize seed and fertiliser in December, 2009, and August, 2010. Households and individuals delivering the intervention were not masked, but data analysts were. The primary endpoints were proportion of children younger than 5 years with a birth certificate, proportion younger than 5 years with up-to-date vaccinations, and proportion aged 6–12 years attending school at least 80% of the time. This trial is registered with ClinicalTrials.gov, number NCT00966849.Findings1199 eligible households were allocated to the control group, 1525 to the UCT group, and 1319 to the CCT group. Compared with control clusters, the proportion of children aged 0–4 years with birth certificates had increased by 1·5% (95% CI −7·1 to 10·1) in the UCT group and by 16·4% (7·8–25·0) in the CCT group by the end of the intervention period. The proportions of children aged 0–4 years with complete vaccination records was 3·1% (−3·8 to 9·9) greater in the UCT group and 1·8% (−5·0 to 8·7) greater in the CCT group than in the control group. The proportions of children aged 6–12 years who attended school at least 80% of the time was 7·2% (0·8–13·7) higher in the UCT group and 7·6% (1·2–14·1) in the CCT group than in the control group.InterpretationOur results support strategies to integrate cash transfers into social welfare programming in sub-Saharan Africa, but further evidence is needed for the comparative effectiveness of UCT and CCT programmes in this region.FundingWellcome Trust, the World Bank through the Partnership for Child Development, and the Programme of Support for the Zimbabwe National Action Plan for Orphans and Vulnerable Children

Household-based cash transfer targeting strategies in Zimbabwe: are we reaching the most vulnerable children?

Census data, collected in July 2009, from 27,672 children were used to compare the effectiveness, coverage and efficacy of three household-based methods for targeting cash transfers to vulnerable children in eastern Zimbabwe: targeting the poorest households using a wealth index; targeting HIVaffected households using socio-demographic information (households caring for orphans, chronicallyill or disabled members; child-headed households); and targeting labour-constrained households using dependency ratios. All three methods failed to identify large numbers of children with poor social and educational outcomes. The wealth index approach was the most efficient at reaching children with poor outcomes whilst socio-demographic targeting reached more vulnerable children but was less efficient.publishedVersio

Appraising the value of evidence generation activities : an HIV modelling study

Introduction: The generation of robust evidence has been emphasised as a priority for global health. Evidence generation spans a wide range of activities including clinical trials, surveillance programmes and health system performance measurement. As resources for healthcare and research are limited, the desirability of research expenditure should be assessed on the same basis as other healthcare resources, that is, the health gains from research must be expected to exceed the health opportunity costs imposed as funds are diverted to research rather than service provision. Methods: We developed a transmission and costing model to examine the impact of generating additional evidence to reduce uncertainties on the evolution of a generalised HIV epidemic in Zambia. Results: We demonstrate three important points. First, we can quantify the value of additional evidence in terms of the health gain it is expected to generate. Second, we can quantify the health opportunity cost imposed by research expenditure. Third, the value of evidence generation depends on the budgetary policies in place for managing HIV resources under uncertainty. Generating evidence to reduce uncertainty is particularly valuable when decision makers are required to strictly adhere to expenditure plans and when transfers of funds across geographies/programmes are restricted. Conclusion: Better evidence can lead to health improvements in the same way as direct delivery of healthcare. Quantitative appraisals of evidence generation activities are important and should reflect the impact of improved evidence on population health, evidence generation costs and budgetary policies in place