Timothy B. Hallett

Why large-scale climate indices seem to predict ecological processes better than local weather

Large-scale climatic indices such as the North Atlantic Oscillation are associated with population dynamics, variation in demographic rates and values of phenotypic traits in many species. Paradoxically, these large-scale indices can seem to be better predictors of ecological processes than local climate. Using detailed data from a population of Soay sheep, we show that high rainfall, high winds or low temperatures at any time during a 3-month period can cause mortality either immediately or lagged by a few days. Most measures of local climate used by ecologists fail to capture such complex associations between weather and ecological process, and this may help to explain why large-scale, seasonal indices of climate spanning several months can outperform local climatic factors. Furthermore, we show why an understanding of the mechanism by which climate influences population ecology is important. Through simulation we demonstrate that the timing of bad weather within a period of mortality can have an important modifying influence on intraspecific competition for food, revealing an interaction between climate and density dependence that the use of large-scale climatic indices or inappropriate local weather variables might obscure.

Towards an improved investment approach for an effective response to HIV/AIDS

Substantial changes are needed to achieve a more targeted and strategic approach to investment in the response to the HIV/AIDS epidemic that will yield long-term dividends. Until now, advocacy for resources has been done on the basis of a commodity approach that encouraged scaling up of numerous strategies in parallel, irrespective of their relative effects. We propose a strategic investment framework that is intended to support better management of national and international HIV/AIDS responses than exists with the present system. Our framework incorporates major efficiency gains through community mobilisation, synergies between programme elements, and benefits of the extension of antiretroviral therapy for prevention of HIV transmission. It proposes three categories of investment, consisting of six basic programmatic activities, interventions that create an enabling environment to achieve maximum effectiveness, and programmatic efforts in other health and development sectors related to HIV/AIDS. The yearly cost of achievement of universal access to HIV prevention, treatment, care, and support by 2015 is estimated at no less than US

Examining the promise of HIV elimination by 'test and treat' in hyperendemic settings.

22 billion. Implementation of the new investment framework would avert 12·2 million new HIV infections and 7·4 million deaths from AIDS between 2011 and 2020 compared with continuation of present approaches, and result in 29·4 million life-years gained. The framework is cost effective at

Declines in HIV prevalence can be associated with changing sexual behaviour in Uganda, urban Kenya, Zimbabwe, and urban Haiti

1060 per life-year gained, and the additional investment proposed would be largely offset from savings in treatment costs alone.

A decline in new HIV infections in South Africa: estimating HIV incidence from three national HIV surveys in 2002, 2005 and 2008.

Background:It has been suggested that a new strategy for HIV prevention, ‘Universal Test and Treat’, whereby everyone is tested for HIV once a year and treated immediately with antiretroviral therapy (ART) if they are infected, could ‘eliminate’ the epidemic and reduce ART costs in the long term. Methods:We investigated the impact of test-and-treat interventions under a variety of assumptions about the epidemic using a deterministic mathematical model. Results:Our model shows that such an intervention can substantially reduce HIV transmission, but that impact depends crucially on the epidemiological context; in some situations, less aggressive interventions achieve the same results, whereas in others, the proposed intervention reduces HIV by much less. It follows that testing every year and treating immediately is not necessarily the most cost-efficient strategy. We also show that a test-and-treat intervention that does not reach full implementation or coverage could, perversely, increase long-term ART costs. Conclusion:Interventions that prevent new infections through ART scale-up may hold substantial promise. However, as plans move forward, careful consideration should be given to the nature of the epidemic and the potential for perverse outcomes.

Future challenges for clinical care of an ageing population infected with HIV: a modelling study

Objective: To determine whether observed changes in HIV prevalence in countries with generalised HIV epidemics are associated with changes in sexual risk behaviour. Methods: A mathematical model was developed to explore the relation between prevalence recorded at antenatal clinics (ANCs) and the pattern of incidence of infection throughout the population. To create a null model a range of assumptions about sexual behaviour, natural history of infection, and sampling biases in ANC populations were explored to determine which factors maximised declines in prevalence in the absence of behaviour change. Modelled prevalence, where possible based on locally collected behavioural data, was compared with the observed prevalence data in urban Haiti, urban Kenya, urban Cote d’Ivoire, Malawi, Zimbabwe, Rwanda, Uganda, and urban Ethiopia. Results: Recent downturns in prevalence observed in urban Kenya, Zimbabwe, and urban Haiti, like Uganda before them, could only be replicated in the model through reductions in risk associated with changes in behaviour. In contrast, prevalence trends in urban Cote d’Ivoire, Malawi, urban Ethiopia, and Rwanda show no signs of changed sexual behaviour. Conclusions: Changes in patterns of HIV prevalence in urban Kenya, Zimbabwe, and urban Haiti are quite recent and caution is required because of doubts over the accuracy and representativeness of these estimates. Nonetheless, the observed changes are consistent with behaviour change and not the natural course of the HIV epidemic.

Understanding the impact of male circumcision interventions on the spread of HIV in southern Africa.

Background Three national HIV household surveys were conducted in South Africa, in 2002, 2005 and 2008. A novelty of the 2008 survey was the addition of serological testing to ascertain antiretroviral treatment (ART) use. Methods and Principal Findings We used a validated mathematical method to estimate the rate of new HIV infections (HIV incidence) in South Africa using nationally representative HIV prevalence data collected in 2002, 2005 and 2008. The observed HIV prevalence levels in 2008 were adjusted for the effect of antiretroviral treatment on survival. The estimated “excess” HIV prevalence due to ART in 2008 was highest among women 25 years and older and among men 30 years and older. In the period 2002–2005, the HIV incidence rate among men and women aged 15–49 years was estimated to be 2.0 new infections each year per 100 susceptible individuals (/100pyar) (uncertainty range: 1.2–3.0/100pyar). The highest incidence rate was among 15–24 year-old women, at 5.5/100pyar (4.5–6.5). In the period 2005–2008, incidence among men and women aged 15–49 was estimated to be 1.3/100 (0.6–2.5/100pyar), although the change from 2002–2005 was not statistically significant. However, the incidence rate among young women aged 15–24 declined by 60% in the same period, to 2.2/100pyar, and this change was statistically significant. There is evidence from the surveys of significant increases in condom use and awareness of HIV status, especially among youth. Conclusions Our analysis demonstrates how serial measures of HIV prevalence obtained in population-based surveys can be used to estimate national HIV incidence rates. We also show the need to determine the impact of ART on observed HIV prevalence levels. The estimation of HIV incidence and ART exposure is crucial to disentangle the concurrent impact of prevention and treatment programs on HIV prevalence.

Mathematical models in the evaluation of health programmes

Summary Background The population infected with HIV is getting older and these people will increasingly develop age-related non-communicable diseases (NCDs). We aimed to quantify the scale of the change and the implications for HIV care in the Netherlands in the future. Methods We constructed an individual-based model of the ageing HIV-infected population, which followed patients on HIV treatment as they age, develop NCDs—including cardiovascular disease (hypertension, hypercholesterolaemia, myocardial infarctions, and strokes), diabetes, chronic kidney disease, osteoporosis, and non-AIDS malignancies—and start co-medication for these diseases. The model was parameterised by use of data for 10 278 patients from the national Dutch ATHENA cohort between 1996 and 2010. We made projections up to 2030. Findings Our model suggests that the median age of HIV-infected patients on combination antiretroviral therapy (ART) will increase from 43·9 years in 2010 to 56·6 in 2030, with the proportion of HIV-infected patients aged 50 years or older increasing from 28% in 2010 to 73% in 2030. In 2030, we predict that 84% of HIV-infected patients will have at least one NCD, up from 29% in 2010, with 28% of HIV-infected patients in 2030 having three or more NCDs. 54% of HIV-infected patients will be prescribed co-medications in 2030, compared with 13% in 2010, with 20% taking three or more co-medications. Most of this change will be driven by increasing prevalence of cardiovascular disease and associated drugs. Because of contraindications and drug–drug interactions, in 2030, 40% of patients could have complications with the currently recommended first-line HIV regimens. Interpretation The profile of patients in the Netherlands infected with HIV is changing, with increasing numbers of older patients with multiple morbidities. These changes mean that, in the near future, HIV care will increasingly need to draw on a wide range of medical disciplines, in addition to evidence-based screening and monitoring protocols to ensure continued high-quality care. These findings are based on a large dataset of HIV-infected patients in the Netherlands, but we believe that the overall patterns will be repeated elsewhere in Europe and North America. The implications of such a trend for care of HIV-infected patients in high-burden countries in Africa could present a particular challenge. Funding Medical Research Council, Bill & Melinda Gates Foundation, Rush Foundation, and Netherlands Ministry of Health, Welfare and Sport.

Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

Background Three randomised controlled trials have clearly shown that circumcision of adult men reduces the chance that they acquire HIV infection. However, the potential impact of circumcision programmes – either alone or in combination with other established approaches – is not known and no further field trials are planned. We have used a mathematical model, parameterised using existing trial findings, to understand and predict the impact of circumcision programmes at the population level. Findings Our results indicate that circumcision will lead to reductions in incidence for women and uncircumcised men, as well as those circumcised, but that even the most effective intervention is unlikely to completely stem the spread of the virus. Without additional interventions, HIV incidence could eventually be reduced by 25–35%, depending on the level of coverage achieved and whether onward transmission from circumcised men is also reduced. However, circumcision interventions can act synergistically with other types of prevention programmes, and if efforts to change behaviour are increased in parallel with the scale-up of circumcision services, then dramatic reductions in HIV incidence could be achieved. In the long-term, this could lead to reduced AIDS deaths and less need for anti-retroviral therapy. Any increases in risk behaviours following circumcision , i.e. ‘risk compensation’, could offset some of the potential benefit of the intervention, especially for women, but only very large increases would lead to more infections overall. Conclusions Circumcision will not be the silver bullet to prevent HIV transmission, but interventions could help to substantially protect men and women from infection, especially in combination with other approaches.

A Surprising Prevention Success: Why Did the HIV Epidemic Decline in Zimbabwe?

Modelling is valuable in the planning and evaluation of interventions, especially when a controlled trial is ethically or logistically impossible. Models are often used to calculate the expected course of events in the absence of more formal assessments. They are also used to derive estimates of rare or future events from recorded intermediate points. When developing models, decisions are needed about the appropriate level of complexity to be represented and about model structure and assumptions. The degree of rigor in model development and assessment can vary greatly, and there is a danger that existing beliefs inappropriately influence judgments about model assumptions and results.