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Lay summary
Background: The HIV/AIDS pandemic is a public health emergency in many low-income and middle-income countries. There were an estimated 33.3 million people living with HIV at the end of 2009, with 11.3 million living in Southern Africa. Since 2004 efforts by governments and others have resulted in a massive scale-up of highly active antiretroviral combination therapy (ART): at the end of 2009, 3.9 million people were reported to be receiving antiretroviral therapy in sub-Saharan Africa. The impact of the scale-up of ART on the incidence of new infections in Africa is hotly debated but unclear at present. We would like to address this question by building a mathematical transmission model based on the International epidemiological Databases in Southern Africa (IeDEA-SA). Rationale: The concept of ‘treatment as prevention’ or ‘test-and-treat’ is topical and a better understanding of the place of ART in prevention is urgently needed. The 2010 treatment guidelines of the World Health Organization (WHO) recommend earlier initiation of ART (when CD4 cell counts fall to 350 cells/μl or lower, rather than 200 cells/μl), which means that many more people living with HIV have become eligible for ART. Previous models of ART in low-income settings focussed on clinical outcomes without considering its impact on HIV transmission, or on HIV transmission without modelling the scale-up of ART in resource-constrained settings. There is an urgent need for more comprehensive models that consider the realities of ART in sub-Saharan Africa, including the high rate of loss to follow-up, the lack of viral load (VL) monitoring, treatment interruptions and stock outs, and the incidence of treatment failure. Objectives: We aim to develop an individual-based, comprehensive mathematical model of the impact of ART on HIV transmission in Southern Africa, based on the data from IeDEA-SA. In particular, we will explore the role of routine VL monitoring and study the impact on HIV transmission at the population level of the new WHO guidelines.   Methods: IeDEA-SA is a large collaborative network of HIV treatment sites in Southern Africa, with coordinating centres at the Universities of Bern, Switzerland and Cape Town, South Africa. The current database includes 288,015 adults (251,759 on ART) and 30,470 children (24,277 on ART) in 23 programmes in 6 countries (Botswana, Malawi, Mozambique, South Africa and Zambia, Zimbabwe). All participating clinics collect socio-demographic, clinical, laboratory, and pharmacological data at the individual patient level, using an agreed protocol and database structure. Patients are followed up 3 to 6 monthly. VL is regularly measured in South Africa and Botswana. Outcomes include changes in virological and immunological failure of ART, mortality and loss to follow-up. We will use the IeDEA-SA data to parameterize the model, and review published transmission models and the literature to extract data on sexual behaviour (not collected in IeDEA) and partner change. We will adapt the individual-based ART model developed at ISPM Bern to include components relevant to HIV transmission (pre-ART period, individual VL and CD4 trajectories etc.), integrate the ART model into the transmission model, explore model uncertainty and validate the model, and test pre-specified hypotheses. Significance: This will be the first HIV transmission model that incorporates detailed information that reflects the realities of ART in Southern Africa. The model will predict the future course of the epidemic in the ART era under different scenarios and aid decision making. Mathematical modelling complements randomized controlled trial and epidemiological research: it is time- and cost-saving and allows testing a wealth of different strategies. The project provides an ideal environment for a PhD student and will strengthen existing collaborations with renowned mathematical modellers in the field of HIV.

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Last update: 21.02.2013

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Number	Title	Start	Funding scheme

Background: The HIV/AIDS pandemic is a public health emergency in many low-income and middle-income countries. There were an estimated 33.3 million people living with HIV at the end of 2009, with 11.3 million living in Southern Africa. Since 2004 efforts by governments and others have resulted in a massive scale-up of highly active antiretroviral combination therapy (ART): at the end of 2009, 3.9 million people were reported to be receiving antiretroviral therapy in sub-Saharan Africa. The impact of the scale-up of ART on the incidence of new infections in Africa is hotly debated but unclear at present. We would like to address this question by building a mathematical transmission model based on the International epidemiological Databases in Southern Africa (IeDEA-SA). Rationale: The concept of ‘treatment as prevention’ or ‘test-and-treat’ is topical and a better understanding of the place of ART in prevention is urgently needed. The 2010 treatment guidelines of the World Health Organization (WHO) recommend earlier initiation of ART (when CD4 cell counts fall to 350 cells/µl or lower, rather than 200 cells/µl), which means that many more people living with HIV have become eligible for ART. Previous models of ART in low-income settings focussed on clinical outcomes without considering its impact on HIV transmission, or on HIV transmission without modelling the scale-up of ART in resource-constrained settings. There is an urgent need for more comprehensive models that consider the realities of ART in sub-Saharan Africa, including the high rate of loss to follow-up, the lack of viral load (VL) monitoring, treatment interruptions and stock outs, and the incidence of treatment failure.Objectives: We aim to develop an individual-based, comprehensive mathematical model of the impact of ART on HIV transmission in Southern Africa, based on the data from IeDEA-SA. In particular, we will explore the role of routine VL monitoring and study the impact on HIV transmission at the population level of the new WHO guidelines.Methods: IeDEA-SA is a large collaborative network of HIV treatment sites in Southern Africa, with coordinating centres at the Universities of Bern, Switzerland and Cape Town, South Africa. The current database includes 288,015 adults (251,759 on ART) and 30,470 children (24,277 on ART) in 23 programmes in 6 countries (Botswana, Malawi, Mozambique, South Africa and Zambia, Zimbabwe). All participating clinics collect socio-demographic, clinical, laboratory, and pharmacological data at the individual patient level, using an agreed protocol and database structure. Patients are followed up 3 to 6 monthly. VL is regularly measured in South Africa and Botswana. Outcomes include changes in virological and immunological failure of ART, mortality and loss to follow-up. We will use the IeDEA-SA data to parameterize the model, and review published transmission models and the literature to extract data on sexual behaviour (not collected in IeDEA) and partner change. We will adapt the individual-based ART model developed at ISPM Bern to include components relevant to HIV transmission (pre-ART period, individual VL and CD4 trajectories etc.), integrate the ART model into the transmission model, explore model uncertainty and validate the model, and test pre-specified hypotheses.Significance: This will be the first HIV transmission model that incorporates detailed information that reflects the realities of ART in Southern Africa. The model will predict the future course of the epidemic in the ART era under different scenarios and aid decision making. Mathematical modelling complements randomized controlled trial and epidemiological research: it is time- and cost-saving and allows testing a wealth of different strategies. The project provides an ideal environment for a PhD student and will strengthen existing collaborations with renowned mathematical modellers in the field of HIV.