Abstract
BackgroundMany mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART.Methods and FindingsTwelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results.ConclusionsMathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact. Please see later in the article for the Editors' Summary
Highlights
There has recently been increasing interest in expanding provision of antiretroviral therapy (ART) as a tool for reducing the spread of HIV in generalised epidemics in sub-Saharan Africa [1,2,3,4,5]
The impact of an intervention was measured by comparing the number of new infections in the intervention scenario with that in a counterfactual epidemic simulation in which no ART is provided within the same model population
All of the models predicted that ART should already have had a substantial impact on the HIV epidemic, estimating that HIV incidence in year 2011 was between 17% and 32% lower than it would have been in the absence of ART
Summary
There has recently been increasing interest in expanding provision of antiretroviral therapy (ART) as a tool for reducing the spread of HIV in generalised epidemics in sub-Saharan Africa [1,2,3,4,5]. More recent modelling has shown more optimism about the potential for treatment to reduce new HIV infections in this region, with much work focused on the setting of South Africa, home to one in six people living with HIV globally [33]. Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Conclusions: Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. This target has still not been reached, by the end of 2010, 6.6 million of the estimated 15 million people in need of ART in developing countries were receiving ART
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