HIV Treatment as Prevention: Systematic Comparison of Mathematical Models of the Potential Impact of Antiretroviral Therapy on HIV Incidence in South Africa

Abstract

Background Many 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 Findings Twelve 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. 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. 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

Comparative assessment of five trials of universal HIV testing and treatment in sub‐Saharan Africa

“…Mathematical models have sought to predict the long‐term population‐level impact of UTT strategies on the epidemic 15, 16. All models have indicated that UTT could reduce HIV‐transmission, but the estimated impact of the UTT strategy on the reduction of HIV incidence ranged from 35% to 54% in the short‐term and from 32% to 74% in the longer term 16.…”

“…All models have indicated that UTT could reduce HIV‐transmission, but the estimated impact of the UTT strategy on the reduction of HIV incidence ranged from 35% to 54% in the short‐term and from 32% to 74% in the longer term 16. Furthermore, these models vary greatly in structure and in parametric assumptions and rely on context‐specific variables, such as eligibility criteria for ART initiation, uptake and coverage of HIV testing, linkage to care, treatment initiation and adherence 13.…”

Prospects of elimination of HIV with test-and-treat strategy

“…Mathematical modeling has played a key role in the discussion of the impact of treatment as prevention strategies, highlighted by the paper by Granich et al (2), and followed up by others (11)(12)(13)(14). These models all set out to assess the impact of treatment on population prevalence and incidence using simulations with parameter values estimated from various data sources.…”

Antiretroviral therapy for prevention of HIV transmission: implications for Europe

“…Modelling studies have explored the widespread use of ART but mainly in sub-Saharan settings [72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89], in the United States [90;91], in China [92][93][94], Canada [95] and for some specific groups, such as MSM in Australia [36;96;97], in Peru, Ukraine, Kenya and Thailand [98] and in different cities in the United States [99][100][101][102][103]; only a few of them model the HIV epidemic in European countries (MSM in Amsterdam, the Netherlands [104] and in the UK [105][106][107] and people who inject drugs in Russia [108]). They varied in their conclusions, although most have suggested potential appreciable beneficial effects on HIV incidence of introducing ART initiation at a higher CD4 count as a policy at a population level.…”