Predicting the Long-Term Impact of Antiretroviral Therapy Scale-Up on Population Incidence of Tuberculosis

Peter J Dodd,Stephen D Lawn,Gwenan M Knight,Elizabeth L Corbett,Richard G White,Hiroshi Nishiura

doi:10.1371/journal.pone.0075466

Abstract

ObjectiveTo investigate the impact of antiretroviral therapy (ART) on long-term population-level tuberculosis disease (TB) incidence in sub-Saharan Africa.MethodsWe used a mathematical model to consider the effect of different assumptions about life expectancy and TB risk during long-term ART under alternative scenarios for trends in population HIV incidence and ART coverage.ResultsAll the scenarios we explored predicted that the widespread introduction of ART would initially reduce population-level TB incidence. However, many modelled scenarios projected a rebound in population-level TB incidence after around 20 years. This rebound was predicted to exceed the TB incidence present before ART scale-up if decreases in HIV incidence during the same period were not sufficiently rapid or if the protective effect of ART on TB was not sustained. Nevertheless, most scenarios predicted a reduction in the cumulative TB incidence when accompanied by a relative decline in HIV incidence of more than 10% each year.ConclusionsDespite short-term benefits of ART scale-up on population TB incidence in sub-Saharan Africa, longer-term projections raise the possibility of a rebound in TB incidence. This highlights the importance of sustaining good adherence and immunologic response to ART and, crucially, the need for effective HIV preventive interventions, including early widespread implementation of ART.

Highlights

It is estimated that 79% of the global burden of HIV-associated tuberculosis disease (TB) occurs within sub-Saharan Africa [1]
Model predictions of TB incidence relative to its value before antiretroviral therapy (ART) scale up (t = 0, Figure 2A) show that with complete ART coverage and lower individual TB incidence rates, total TB incidence would initially decrease in all four depicted scenarios
In the two scenarios where HIV incidence remains constant, TB incidence tends towards a new equilibrium whose value is only dependent on the total lifetime risk of developing TB

Summary

Introduction

It is estimated that 79% of the global burden of HIV-associated tuberculosis disease (TB) occurs within sub-Saharan Africa [1] Control of this epidemic requires TB case finding and effective treatment, and preventive interventions including antiretroviral therapy (ART), isoniazid preventive therapy, intensified case finding and infection control [2]. Among these interventions, ART is the key tool, profoundly reducing all-cause mortality. ART reduces TB incidence rates in HIV cohorts over the short-term by approximately two-thirds, and this effect is observed across a broad range of baseline CD4 cell counts and independent of tuberculin skin test status [3,4,5]. Short-term benefits in TB notification rates at the population level have been observed in communities in South Africa and Malawi where ART has been scaled up rapidly [8,9]

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Conclusion