Antiretroviral Treatment Scale-Up and Tuberculosis Mortality in High TB/HIV Burden Countries: An Econometric Analysis

Abstract

Introduction: Antiretroviral therapy (ART) reduces mortality in patients with active tuberculosis (TB), but the population-level relationship between ART coverage and TB mortality is untested. We estimated the reduction in population-level TB mortality that can be attributed to increasing ART coverage across 41 high HIV-TB burden countries.

Methods: We compiled TB mortality trends between 1996 and 2011 from two sources: (1) national program-reported TB death notifications, adjusted for annual TB case detection rates, and (2) WHO TB mortality estimates. National coverage with ART, as proportion of HIV-infected people in need, was obtained from UNAIDS. We applied panel linear regressions controlling for HIV prevalence (5-year lagged), coverage of TB interventions (estimated by WHO and UNAIDS), gross domestic product per capita, health spending from domestic sources, urbanization, and country fixed effects.

Results: Models suggest that that increasing ART coverage was followed by reduced TB mortality, across multiple specifications. For death notifications at 2 to 5 years following a given ART scale-up, a 1% increase in ART coverage predicted 0.95% faster mortality rate decline (p = 0.002); resulting in 27% fewer TB deaths in 2011 alone than would have occurred without ART. Based on WHO death estimates, a 1% increase in ART predicted a 1.0% reduced TB death rate (p<0.001), and 31% fewer deaths in 2011. TB mortality was higher at higher HIV prevalence (p<0.001), but not related to coverage of isoniazid preventive therapy, cotrimoxazole preventive therapy, or other covariates.

Conclusion: This econometric analysis supports a substantial impact of ART on population-level TB mortality realized already within the first decade of ART scale-up, that is apparent despite variable-quality mortality data.

Fig 1. (a) HIV and (b) TB mortality and intervention coverage, and (c) TB mortality relative to start of ART scale-up.

Totals across 41 high TB/HIV burden countries. In Fig 1c, the mortality rate of each country (which are all weighted equally) is included as the difference between the country’s year-specific mortality (per 100,000 person-years) and its mean mortality over 1996 to 2011 (de-meaned). Blue line with ‘x’ marker: WHO estimate of TB deaths; Green line with triangle marker: Notification-based TB deaths with authors’ adjustment for notification completeness, including eight death notification categories (see Methods); Red line with ‘+’ marker: Notification-based TB deaths with authors’ adjustment for notification completeness, limited to smear-positive patients.

Fig 2. WHO-estimated (left), notification-based (right) and model-predicted TB mortality following ART scale-up, in Namibia; Rwanda; Thailand; and Togo.

Dashed lines give 95% confidence interval. Model predictions use a 2-year time lag.

Fig 3. WHO-estimated, notification-based and model-predicted TB mortality, following ART scale-up, in (a & b) 19 high TB/HIV countries with below median ART coverage; (c & d) 18 high TB/HIV countries with above median ART coverage.

Dashed lines give 95% confidence interval. Model predictions use a 2-year time lag. Split into below median versus above median ART coverage was based on ART coverage averaged over 1996–2012.