WCLH 2015: Death During MDR-TB Treatment More Likely in HIV+ and Underweight Patients


People living with HIV, those who are underweight, and those with more extensive drug resistance are more likely to die during treatment for multidrug-resistant tuberculosis (MDR-TB) in a 9-country study, according to a presentation at the 46th Union World Conference on Lung Health in Cape Town this month.

[Produced in collaboration with]

People diagnosed with multidrug-resistant TB are known to have poor outcomes compared to people diagnosed with drug-sensitive TB, but there are few data to provide a reliable assessment of the death rate in MDR-TB patients, nor do clinicians have a detailed picture of which patients are at greater risk of death and therefore in need of especially close monitoring during MDR-TB treatment.

The Global Preserving Effective TB Treatment Study (PETTS) was an international observational cohort study designed to establish risk factors for acquisition of TB drug resistance and the impact of acquired resistance on treatment outcomes. Primary results of the study were published in 2012.

The analysis of the PETTS cohort presented at the Union World Conference looked at the 2-year mortality of people starting second-line TB treatment between January 2005 and December 2008 in 9 countries in Africa, Asia, Eastern Europe, and Latin America; 57% of study participants were enrolled in 2 countries -- South Africa and the Philippines -- but 62% of all deaths in the study occurred in South Africa alone.

The analysis included all adults recruited to the cohort study who had received at least 1 month of treatment, and excluded pregnant women, prisoners, and children aged under age 18, as well as anyone with extrapulmonary TB.

The study enrolled 1659 participants, of whom 52 were excluded from the final analysis due to missing outcomes data and 55 were excluded due to lack of information on the time to outcome; the final analysis included 1550 patients. About a third of study participants (36%) were women, the median age was 37, and HIV prevalence was 19% -- although in South Africa just over half of participants were living with HIV.

The study evaluated participants according to 5 pre-defined World Health Organization criteria: cure, completed treatment, loss to follow-up, treatment failure, or death. The analysis censored the follow-up period after achieving any outcome apart from death, and also censored participants who had achieved no final outcome of treatment after 2 years.

Overall, 191 people (14%) died during the first 2 years after beginning treatment; 14% of patients who previously received first-line medications for TB died during MDR-TB treatment, as did 12% of those who had received second-line medications. The death rate was especially high among people with HIV (28%) and those who were underweight at baseline (BMI <18.5) (20%).

Participants with resistance to at least 1 fluoroquinolone and at least 1 injectable second-line drug (classified as extensively drug resistant, or XDR-TB) died more frequently than those with resistance to a fluoroquinolone alone (27% vs 22%), but multivariable analysis found that resistance to either a fluoroquinolone or to an injectable agent was independently predictive of an increased risk of death during MDR-TB treatment (adjusted hazard ratio [HR] 2.2).

People who were underweight (adjusted HR 2.7) or HIV-positive (adjusted HR 1.8) were also at increased risk of dying during the first 2 years after beginning treatment.

Country differences in outcomes or risk factors were not presented. In particular, the study did not report whether participants with HIV were receiving antiretroviral therapy at baseline, so it is unclear how this might affect outcomes.

Presenting the findings, Hannah Kirking of the U.S. Centers for Disease Control and Prevention said that clinicians should be aware of the factors amenable to interventions that affect outcomes of MDR-TB treatment. Antiretroviral treatment and interventions to increase body weight could have an impact on outcomes, as could greater use of drug susceptibility testing to optimize MDR-TB treatment.



H Kirking, M Yagui Moscoso, M Van Der Walt, et al (the Global PETTS Investigators). Mortality among patients treated for multidrug-resistant tuberculosis in nine countries, 2005-2010. 46th Union World Conference on Lung Health. Cape Town, December 2-6, 2015.Abstract OA-347-04.