Death during MDR-TB treatment more likely in people with HIV and underweight or most drug-resistant patients

People living with HIV, those who are underweight and those with more extensive drug resistance are more likely to die during treatment for multi-drug resistant tuberculosis (MDR-TB), a nine-country study has found. The findings were presented at the 46th Union World Conference on Lung Health in Cape Town last week.

People diagnosed with multi-drug 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 46^th Union World Conference looked at the two-year mortality of people starting second-line TB treatment between January 2005 and December 2008 in nine countries in Africa, Asia, Eastern Europe and Latin America.

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

The study evaluated participants according to five pre-defined World Health Organization (WHO) criteria: cure, completed treatment, lost to follow-up, treatment failure or death.

The study enrolled 1659 participants, of which 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 comprised 1550 patients. 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 two years.

Study participants had a median age of 37, 36% were women and HIV prevalence was 18.5% – but in South Africa just over half of participants was living with HIV.

Fifty-seven per cent of study participants were enrolled in two countries – South Africa and the Philippines – but 62% of all deaths in the study occurred in South Africa alone.

Overall, 191 people died during the first two years after beginning treatment (14%). 13.9% of patients who previously received first-line medications for TB died during MDR-TB treatment; 11.5% of those who had received second-line medications died. The death rate was especially high among people with HIV (27.7%) and those who were underweight at baseline (BMI < 18.5) (19.6%).

Those with resistance to at least one fluoroquinolone and to at least one injectable second-line drug (classified as extensively drug resistant, or XDR-TB) died more frequently than those with resistance to a fluoroquinolone alone (28.6% vs 22.1%), but multivariable analysis found that resistance to either a fluoroquinolone or to an injectable was independently predictive of an increased risk of death during MDR-TB treatment (adjusted hazard ratio 2.2, p < 0.001).

People who were underweight (aHR 2.7, p < 0.001) or HIV-positive (aHR 1.8, p = 0.01) were also at increased risk of dying during the first two 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 treatment at baseline, so it is unclear how this might affect outcomes.

Presenting the findings, Hannah Kirking of the US Centers for Disease Control Division of HIV/AIDS and TB 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 optimise MDR-TB treatment.