Low body mass index as a predictor of sputum culture conversion and treatment outcomes among patients receiving treatment for multidrug-resistant tuberculosis in Lesotho.

BACKGROUND: A low body mass index (BMI) at the start of treatment for rifampicin- or multidrug-resistant tuberculosis (MDR/RR-TB) is associated with poor treatment outcomes and may contribute to delayed sputum culture conversion, thereby prolonging the period of potential transmission to others. Whether the relative importance of low BMI in predicting treatment outcomes differs by HIV status is unclear. OBJECTIVES: We evaluated the association between low BMI and two dependent variables, sputum culture conversion and end-of-treatment outcome, among patients receiving treatment for MDR/RR-TB in Lesotho, a setting with a high prevalence of HIV infection. METHODS: Secondary data from a prospective cohort of patients initiating a longer (18-20 months) treatment containing bedaquiline and/or delamanid under routine programmatic conditions in Lesotho were analysed. Risk ratios and differences were adjusted for potential confounders using multivariable logistic regression, and estimates were stratified by HIV status. RESULTS: Of 264 patients, 105 and 250 were eligible for culture conversion and end-of-treatment analyses, respectively. Seventy-one per cent of patients (74/105) experienced culture conversion within six months, while 74% (184/250) experienced a favourable end-of-treatment outcome. Low BMI was associated with a lower frequency of culture conversion at six months among those who were not living with HIV (relative risk [RR]: 0.50 [95% CI: 0.21, 0.79]); this association was attenuated among those living with HIV (RR: 0.88 [95% CI: 0.68, 1.23]). A low BMI was moderately associated with a lower frequency of treatment success (RR = 0.89 [95% CI: 0.77, 1.03]), regardless of HIV status. CONCLUSIONS: Low BMI was common and associated with the frequency of six-month culture conversion and end-of-treatment outcomes. The association with culture conversion was more pronounced among those not living with HIV. Addressing the myriad factors that drive low BMI in this setting could hasten culture conversion and improve end-of-treatment outcomes. This will require a multipronged approach focused on alleviating food insecurity and enabling prompt diagnosis and treatment of HIV and TB.

Comparative effectiveness of adding delamanid to a multidrug-resistant tuberculosis regimen comprised of three drugs likely to be effective.

Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen hastened culture conversion; the results of the Phase III trial were equivocal. We evaluated the effect of adding delamanid for 24 weeks to three-drug MDR/RR-TB regimens on two- and six-month culture conversion in the endTB observational study. We used pooled logistic regression to estimate the observational analogue of the intention-to-treat effect (aITT) adjusting for baseline confounders and to estimate the observational analogue of the per-protocol effect (aPP) using inverse probability of censoring weighting to control for time-varying confounding. At treatment initiation, 362 patients received three likely effective drugs (delamanid-free) or three likely effective drugs plus delamanid (delamanid-containing). Over 80% of patients received two to three Group A drugs (bedaquiline, linezolid, moxifloxacin/levofloxacin) in their regimen. We found no evidence the addition of delamanid to a three-drug regimen increased two-month (aITT relative risk: 0.90 (95% CI: 0.73-1.11), aPP relative risk: 0.89 (95% CI: 0.66-1.21)) or six-month culture conversion (aITT relative risk: 0.94 (95% CI: 0.84, 1.02), aPP relative risk: 0.93 (95% CI: 0.83, 1.04)). In regimens containing combinations of three likely effective, highly active anti-TB drugs the addition of delamanid had no discernible effect on culture conversion at two or six months. As the standard of care for MDR/RR-TB treatment becomes more potent, it may become increasingly difficult to detect the benefit of adding a single agent to standard of care MDR/RR-TB regimens. Novel approaches like those implemented may help account for background regimens and establish effectiveness of new chemical entities.