In patients with HIV and TB coinfection, initiation of antiretroviral (ART) and anti-tubercular therapy (ATT) results in marked improvement in the 6-minute walk distance (6MWD) as well as lung function, according to a recent study published in BMC Pulmonary Medicine.¹

A secondary analysis of the prospective Lung Function after TB-IRIS (LIFT-IRIS) study conducted in South Africa was performed to determine factors associated with change in the 6MWT in the initial 24 weeks of ART and ATT. The gap between the initiation of the two treatments was 30 days (mean). The LIFT-IRIS study had included adults with newly-diagnosed HIV and TB who had started their ATT within a month of being diagnosed with TB and were ART-naïve. Eighty-nine patients were included for the secondary analysis. Their mean age was 37.2 years and 58% of them were male. The distance walked on the 6-minute walk test (6MWT) and lung function using spirometry were evaluated at 0 (baseline), 4, 12, and 24 weeks; the levels of biomarkers were also measured at 0 (baseline), 4, 12 weeks. These biomarkers included C-X-C motif chemokine 10 (CXCL-10), CXCL-11, matrix metalloproteinases-1 (MMP-1), plasminogen activator, macrophage colony-stimulating factor (M-CSF), chemokine (C-C) motif-2 (CCL-2), tissue inhibitor of MMP (TIMP)-1, collagen 1a, IL-6, IL-8, vascular cell adhesion molecule 1 (VCAM-1) and vascular endothelial growth factor.

The 6MWD increased from 393 m at baseline to 430 (69.6) meters at week 24 showing an improvement of 9% after the patients were started on ART. The threshold for the minimum clinically important difference (MCID) in the change in the 6 min walk test distance during treatment was 41 m. Nearly half (48%) of the patients achieved this cut-off or greater. These were the patients who had poor lung function, lower 6MWD and higher levels of proinflammatory biomarkers including TIMP-1 and M-CSF and low collagen 1a levels at the time of their recruitment in the study.

Patients who had an MCID at week 24 were significantly more likely to have increased forced expiratory volume in 1 second percent predicted (odds ratio 1.20) and forced vital capacity percent predicted (OR 1.22) between baseline and week 12. They also had greater odds of high levels of collagen 1a levels (OR 1.31). “Increased collagen 1a levels at weeks 4 and 12 (OR 1.31) and increased levels of CXCL-10 at week 4 (OR 1.08) were significantly associated with increased adjusted odds of an MCID in 6-minute walk test distance.”

This study shows that initiation of ATT and ART in patients with TB and HIV results in significant improvement in the 6MWD gradually. Patients who reached the cut-off of MCID as defined in the present study had more severe disease at baseline. These were also the patients in whom the lung function and collagen 1a levels increased during treatment. These findings illustrate the beneficial effects of treatment on the “physical capacity of patients beyond lung function” in this group of patients. The authors further state that the 6-minute walk test “may serve as a complementary measure to follow up post-TB sequelae.”

Reference

1. Baik Y, et al. Lung function and collagen 1a levels are associated with changes in 6 min walk test distance during treatment of TB among HIV-infected adults: a prospective cohort study. BMC Pulm Med. 2023 Feb 3;23(1):53. doi: 10.1186/s12890-023-02325-7.