Lung Function Associated With 6-Minute Walk Test in Patients With TB and HIV

Antiretroviral therapy (ART) and tuberculosis (TB) treatment are associated with substantial improvement in 6-minute walk test distance (6MWD) at 24 weeks and improved lung function in patients with TB and HIV infection, according to study findings published in BMC Pulmonary Medicine.

Researchers used 6MWD to assess the association between physical function and the effectiveness of ART and anti-tubercular therapy in patients with HIV/TB co-infection. The findings are from a secondary analysis of The Lung Function after TB-IRIS (LIFT-IRIS) study, which was conducted in Gauteng, South Africa, from July 2016 to March 2018.

Researchers for LIFT-IRIS enrolled adults with HIV and TB who initiated anti-TB treatment within 30 days of TB diagnosis and were ART-naïve.

The 6-minute walk test distance, lung function, and symptom scores on the chronic obstructive pulmonary disease (COPD) assessment test were analyzed at baseline and at weeks 4, 12, and 24. Biomarkers were assessed at baseline, week 4, and week 12, during the peak of TB-associated inflammation.

The biomarkers assessed included matrix metalloproteinases-1 (MMP-1), tissue inhibitor of MMP (TIMP)-1, collagen 1a, interleukin-6 (IL-6), interleukin-8 (IL-8), vascular cell adhesion molecule 1 (VCAM-1), C-X-C motif chemokine 10 (CXCL-10), CXCL-11, macrophage colony-stimulating factor (M-CSF), plasminogen activator, vascular endothelial growth factor, and chemokine (C-C) motif-2 (CCL-2).

The main analyses used logistic regression to examine how the odds of a minimum clinically important difference (MCID) in 6MWD at week 24 related to baseline characteristics, including lung function and biomarker levels, as well as the associations between changes in clinical characteristics from baseline to weeks 4 and 12.

Of 128 patients with a baseline 6MWD, 89 (70%) completed the test at week 24 and were included. The participants had a mean (SD) age of 37.2 (8.1) years, and 58% were male. The mean time between TB treatment initiation and ART initiation was 30 (18) days.

After initiation of ART, the mean 6MWD increased from 393 (68.5) meters at baseline to 430 (69.6) meters at week 24, which was about a 9% improvement.

The cutoff for MCID in the 6MWD during 24 weeks of treatment was 41 m, and 43 (48%) patients had an increased distance equal to this amount or greater. Higher pre-ART levels of TIMP-1 and MCSF and lower levels of collagen 1a also were associated with an increased odds of having an MCID in 6MWD at week 24.

An increased odds of an MCID in 6MWD by week 24 was significantly associated with greater increases in forced expiratory volume in 1 second percent predicted (odds ratio [OR], 1.20; 95% CI, 1.03-1.43; P =.04) and forced vital capacity percent predicted (OR, 1.22; 95% CI, 1.01-1.52; P =.05) between baseline and week 12.

Increased collagen 1a levels at weeks 4 and 12 (OR, 1.31; 95% CI, 1.08-1.62; P =.02) and increased levels of CXCL-10 at week 4 (OR, 1.08; 95% CI, 1.00-1.22; P =.05) were significantly associated with increased adjusted odds of an MCID in 6-minute walk test distance.

Study limitations include a high rate of loss to follow-up (30%) at week 24, and the researchers did not track CD4 counts or body mass index changes during ART, which may have been associated with the 6MWD at week 24. Also, plasma marker levels after week 12 were not available, and bias in the 6-minute walk test may have been introduced owing to patient misunderstanding of the test instructions.

“Taken together, these findings highlight the beneficial effects of treating HIV and TB on physical function and suggest distinct dynamics of inflammatory and certain tissue repair processes,” stated the study authors. “Furthermore, the 6-minute walk test provides some insight into the physical capacity of patients beyond lung function, and therefore may serve as a complementary measure to follow up post-TB sequelae.”