Matrix metallopeptidase plasma levels among HIV-infected children and adolescents with and without HIV-associated chronic lung disease

Abstract

Background and objectives: Among HIV-infected children and adolescents who are receiving antiretroviral therapy, chronic lung disease (CLD) is a major cause of morbidity and mortality. Matrix metallopeptidases (MMPs) are involved in a wide range of physiological processes including the breakdown and turn-over of extracellular matrix. The majority of clinical studies investigating the role of MMPs in lung pathology have been conducted among adults and none have been focused on children with HIV infection and CLD. The objectives of this study were to measure and compare the plasma levels of MMPs among HIV-infected children with and without CLD and investigate the associations between plasma MMPs levels and clinical and laboratory parameters among study participants. Methods: Data was collected as part of the BREATHE trial, a double-blind, randomized controlled trial in Harare (Zimbabwe) and Blantyre (Malawi). In total 296 children and adolescents were included in the study. Anamnestic data, spirometry and blood samples were obtained from study participants. Statistical differences between groups were calculated using the Mann-Whitney U test and chi-square test. Associations between MMPs and other study parameters were analyzed using regression and were adjusted for age, sex, being underweight, ART regimen and prior treatment for TB. Results: MMP-1, -7, -8, -10 and -12 were significantly higher among participants with CLD compared to participants without CLD. MMP-10 was significantly higher among those treated for TB (3.09 [IQR 2.88-3.24] vs. 2.94 [IQR 2.81-3.11], P=0.006). Logistical regression showed a significant association between presence of CLD and elevated plasma levels of MMP-1 (OR=3.169 (95% CI 1.257 – 7.988), P=0.014), MMP-7 (OR= 4.981 (95% CI 1.626 – 15.262), P=0.005) and MMP-10 (8.487 (95% CI 2.102 – 34.265), P=0.003). Conclusions: In this population of HIV-infected sub-Saharan African children and adolescents, a significant association between CLD status and elevated plasma levels of MMP-1, -7 and -10 was found. These results suggest that those with CLD may have upregulated expression or dysfunctional regulation of MMPs which may lead to sustained lung impairment.