Background:
Tuberculosis (TB) is the leading cause of death in people living with HIV. While antitubercular treatment (ATT) is generally effective, monitoring the biological response to therapy in HIV-coinfected individuals remains a significant challenge due to advanced immunosuppression and systemic inflammation. There is an urgent need for blood-based biomarkers that can accurately track treatment response and predict clinical outcomes in this high-risk population to guide more personalized management strategies.
Abstract:
Methods: This prospective cohort study followed hospitalized HIV-positive adults with new tuberculosis diagnoses in Cape Town, South Africa. We measured a broad panel of 28 host soluble inflammatory mediators in plasma at baseline and evaluated their association with treatment response and 12-week mortality.
Results: A distinct immune profile, characterized by elevated mediators of the innate immune response and chemotaxis (such as IL-6, IL-8, IP-10, and IL-1Ra), was strongly associated with a lack of treatment response and early death. Conversely, higher levels of T-cell-associated mediators (IL-2, IFN-$\gamma$, IL-12p70) and growth factors were associated with survival and better clinical stabilization. This innate inflammatory signature also correlated significantly with markers of disseminated TB, such as mycobacteremia and urine LAM positivity.
Conclusion: Systemic innate immune activation is a critical determinant of poor treatment response and mortality in HIV-associated TB. These inflammatory biomarkers provide a rationale for investigating host-directed therapies and could serve as tools for risk stratification in acutely ill patients.
Keywords: HIV-associated tuberculosis; treatment response; inflammatory mediators; biomarkers; innate immunity.
Clique aqui
- Data de Publicação: 09/12/2019
- Autores: Catarina D. Fernandes1,2,3*, María B. Arriaga1,2,5*, Maria Carolina M. Costa1,2,4, Maria Clara M. Costa1,2,4, Maria Heloina M. Costa5 , Caian L. Vinhaes1,2,4, Paulo S. Silveira- Mattos1,2,4,5, Kiyoshi F. Fukutani1,2,4*, Bruno B. Andrade1,2,3,4,6,7,8*
