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Exposure to pulmonary tuberculosis (PTB) culminates in heterogeneous outcomes, including variation in Mtb antigen-specific interferon-gamma (IFN-γ) T-cell responses. IFN-γ-independent cytokines, including tumor necrosis factor (TNF) and interleukin (IL-2), offer potential diagnostic improvements and insights into pathogenesis. We hypothesized that ESAT6/CFP10 TNF and IL-2 responses improve Mtb infection detection among exposed household contacts (HHCs) and are associated with index case Mtb aerosolization (i.e., cough aerosol culture positive for Mtb growth, CAC+) and HIV co-infection. We enrolled individuals with PTB and their HHCs in a longitudinal study in Nairobi, Kenya. We measured TNF and IL-2 in HHCs from QuantiFERON-TB Plus TB1 tube supernatants. An additional 9.2% (25) HHCs beyond the 58.6% (129) with an IFN-γ response demonstrated an antigen-specific increase in IL-2 and TNF. HHCs of CAC + participants were more likely to have positive IL-2 (84.6% vs. 53.8%, p = 0.02) and IFN-γ (88.0% vs. 54.9%, p = 0.01), but not TNF responses, compared to CAC-negative individuals. While HIV co-infection in the index was negatively associated with IFN-γ responses in HHCs (35.7% vs. 62.3%, p = 0.03), IL-2 and TNF responses did not differ. Antigen-specific ESAT6/CFP10 IL-2 and TNF may increase rates of Mtb infection detection and provide insights into Mtb transmission and pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Understanding trends in patient profiles and identifying predictors for adverse outcomes are key to improving the effectiveness of HIV care and treatment programs. Previous work in Kenya has documented findings from a rural setting. This paper describes trends in demographic and clinical characteristics of antiretroviral therapy (ART) treatment cohorts at a large urban, referral HIV clinic and explores treatment outcomes and factors associated with attrition during 12 years of follow-up. Methods: This was a retrospective cohort analysis of HIV-infected adults who started ART between January 1, 2004, and September 30, 2015. ART-experienced patients and those with missing data were excluded. The Cochran–Armitage test was used to determine trends in baseline characteristics over time. Cox proportional hazards models were used to determine the effect of baseline characteristics on attrition. Results: ART uptake among older adolescents (15–19 years), youth, and young adults increased over time (p=0.0001). Independent predictors for attrition included (adjusted hazard ratio [95% CI]) male sex: 1.30 (1.16–1.45), p=0.0001; age: 15–19 years: 1.83 (1.26–2.66), p=0.0014; 20–24 years: 1.93 (1.52–2.44), p=0.0001; and 25–29 years: 1.31 (1.11–1.54), p=0.0012; marital status – single: 1.27 (1.11–1.44), p=0.0005; and divorced/separated: 1.56 (1.30–1.87), p=0.0001; urban residence: 1.40 (1.20–1.64), p=0.0001; entry into HIV care following hospitalization: 1.31 (1.10–1.57), p=0.0026, or transfer from another facility: 1.60 (1.26–2.04), p=0.0001; initiation of ART more than 12 months after the date of HIV diagnosis: 1.36 (1.19–1.55), p=0.0001, and history of a current or past opportunistic infection (OI): 1.15 (1.02–1.30), p=0.0284. Conclusion: Although ART uptake among adolescents and young people increased over time, this group was at increased risk for attrition. Single marital status, urban residence, history of hospitalization or OI, and delayed initiation of ART also predicted attrition. This calls for focused evidence-informed strategies to address attrition and improve outcomes. [ABSTRACT FROM AUTHOR]

Exposure to pulmonary tuberculosis (PTB) culminates in heterogeneous outcomes, including variation in Mtb antigen-specific interferon-gamma (IFN-γ) T-cell responses. IFN-γ-independent cytokines, including tumor necrosis factor (TNF) and interleukin (IL-2), offer potential diagnostic improvements and insights into pathogenesis. We hypothesized that ESAT6/CFP10 TNF and IL-2 responses improve Mtb infection detection among exposed household contacts (HHCs) and are associated with index case Mtb aerosolization (i.e., cough aerosol culture positive for Mtb growth, CAC+]) and HIV co-infection. We enrolled individuals with PTB and their HHCs in a longitudinal study in Nairobi, Kenya. We measured TNF and IL-2 in HHCs from QuantiFERON-TB Plus TB1 tube supernatants. An additional 9.2% (25) HHCs beyond the 58.6% (129) with an IFN-γ response demonstrated an antigen-specific increase in IL-2 and TNF. HHCs of CAC + participants were more likely to have positive IL-2 (84.6% vs. 53.8%, p = 0.02) and IFN-γ (88.0% vs. 54.9%, p = 0.01), but not TNF responses, compared to CAC-negative individuals. While HIV co-infection in the index was negatively associated with IFN-γ responses in HHCs (35.7% vs. 62.3%, p = 0.03), IL-2 and TNF responses did not differ. Antigen-specific ESAT6/CFP10 IL-2 and TNF may increase rates of Mtb infection detection and provide insights into Mtb transmission and pathogenesis., Competing Interests: Declaration of Competing Interests: The authors declare that they have no commercial or financial conflicts of interest relevant to this article to disclose.

Background: Understanding trends in patient profiles and identifying predictors for adverse outcomes are key to improving the effectiveness of HIV care and treatment programs. Previous work in Kenya has documented findings from a rural setting. This paper describes trends in demographic and clinical characteristics of antiretroviral therapy (ART) treatment cohorts at a large urban, referral HIV clinic and explores treatment outcomes and factors associated with attrition during 12 years of follow-up., Methods: This was a retrospective cohort analysis of HIV-infected adults who started ART between January 1, 2004, and September 30, 2015. ART-experienced patients and those with missing data were excluded. The Cochran-Armitage test was used to determine trends in baseline characteristics over time. Cox proportional hazards models were used to determine the effect of baseline characteristics on attrition., Results: ART uptake among older adolescents (15-19 years), youth, and young adults increased over time ( p =0.0001). Independent predictors for attrition included (adjusted hazard ratio [95% CI]) male sex: 1.30 (1.16-1.45), p =0.0001; age: 15-19 years: 1.83 (1.26-2.66), p =0.0014; 20-24 years: 1.93 (1.52-2.44), p =0.0001; and 25-29 years: 1.31 (1.11-1.54), p =0.0012; marital status - single: 1.27 (1.11-1.44), p =0.0005; and divorced/separated: 1.56 (1.30-1.87), p =0.0001; urban residence: 1.40 (1.20-1.64), p =0.0001; entry into HIV care following hospitalization: 1.31 (1.10-1.57), p =0.0026, or transfer from another facility: 1.60 (1.26-2.04), p =0.0001; initiation of ART more than 12 months after the date of HIV diagnosis: 1.36 (1.19-1.55), p =0.0001, and history of a current or past opportunistic infection (OI): 1.15 (1.02-1.30), p =0.0284., Conclusion: Although ART uptake among adolescents and young people increased over time, this group was at increased risk for attrition. Single marital status, urban residence, history of hospitalization or OI, and delayed initiation of ART also predicted attrition. This calls for focused evidence-informed strategies to address attrition and improve outcomes., Competing Interests: Disclosure The authors report no conflicts of interest in this work.