CORRELATES OF ELEVATED INFLAMMATORY AND IMMUNE ACTIVATION MARKER IN THE AIDS LINKED TO INTRAVENOUS EXPERIENCE (ALIVE) COHORT: INSIGHT FOR PUBLIC HEALTH INTERVENTIONS AGAINST CHRONIC INFLAMMATION
Abstract
Background: Though extensive literature on the relationship between chronic inflammation and health outcomes has been published, the same level of attention has not been directed towards the identification of clinical and behavioral risk factors on chronic inflammation as an outcome in marginalized populations. These populations include intravenous drug users (IVDU) and individuals with HIV/Hepatitis C (HCV), whose underlying conditions may amplify the effects of chronic inflammation on the body. The pathophysiology of chronic inflammation on cardiovascular health and mortality has been well established, yet the identification of modifiable risk factors that can be targeted for public health interventions is of utmost importance to reduce disease burden associated with chronic inflammation. Data on inflammatory biomarkers TNFR1, TNFR2, and neopterin have recently become available through the AIDS Linked to IntraVenous Experience (ALIVE) study, and provide a potential surrogate measure that may be used to ascertain contributing factors for chronic inflammation.
Methods: We conducted a cross-sectional study of ALIVE participants to investigate correlates of elevated inflammatory biomarker levels. ALIVE is a prospective cohort that is comprised of current and former intravenous drug users in Baltimore, Maryland. In total, there were 1,191 participants in this analysis, and demographic information was collected through the use of questionnaires administered by trained interviewers. Self-report of drug use and risk behaviors were obtained through standardized computer-aided questionnaire. For inflammatory biomarker data collection, two duplicate measurements in subjects were taken for each biomarker to derive an average value, with average measurements subsequently log-transformed. Multivariable linear regressions were conducted comparing biomarker level to potential correlates. Additional analysis with HIV and HCV-specific covariates on biomarker concentration was carried out in HIV and HCV positive populations respectively to elucidate further trends within these at-risk groups.
Results: Of the 1,191 ALIVE participants, 322 (27%) were HIV seropositive and 1025 (86%) were HCV seropositive. The mean age was 46.8 years (SD: 7.9 years) and among the participants, 420 (35%) were female and 1043 (88%) were African American. 252 (21%) reported using intravenous drugs more than once a day, and the median number of comorbidities in the population was 1 (IQR: 1, 2). In the overall multivariate model, three key covariates were found to be strongly positively associated with TNFR1, TNFR2, and neopterin. These variables were number of non-AIDS-related comorbidities, daily intravenous drug use, and HCV/HIV status. Notably, age was only significantly associated in TNFR1 (β = 0.05, 95% CI: 0.021 - 0.079). HCV and HIV-positive patients were stratified and analyzed further to better understand covariates of interest that are of unique relevance to these populations. In the HCV subgroup, Fibroscan score showed a strong, positive association with neopterin (β = 0.541, 95% CI: 0.095 - 0.987), TNFR1 (β = 0.458, 95% CI: 0.172 - 0.743), and TNFR2 (β = 0.884, 95% CI: 0.538 - 1.229) after adjustment while HCV viral load, past hepatitis treatment, and ALT level were insignificant with inflammatory biomarker level. In the HIV subgroup, HIV viral load was statistically significant for neopterin (β = 0.236, 95% CI: 0.147 - 0.324) and TNFR2 (β = 0.123, 95% CI: 0.049 - 0.196), while HAART treatment in the past six months and CD4 nadir were not observed to possess any meaningful association with biomarker level.
Conclusions: The association between chronic inflammation and negative health outcomes has been discussed extensively throughout the scientific literature, but there is a vital need to recognize risk factors that contribute to elevated inflammation. The determination of modifiable risk factors is a public health imperative, and our results suggest several behavioral and clinical areas of focus that may be suitable for further intervention efforts. In our analysis, we identified several variables that show significant relationships with the inflammatory biomarkers of interest. In particular, our findings suggest that intravenous drug usage, non-AIDS-defining comorbidities, and HCV/HIV status show consistent statistical significance in their associations with higher levels of TNFR1, TNFR2, and neopterin. We noticed that within the HCV and HIV subgroups, additional strong positive relationships were present. Liver fibrosis was found to be closely linked with increased biomarker concentrations among HCV-positive subjects, while HIV viral load saw similarly significant associations with increased neopterin and TNFR2 levels that bring to light the additional impact of HIV-specific factors on chronic inflammation. This study served to identify potential modifiable lifestyle factors that may be targeted through public health intervention, in particular within at-risk IVDU and HIV/HCV-infected populations. Efforts to reduce injection drug use, treat underlying comorbidities such as hypertension, and increase access to antiretroviral treatments will be beneficial, and together may moderate cardiovascular disease, mortality, and other chronic inflammation-related conditions
