Higher Risk of Inflamm-Aging in HIV-1 Infected Patients Due to Persistent Inflammation Following Long-Term Successful Antiretroviral Therapy

Background: Long-term HIV infection, even with successful combination antiretroviral therapy (cART), is associated with an enhanced and accentuated onset of premature-aging or age-related diseases in people living with HIV (PLHIV). No data are available from low- and middle-income countries (LMICs) like India on inflamm-aging. In this study, we attempt to understand the relationship between several 'biomarkers' of inflamm-aging in a well-defined Indian cohort of PLHIV. Methods: Blood samples were obtained from therapy naive PLHIV (Pre-ART, n=43), patients on cART (ART, n=53) and age and gender-matched healthy controls (HC, n=41) after screening 714 individuals. We measured telomere length, 92 markers of inflammation, immune activation markers, and HIV-1 reservoir coupled with clinical phenotypes and neurocognitive function assessments using the International HIV Dementia Scale (IHDS). Findings: Despite a median duration of eight years of cART, sCD14 (p<0.001) and sCD163 (p=0.0377) was not normalized to the level of HC. Significant differences were observed in 11 inflammatory markers between HC and ART (p<0.05). Linear regression analysis showed a significant negative association of HIV-1 positive status on telomere length (-2.687, p<0.0001). There was a significant association between HIV status and higher odds of having IHDS ≤10 (OR:39.74, p<0.0001). A significant negative association of CCL20 (-0.5236, p=0.0219) and CCL11 (-1.1608, p=0.0338) with HIV-1 reservoir was also observed. Interpretation: Our study suggests that PLHIV on successful cART in a standardized public-health setting, may be at higher risk of inflamm-aging and age-related inflammatory diseases which may need special intervention and identifies several biomarkers for further mechanistic investigation. Funding Statement: This work was supported by grants from the Swedish Research Council Establishment Grant (2017- 01330) (U.N.) and Jeanssons Stiftelser (JS2016–0185) (U.N.). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: The study was approved by the Institutional Ethics Committee of the National Institute for Research in Tuberculosis (NIRT IEC No: 2015023 and TRC IEC No: 2011001) and Institutional Review Board Committee of Government Hospital for Thoracic Medicine (GHTM-27102015). All the study participants gave written informed consent. Patient identities were anonymized and delinked before analysis.