(P22) Correlation of inflammatory biomarkers with the HIV reservoir under long-term suppressive ART in India

Författare/Medförfattare

Sara Svensson Akusjärvi [1], Hemalatha Babu[1,2], Anoop T Ambikan[1], Erin E Gabriel[3], Luke E Hanna[2], Anders Sönnerborg[1,4], Ujjwal Neogi[1]

Affiliates

Division of Clinical Microbiology, Ana Futura Laboratory, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden[1], Department of HIV/AIDS, National Institute for Research in Tuberculosis, ICMR, Chennai, India[2], Department of Medical Epidemiology and Biostatistics and Institute of Environmental Medicine both of Karolinska Institutet Stockholm, Sweden[3], Department of Medicine Huddinge, Division of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden[4]

Abstract

Background
Antiretroviral therapy (ART) has proven sufficient at substantially reducing the body of active HIV-1 infection but the distress it and the remaining potential low-grade replication puts on the immune system is still unknown. Individuals who are suppressed with undetectable viral levels (<50copies/mL) have an life expectancy approaching uninfected individuals but studies have reported earlier development of age related diseases such as cancer, myocardial infarction and diabetes. To further elucidate the effect HIV-1 has on immunological ageing and earlier onset of age related diseases the correlation of clinical parameters together with the immune function can be studied. Here we have done a comparison between total HIV-1 DNA in PBMCs as a surrogate marker of HIV-1 reservoir and plasma inflammatory markers after adjusting for baseline clinical parameters.

Methods
The patients had been given first-line treatment (two NRTIs and one NNRTI) for more than five years (ART, n=48), collected from Chennai, India. No switch in therapy and stable CD4 counts for the past year while being on ART were required together with no known co-infections or co-morbidities and viral load <150 copies/mL. Total HIV DNA was quantified using Internally Controlled qPCR (IC-qPCR). Plasma was evaluated using the Olink Inflammation panel including 92 soluble biomarkers by proximity extension assay (PEA). sCD14 was measured by ELISA by Human CD14 Quantikine ELISA (Kit R&D Systems) The amount of HIV DNA was correlated to inflammatory biomarkers using linear regression in R after adjusting for clinical parameters (age, length of treatment, baseline CD4 count, CD4:CD8 ratio, treatment regimen).

Results
The median of total HIV DNA count in the ART group was 2.870 (2.631-3.156) log10copies/mL. A significant negative association was observed between the duration of treatment and the proviral load by univariate linear regression (-0.1898, 95%CI: -4.019, -1.715, p=0.0128). However, no association was observed between these two parameters after adjusting for baseline CD4, CD4 and CD4:CD8 ratio at sampling and treatment regimen (-0.155, 95%CI: -0.340, 0.030 p=0.0968). Linear regression analysis between the proviral load and inflammatory biomarkers showed a significant negative association between the proviral load and the C-C motif chemokine 20 (CCL20) (-0.5236, 95% CI:-0.966, -0.081, p=0.0219) and Eotaxin (CCL11) (-1.1608, 95%CI:-2.227, -0.095, p=0.0338) after adjusting for age, gender, duration of treatment, baseline CD4, CD4:CD8 ratio and sCD14.

Conclusions
Herein we showed that the total proviral load in PBMCs is not affected by length of treatment in an Indian HIV-1 cohort after adjusting for baseline CD4 and CD4:CD8 ratio. However, from a panel of inflammatory biomarkers we found that both CCL20 and CCL11 are negatively associated with the proviral load in ART treated individuals. Both CCL20 and CCL11 have earlier been proposed to play a role in seeding and persistence of the HIV reservoir and it is of interest to understand the role they play during suppressive ART.