CD14+CD16-Low Monocyte Subset Predicts Non-Progressive HIV Disease: Evidence of A New Prognostic and Diagnostic Biomarker

Abstract

Monocytes are phenotypically pliable, which allows them to play several significant immunological roles in combating HIV infection. Monocytes can be subcategorized into subsets based on the expression of CD14 and CD16 antigens. Although the CD4+ T cell counts have been shown to predict HIV viremia, the actual predictive value of these monocyte subsets at different stages of plasma viremia is not known. We derived ex-vivo monocytes from HIV+ patients with detectable and below detectable plasma viremia, HIV+ Long-Term Non-Progressors (LTNP) and HIV negative individuals. We subdivided monocytes into CD14+/ CD16-low, medium and high populations and visualized the phenotypic changes in expression of both CD14 and CD16 antigens in HIV+ patients at different stages of HIV disease.The expression of surface markers on monocytes (CD14+/CD16) was measured from the EDTA blood of 50 HIV+ individuals [14 viremic and 29 Below Detectable Level (BDL) whilst on HAART, 7 therapy naïve, aviremic LTNP's] and 6 HIVnegative donors using the FACSCanto (6-color) flow cytometer. Percentage of CD16/CD14+ sub-populations were measured on FACSCantoA with FACSDiva (v 6.1.2) software and analysed by FlowJo software (v10.0.7), respectively.By categorizing monocyte population into CD14+, CD16 high, medium and low, we could clearly discriminate between viremic and aviremic HIV patients. There was considerable elevation of CD16-low population (80%) in HIV-negative individuals and LTNPS (57%), as opposed to 9% in HAART-treated group. Noteworthy was the CD16-low population failed to recover despite complete viral control during HAART therapy suggesting their definitive role as indicators of viremic control as seen with their marked prominence in LTNPs. In contrast, the HAART-treated group showed elevated CD16-high populations (34%), as opposed to relatively low percentages in the viremic group (3%). The robust maintenance and elevation of CD16-low populations and substantial low levels of CD16-high populations distinctively in HIV-negative and non-progressing HIV+ individuals correlated with the natural control of HIV in LTNPs. This feature of CD16-low monocytic population can be exploited as a biomarker in predicting plasma viremia and the strength of the immune system.