Background
We previously reported that low-level viremia (LLV) (50-200 copies/mL) increases cellular activation and senescence in people with HIV (PWH), phenomena closely related to the development of cancer and cardiovascular diseases (CVD). However, data on the clinical consequences of LLV remain limited, especially in the integrase strand transfer inhibitors (INSTI) era. Our aim was to explore how LLV impacts on soluble and cellular markers related to these pathologies
Methods
Cross-sectional observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with suppressed viremia (SV) and 27 non-HIV controls (NHC). 28 immune checkpoints (ICs) and 18 cardiometabolic markers were evaluated in plasma by immunoassays. Tregs cells were characterized by spectral flow cytometry. Differences between groups were adjusted by age, sex at birth and antiretroviral therapy (ART). P-values were corrected by FDR
Results
The cohort consisted mainly of males (95%) with a mean age of 53 years. The main ART was INSTIs-based (74% in LLV and 48% in SV). PWH groups showed a generalized higher level of soluble ICs over NHC, highlighting the IDO and Arginase-1 enzymes, as well as the members of the B7 (CD80 and PD-L1), CD28 (PD1 and BTLA), TNF/RSF (TNFRSF9), MHC-I (MICA and ULBP4), MACPF (Perforin-1) and Ig (LAG-3) superfamilies (Fig.1). They also revealed higher levels of the cardiometabolic markers NGAL, P-selectin, vWF and ST2. Compared to SV, LLV group showed a significant increase of sIDO, an immunosuppressive enzyme that inhibits effector T-cell functions and facilitates cell death through tryptophan degradation. They also showed a 1.4-fold increase of highly suppressive Treg FoxP3+Helios+ cells, targets also used for immune-oncology therapy. LLV also revealed higher levels of the subclinical atherosclerosis markers sICAM-1 and an upward trend of sCD14 (Fig.1)
Conclusions
PWH aged 50 years undergoing long-term ART showed increased soluble ICs, endothelial inflammation and hypercoagulable state, increasing the risk of cancer and CVD in the INSTI era. LLV favored an even more exacerbated immunosuppression environment, characterized by a marked increase in sIDO. This inhibitory molecule has been proposed as a prognostic marker for cancer and has also been linked to CVD, consistent with the elevation of Treg cells, sICAM-1 and sCD14 in LLV group. Our findings suggest that IDO could be a promising marker for early detection of future pathologies especially important in LLV population allowing rapid intervention