Cardiovascular disease (CVD) risk assessment of HIV medication regimens using hematopoietic CD34+ progenitor cells

Abstract

Background To determine the effects of integrase inhibitor (INSTI) in comparison with non-INSTI-based regimens such as non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based regimens on cardiovascular disease (CVD) risk in HIV+ patients without overt history of CVD or diabetes, with normal CD4:CD8 count. For CVD risk assessment we primarily used hematopoietic CD34+ progenitor cells, as a biomarker. Methods Nineteen male subjects, ages 32–61 years with BMI 21.0–36.0, were enrolled. This was a single time point, cross-sectional, observational study. Subjects were enrolled under 2 groups (either on INSTI-based regimen with 13 subjects or NNRTI (non-INSTI)-based regimens with 6 subjects) who were taking stable doses of HAART. The medication regimens were a combination of one NRTI (typically tenofovir–emtricitabine) plus one INSTI or NNRTI. Our outcome measures were focused on cardiovascular and endothelial cell function and systemic inflammation. Our primary outcome measures were peripheral blood-derived hematopoietic progenitor cell number (CD34 and CD133 positive), CD34+ cell function and gene expression studies. Our secondary outcomes were arterial stiffness measures and serum-based markers of inflammation. Results A significant increase in percentage number of progenitor cells, CD133+ cells (p = 0.004), was noted along with an increase of double progenitor mark positive CD133+/CD34+ progenitor cell population being observed in INSTI group as compared to NNRTI group, by flow cytometry. mRNA gene expression for antioxidant gene catalase was noted along with a trend toward a decrease in gene expression of inflammatory marker IL6 (p = 0.06) being observed in CD34+ from INSTI group vs NNRTI group. The plasma IL-6 and CRP levels did not change significantly between the groups. Neutrophil–Lymphocyte ratio (NLR), an important marker of inflammation, was noted to be lower in INSTI group. A mean fasting glucose level was also lower in the INSTI group compared to NNRTI group (p = 0.03). Interestingly, urine microalbumin levels were higher in the INSTI group compared to NNRTI group (p = 0.08), while eGFR levels were significantly lower in the INSTI group (p = 0.002). The arterial stiffness measures did not show statistically significant differences between the two groups. Conclusion We conclude that the INSTI regimen may provide a better CVD risk profile compared to NNRTI-based HAART regimen; however, the increased albuminuria along with lower eGFR, noted in INSTI group, is of concern. Because of the small size, these results would need replication in additional studies before changing clinical practice. Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03782142?cond=Hiv&spons=Sabyasachi+sen&cntry=US&state=US%3ADC&city=Washington&draw=2&rank=1. ClinicalTrials.gov Identifier: NCT03782142.

Sex differences in incident atherosclerotic cardiovascular disease events among women and men with HIV

“…Further, the availability of objective HIV-specific factors (i.e., viral load and CD4 þ cell count) would have provided clarity as to the impact of HIV-specific factors on ASCVD risk, and if these vary by sex [18,21]. Additionally, although it is now well documented than INSTIs are associated with better cardiovascular risk profiles compared to other classes of ART, INSTIs were not the preferred line of drug during the entire time 2011-2019 time period, which limits our ability to detect sex-based differences in ASCVD risk associated with drug class [30][31][32]. Although we were able to examine the relationships between age and ASCVD risk among WLHIV, we did not have data on menopausal status, which would have provided further insight into the mechanisms influencing sex-specific ASCVD risk among PWH [18,33,34].…”

Circulating Endothelial Progenitor and Mesenchymal Stromal Cells as Biomarkers for Monitoring Disease Status and Responses to Exercise

“…EPCs can act as a cellular biomarker that is more reliable than commonly used clinical serum-based markers for estimating and following endothelial dysfunction in aging, early T2D and prediabetes subjects, pre-and postexercise, and even in response to medications [44][45][46][47][48][49][50][51]. Older adults are shown to have lower baseline levels of HSC, EPC, angiogenic T cells, as well as chemokine receptor 4 expressing circulating angiogenic cells (CXCR4expressing CACs) [52][53][54][55].…”