Intrinsic Apoptotic Pathway Genes of Circulating Blood Neutrophils Triggered during HIV Infection and Remained Stimulated in ART Patients

Background: The intrinsic apoptotic pathway of neutrophils in Human Immunodeficiency Virus (HIV) infection results in spontaneous neutrophil death. There is a scarcity of data regarding the gene expression of an intrinsic apoptotic pathway of neutrophils in HIV patients. Objective: The objective of this study was to observe the differential expression of some important genes involved in the intrinsic apoptotic pathway of HIV patients, including those who were receiving antiretroviral therapy (ART). Methods: Blood samples were collected from asymptomatic, symptomatic, ART receiver HIV patients, and healthy individuals. Total RNA was extracted from neutrophils and subjected to quantitative real-time PCR assay. CD4⁺T cells and an automated complete blood count were performed. Results: Among the asymptomatic, symptomatic, and ART receiver HIV patients (n=20 in each group), median CD4⁺T counts were 633, 98, and 565 cells/ml, and the length of HIV infection in months (± SD) was 24.06 ± 21.36, 62.05 ± 25.51, and 69.2 ± 39.67, respectively. Compared with healthy controls, intrinsic apoptotic pathway genes, i.e., BAX, BIM, Caspase-3, Caspase-9, MCL-1, and Calpain-1, were upregulated to 1.21 ± 0.33, 1.8 ± 0.25, 1.24 ± 0.46, 1.54 ± 0.21, 1.88 ± 0.30, and 5.85 ± 1.34 fold in the asymptomatic group, and even more significantly, i.e., 1.51 ± 0.43, 2.09 ± 1.13, 1.85 ± 1.22, 1.72 ± 0.85, 2.26 ± 1.34, and 7.88 ± 3.31 fold in symptomatic patients, respectively. Despite CD4⁺ T-cell levels increased in the ART receiver group, these genes did not approach the level of healthy or asymptomatic and remained significantly upregulated. Conclusion: The genes involved in the intrinsic apoptotic pathway in circulating neutrophils during HIV infection were stimulated in vivo, and ART reduced the expression of those upregulated genes but did not return to the level of asymptomatic or healthy individuals.