Mechanisms of Neuroimmune Interactions in Stress Physiology, Health Implications, and Emerging Therapeutic Targets.

Antiretroviral therapy (ART) has significantly improved the prognosis of people living with HIV by reducing morbidity and mortality, effectively transforming HIV into a manageable chronic disease. However, long-term ART use is associated with a range of metabolic disorders, particularly cardiovascular and endocrine complications, which contribute to increased non-AIDS-related morbidity and mortality. ART-induced dyslipidemia, insulin resistance, and lipodystrophy arise due to direct drug effects, chronic inflammation, mitochondrial toxicity, and alterations in lipid and glucose metabolism. Protease inhibitors and nucleoside reverse transcriptase inhibitors have been linked to dysregulation of hepatic cholesterol synthesis, increased triglyceride levels, and insulin resistance, promoting atherosclerosis and cardiovascular diseases. Additionally, ART impacts endocrine function, leading to thyroid dysfunction, adrenal insufficiency, osteoporosis, and hypogonadism. This is compounded by chronic immune activation and systemic inflammation in ART-treated individuals, which increases these metabolic disorders, creating a burden of non-communicable disease. While ART remains the cornerstone of HIV treatment, future research should focus on developing regimens that minimize metabolic toxicity while maintaining effective viral suppression. Addressing ART-relatedcomplications required proactive monitoring, individualized treatment, and lifestyle modifications to enhance the long-term quality of life and overall health of individuals on HIV therapy.