Neurons in the hypothalamus, particularly the paraventricular nucleus, release vasopressin and corticotropin releasing hormone, which travel through the hypophysial portal vessel where they travel to and bind to the corticotropin-releasing hormone receptor on the anterior pituitary gland. Multiple CRH peptides have been identified, and receptors have been identified on multiple areas of the brain, including the amygdala. CRH is the main regulatory molecule of the release of ACTH.The secretion of ACTH into systemic circulation allows it to bind to and activate Melanocortin receptor, where it stimulates the release of steroid hormones. Steroid hormones bind to glucocorticoid receptors in the brain, providing negative feedback by reducing ACTH release. Some evidence supports a second long term feedback that is non-sensitive to cortisol secretion. The PVN of the hypothalamus receives inputs from the nucleus of the solitary tract, and lamina terminalis. Through these inputs, it receives and can respond to changes in blood.The PVN innervation from the brain stem nuclei, particularly the noradrenergic nuclei stimulate CRH release. Other regions of the hypothalamus both directly and indirectly inhibit HPA axis activity. Hypothalamic neurons involved in regulating energy balance also influence HPA axis activity through the release of neurotransmitters such as neuropeptide Y, which stimulates HPA axis activity. Generally, the amygdala stimulates, and the prefrontal cortex and hippocampus attenuate, HPA axis activity; however, complex relationships do exist between the regions.The immune system may be heavily influenced by stress. The sympathetic nervous system innervates various immunological structures, such as bone marrow and the spleen, allowing for it to regulate immune function.
This results in a change in immunological tolerance and the subsequent activation of abacavir-specific cytotoxic T cells, which produce a systemic reaction known as abacavir hypersensitivity syndrome. Interaction
Abacavir, and in general NRTIs, do not undergo hepatic metabolism and therefore have very limited (to none) interaction with the CYP enzymes and drugs that effect these enzymes. That being said there are still few interactions that can affect the absorption or the availability of abacavir. Below are few of the common established drug and food interaction that can take place during abacavir co-administration:

Protease inhibitors such as tipranavir or ritonovir may decrease the serum concentration of abacavir through induction of glucuronidation. Abacavir is metabolized by both alcohol dehydrogenase and glucuronidation. Ethanol may result in increased levels of abacavir through the inhibition of alcohol dehydrogenase. Abacavir is metabolized by both alcohol dehydrogenase and glucuronidation. Methadone may diminish the therapeutic effect of Abacavir. Abacavir may decrease the serum concentration of Methadone. Orlistat may decrease the serum concentration of antiretroviral drugs. The mechanism of this interaction is not fully established but it is suspected that it is due to the decreased absorption of abacavir by orlistat. Cabozantinib: Drugs from the MRP2 inhibitor (Multidrug resistance-associated protein 2 inhibitors) family such as abacavir could increase the serum concentration of Cabozantinib. Mechanism of action
Abacavir is a nucleoside reverse transcriptase inhibitor that inhibits viral replication. It is a guanosine analogue that is phosphorylated to carbovir triphosphate (CBV-TP). CBV-TP competes with the viral molecules and is incorporated into the viral DNA.