Ageing and inflammation in patients with HIV infection

Abstract

Summary Nowadays, HIV1 patients have an expected lifespan that is only slightly shorter than healthy individuals. For this reason, along with the fact that infection can be acquired at a relatively advanced age, the effects of ageing on HIV 1 people have begun to be evident. Successful anti-viral treatment is, on one hand, responsible for the development of side effects related to drug toxicity; on the other hand, it is not able to inhibit the onset of several complications caused by persistent immune activation and chronic inflammation. Therefore, patients with a relatively advanced age, i.e. aged more than 50 years, can experience pathologies that affect much older citizens. HIV 1 individuals with non-AIDS-related complications can thus come to the attention of clinicians because of the presence of neurocognitive disorders, cardiovascular diseases, metabolic syndrome, bone abnormalities and non-HIV-associated cancers. Chronic inflammation and immune activation, observed typically in elderly people and defined as 'inflammaging', can be present in HIV 1 patients who experience a type of premature ageing, which affects the quality of life significantly. This relatively new condition is extremely complex, and important factors have been identified as well as the traditional behavioural risk factors, e.g. the toxicity of anti-retroviral treatments and the above-mentioned chronic inflammation leading to a functional decline and a vulnerability to injury or pathologies. Here, we discuss the role of inflammation and immune activation on the most important non-AIDS-related complications of chronic HIV infection, and the contribution of aging per se to this scenario.

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

“…However, this therapy does not protect patients from the persistent immune activation, chronic inflammation, and excess risk of developing CVD and frailty 131–135 . Chronic inflammation in HIV is mediated by depletion of memory CD41 + T cells, resulting in increased permeability in the gut epithelium and translocation of microbial products into the circulation, which causes inflammation 136 .…”

Antiretroviral Treatment with Efavirenz Disrupts the Blood-Brain Barrier Integrity and Increases Stroke Severity

“…Nevertheless, these patients will likely be under treatment for the rest of their lives, meaning that they will be continually exposed to ARVd. Given the length of exposure, infected patients are at higher risk of developing co-morbidities, such as cardiovascular, metabolic and neurological disease34567. While some of these disorders can be attributed to HIV infection and the ensuing persistent state of inflammation, growing evidence indicates that ARVd toxicity could be at least partially involved in the development of these pathologies.…”

Invecchiamento cellulare e infezione da HIV

“…L'invecchiamento è accompagnato da uno stato di infiammazione cronica sistemica che contribuisce fortemente alla "frailty". Considerando le cellule T, la "frailty" è associata ad aumento di cellule TCD8+ con un fenotipo memoria proinfiammatorio che non esprimono il co-recettore CD28, ma esprimono CCR5 e presentano uno stato di senescenza replicativa (23). Rispetto ai disordini cognitivi gli effetti dell'infezione da HIV e l'età presentano un'azione sinergica; i pazienti HIV+ di 50 anni sono cognitivamente paragonabili a soggetti HIV negativi di 70-80 anni, presentando un deficit di memoria e di apprendimento (24).…”