HIV-Associated Immune Activation and Persistent Inflammation

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Background

The diagnosis of HIV infection is challenging, particularly during the earliest stage which is defined as acute HIV infection (AHI) and is characterized by a negative or indeterminate HIV antibody (Ab) test in the presence of detectable HIV-1 RNA. The acute phase of HIV infection is associated with (i) high titre plasma viremia; (ii) dissemination of the virus to anatomical reservoirs such as the brain and (iii) establishment of a long-lived HIV reservoir in memory CD4+ T cells. The appearance of HIV Ab in the blood marks the transition to early phase HIV infection and a more stable level of plasma viremia (i.e. ‘set-point’ viremia) that serves as a prognostic factor of subsequent disease progression in the absence of anti-retroviral treatment (ART).

Current HIV treatment guidelines recommend immediate ART for all HIV-infected patients, including those with AHI. In fact, ART may be most beneficial when initiated during acute HIV infection, with individuals receiving early ART demonstrating: (i) more rapid and robust immunological recovery; (ii) lower levels of inflammation and (iii) reduced viral reservoir size compared to persons starting ART at later stages of infection.

Although ART has dramatically increased life expectancy and decreased morbidity, HIV-infected individuals still present with higher rates of aging-related non-AIDS disorders compared to HIV-uninfected persons. The major contributing factor is persistent, low-grade inflammation and immune activation which are strongly associated with several factors including: (i) heightened risk for cardiovascular disease; (ii) osteoporosis; (iii) anemia; (iv) physical function impairments and frailty, among other non-AIDS–defining events and mortality. In part, inflammation is driven by (i) HIV-associated destruction of mucosal immunity; (ii) CD8+ T cell-mediated enteropathy and (iii) subsequent translocation of microbes and microbe-derived moieties into the bloodstream.

Given the long-term consequences of chronic inflammation, there is an urgent need to better understand not only the causes and consequences of inflammation and immune activation in people living with HIV infection, but also protective factors, including the impact of early HIV diagnosis followed by immediate ART initiation.

In this Research Topic, we welcome the following manuscript types focusing on (early) diagnosis of HIV infection and/or inflammation in persons living with HIV: Original Research, Case Reports, Reviews, Mini-Reviews, Clinical Trials and Protocols. We particularly welcome articles reporting :

1. Novel diagnostic approaches for HIV.
2. Novel HIV screening strategies.
3. Novel biomarkers for prediction of non-AIDS disorders.
4. Mechanistic explanations that may inform development of interventions for prevention of non-AIDS disorders.

Keywords: Antiretroviral treatment, microbial translocation, non-AIDS events, immune activation, coagulation

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