HIV and inflammation: a new lead

Research. Despite the success of antiretroviral (ARV) treatment in controlling HIV infection and the possibility for people living with HIV (PLHIV) to live long and healthy lives, many of them (especially those who start ARV treatment following the onset of a chronic infection) have a stimulated immune system which leads to persistent inflammation in the body. Researchers have linked this inflammatory response to a higher incidence of various non-HIV comorbidities, including cardiovascular disease, diabetes and certain cancers, as well as mortality. The results of a recent study offer a new lead to solve part of the mystery of persistent inflammation in some PLHIV, reports the site Aidsmap. Although these results do not uncover a cause, they support the hypothesis that long-lasting inflammation is due to the inherited effects of chronic infection in untreated PHAs. To put it simply, the longer we wait before starting ARV treatment following an HIV infection, the greater the risk of having persistent inflammation in the body and therefore, as we age, of comorbidities unrelated to HIV. Hang on, the rest is not simple: interferons are proteins produced by the body following a viral infection. By attaching themselves to their target cells, these cytokines trigger various reactions allowing the establishment of a state of resistance to viruses. One potential mechanism that might explain how HIV-specific immunity promotes inflammation involves interferon-gamma, an antiviral cytokine. When T cells respond to pathogenic threats, they release this cytokine, which appears to activate macrophages — large cells with multiple immune functions, including releasing other cytokines that promote inflammation. To reach this conclusion, Dr. Adam Ward and his colleagues from Weill Medical College (New York, USA) analyzed data from a cohort of 99 people living with HIV who participated in the A5321 study of the Aids Clinical Trial Group (ACTG), which has studied HIV reservoirs in people on ARV treatment for a long time. All participants had experienced viraemic and chronic HIV before starting antiretroviral therapy. This means that at the time when they were not under treatment, they experienced a reactivation of HIV viral replication, following the exhaustion of the immune system’s control capacities. This increase in viremia induces a more rapid drop in CD4 lymphocytes. At the time of entry into the study, participants were on treatment and had maintained a viral load below 50 copies/ml for an average of seven years. The researchers point out that their analysis was limited to the production of interferon-gamma and did not take into account other HIV-specific T cell responses, which may play an important role in inflammation and immune activation. The study authors conclude that their findings support the theory that pathogenic mechanisms that occur before a person starts antiretroviral therapy are the primary drivers of immune dysregulation and therefore inflammation. If this theory turns out to be correct, it would provide an additional argument for enabling people living with HIV to access antiretroviral treatment as soon as possible following infection. Furthermore, understanding the mechanisms involved might lead to treatments that prevent or minimize inflammation, thereby improving the quality and length of life of PLHIV.