Residual Immune Dysregulation Syndrome in Treated HIV infection

Abstract

Antiretroviral therapy has revolutionized the course of HIV infection, improving immune function and decreasing dramatically the mortality and morbidity due to the opportunistic complications of the disease. Nonetheless, even with sustained suppression of HIV replication, many HIV-infected persons experience a syndrome characterized by increased T cell activation and evidence of heightened inflammation and coagulation. This residual immune dysregulation syndrome or RIDS is more common in persons who fail to increase circulating CD4+ T cells to normal levels and in several epidemiologic studies it has been associated with increased morbidity and mortality. These morbid and fatal events are not the typical opportunistic infections and malignancies seen in the early AIDS era but rather comprise a spectrum of cardiovascular events, liver disease, metabolic disorders, kidney disease, bone disease, and a spectrum of malignant complications distinguishable from the opportunistic malignancies that characterized the earlier days of the AIDS epidemic. While immune activation, inflammation, and coagulopathy are characteristic of untreated HIV infection and improve with drug-induced control of HIV replication, the drivers of RIDS in treated HIV infection are incompletely understood. And while inflammation, immune activation, and coagulopathy are more common in treated persons who fail to restore circulating CD4+ T cells, it is not entirely clear how these two phenomena are linked.

Inflammatory Function of CX3CR1+CD8+T Cells in Treated HIV Infection Is Modulated by Platelet Interactions

“…Indices of inflammation and coagulation are heightened in ART-suppressed HIV-infected persons, particularly in patients with suboptimal CD4 + T-cell reconstitution [39,40], and these indices predict cardiovascular risk [41,42]. Circulating immune cells can interact with soluble coagulation elements through expression of the thrombin receptor PAR-1.…”

Association of CMV, HBV, or HCV co-infection with vaccine response in adults with well-controlled HIV infection

“…Other possible etiologies for the suboptimal vaccine response seen in adults with well-controlled HIV infection include residual immune dysfunction from the initial HIV infection, and/or chronic immune activation from HIV infection itself. 33 In addition, the CD4 count normal range, generally defined as 500-1500 cells/mm 3 , may be too broad. A recent study found that the median CD4 count in HIV-uninfected subjects was 900 cells/mm 3 , and that HIV-infected subjects who started antiretroviral therapy earlier were both more likely to achieve CD4 counts >900 cells/mm 3 , and more likely to respond to HBV vaccination.…”

Understanding Interferon Subtype Therapy for Viral Infections: Harnessing the Power of the Innate Immune System.

“…In humanised mice, the human IFN-α14 subtype was more potent than IFN-α2 in antiviral activity when used in postexposure prophylaxis and treatment of acute viral infection with better regulation of immune hyperactivation [55]. Distinct from IFN-α2, which elicited higher As seen in the clinical HIV-1 setting, systemic immune activation via IFN stimulation of monocytes is a hallmark characteristic regardless of successful anti-retroviral treatment in suppressing plasma levels of HIV RNA [56,57]. In fact, HIV-1-induced immune hyperactivation is associated with increased prevalence and earlier onset of co-morbidities (cognitive decline, diabetes, liver disease, cardiovascular disease), signifying disease progression in HIV-1 patients.…”