Immune Reconstitution in HIV‐Infected Patients

Abstract

The prognosis of patients infected with human immunodeficiency virus (HIV) type 1 has dramatically improved since the advent of potent antiretroviral therapies (ARTs), which have enabled sustained suppression of HIV replication and recovery of CD4 T cell counts. Knowledge of the function of CD4 T cells in immune reconstitution was derived from large clinical studies demonstrating that primary and secondary prophylaxis against infectious agents, such as Pneumocystis jirovecii (Pneumocystis carinii), Mycobacterium avium complex, cytomegalovirus, and other pathogens, can be discontinued safely once CD4 T cell counts have increased beyond pathogen-specific threshold levels (usually >200 CD4 T cells/mm3) for 3-6 months. The downside of immune reconstitution is an inflammatory syndrome occurring days to months after the start of ART, with outcomes ranging from minimal morbidity to fatal progression. This syndrome can be elicited by infectious and noninfectious antigens. Microbiologically, the possible pathogenic pathways involve recognition of antigens associated with ongoing infection or recognition of persisting antigens associated with past (nonreplicating) infection. Specific antimicrobial therapy, nonsteroidal anti-inflammatory drugs, and/or steroids for managing immune reconstitution syndrome should be considered.

Histological Patterns of Polyomavirus Nephropathy: Correlation with Graft Outcome and Viral Load

“…secondary to tubular injury). Excessive tissue destruction may occur once the immune system recovers its capabilities (immune reconstitution response) (28,(33)(34)(35). Irrespective of the underlying etiopathogenesis, florid inflammatory responses in PVAN are often associated with parenchymal fibrosis (scarring) (9,29).…”

Soft tissue abscess and lymphadenitis due to Mycobacterium avium Complex as an expression of immune reconstitution inflammatory syndrome after a second scheme of highly active antiretroviral therapy

“…IRIS is an inflammatory reaction which appears after initiating or changing of HAART regimens and is temporally related with an increase in the CD4 + T-cell counts 3,8 .…”

“…Treatment for this complication of AIDS therapy includes the continuation of primary therapy against the pathogen implicated in the IRIS to decrease the antigenic load, the continuation of HAART and, eventually, the use of non-steroid antiinflammatory agents and corticosteroids 8,17 . IRIS is a condition thought to be caused by the improvement in the host's immune response to several pathogens.…”

Combination antifungal therapy: what can and should we expect?

“…However, restoration of host immunity using immunomodulators such as G-CSF, GM-CSF or HAART carries the risk of immune reconstitution inflammatory syndrome and clinical presentations mimicking antifungal drug failure. [7][8][9][10][11][12][13] Clearly, all immunodeficiency is not created equal, so a one-size-fits-all approach to immunomodulator therapy will probably not work. 7 Individualized approaches are likely necessary to restore the appropriate balance to any given host and maximize chances of successful outcome with antifungal drug therapy.…”