Immunodiscordant responses to HAART – mechanisms and consequences

Abstract

A relevant fraction of HIV-1-infected individuals (ranging from 15 to 30%) presenting virologically successful highly active antiretroviral therapy fail to recover CD4 T-cell counts. These individuals, called immunodiscordant or immunological nonresponders, are at increased risk of clinical progression and death. Although older age, lower nadir CD4 T-cell count and HCV co-infection are some of clinical predictive factors, immunological mechanisms rely on impaired thymic production and accumulation of apoptosis-prone CD4 T cells. Indeed, immunodiscordant individuals may show increased tissue fibrosis and damage of gut-associated lymphoid tissue that results in higher hyperactivation, inflammation and immunosenescence, altered Treg/Th17 ratio and increased T-cell death. A better knowledge of the final pathogenic mechanism and factors influencing CD4 T-cell recovery will help to select the optimal therapeutic strategies for them.

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

“…The duration of ART can significantly affect the magnitude of immune reconstitution in HIV‐1‐infected patients, thus hindering the comparison of different findings. According to the heterogeneity among study populations and discrepancy in definitions, the prevalence of INRs varies from 10% to 40% . In contrast, an adequate immune response to ART is defined as CD4 + T‐cell counts >500 cells/µl, mainly because HIV‐1‐infected patients with this level of immune restoration have a morbidity and mortality rate approaching or comparable to those of HIV negative individuals .…”

“…According to the heterogeneity among study populations and discrepancy in definitions, the prevalence of INRs varies from 10% to 40%. 7,14,15 In contrast, an adequate immune response to ART is defined as CD4 + T-cell counts >500 cells/µl, mainly because HIV-1-infected patients with this level of immune restoration have a morbidity and mortality rate approaching or comparable to those of HIV negative individuals. 13,[16][17][18] In addition, the Department of Health and Human Services (DHHS) considered that patients with CD4 + T-cell counts that had not increased to 350-500 cells/µl after 4-7 years of effective ART were defined as INRs.…”

“…1). 14,[23][24][25] However, none of these independent factors can fully explain the mechanism of incomplete immune reconstitution. At any time, the CD4 + T-cell counts in HIV-1-infected individuals are associated with the production, destruction, and migration between secondary lymphoid organs and peripheral tissues.…”

New signatures of poor CD4 cell recovery after suppressive antiretroviral therapy in HIV-1-infected individuals: involvement of miR-192, IL-6, sCD14 and miR-144

“…IL-2 therapy, although it resulted in CD4 count increases 8 . The use of other immune-based therapies (e.g., growth hormones or IL-7) is controversial and its clinical benefit remains unclear 9 .…”

Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy

“…HIV infection results in defects in cell-mediated immunity, B cell dysfunction, loss of memory B cell subset, and suboptimal humoral immune responses, [1][2][3][4][5][6][7] which increase the vulnerability of HIV-infected patients to acquire Streptococcus pneumoniae infection. In addition, older age, coinfection with hepatitis viruses, co-morbidities, cigarette smoking, and substance abuse are also associated with an increased risk of pneumococcal pneumonia and/or invasive pneumococcal disease (IPD), defined as isolation of S. pneumoniae from a normally sterile site such as blood, cerebrospinal fluid or pleural fluid, while antiretroviral therapy, influenza vaccination and antibiotic prophylaxis are associated with a decreased risk.…”