Discordant Outcomes following Failure of Antiretroviral Therapy Are Associated with Substantial Differences in Human Immunodeficiency Virus-Specific Cellular Immunity

Abstract

؉ and CD8 ؉ T lymphocyte responses. In contrast, subjects with virologic failure associated with declining CD4 ؉ T lymphocyte counts had substantially weaker HIV-specific CD4 ؉ T lymphocyte responses and exhibited a trend towards weaker HIV-specific CD8 ؉ T lymphocyte responses. Importantly the CD4 ؉ response was sustained over periods as long as 11 months, confirming the stability of the phenomenon. These correlative data lead to the testable hypothesis that the consequences of viral recrudescence during continuous ART are modulated by the HIV-specific cellular immune response.

Preferential Infection Shortens the Life Span of Human ImmunodeficiencyVirus-Specific CD4+T Cells In Vivo

“…replicative capacity (10,30); in addition, transient boosting of CD4 ϩ T-cell responses to HIV Gag peptides has been observed after discontinuation of antiretroviral therapy (28). Overall, these observations suggest that an intimate balance prevails in vivo in which antigenic stimulation drives CD4 ϩ T-cell proliferation but is counteracted by destructive effects mediated by HIV.…”

The influence of depressive symptoms and substance use on adherence to antiretroviral therapy. A cross-sectional prevalence study

“…Since the viral load is a faster and more accurate method for signaling the clinical consequences of treatment failure 32 than the CD4+ cell count, which may be related to other immunological variations, 33 it is possible that a recent non-adherence pattern will also have the same ability, compared with past non-adherence. More importantly, since adherence does not provide a full explanation for the observed variations in treatment responses, 34 it was observed that the effect of non-adherence, as a consequence of missed doses, was related to growing levels of depressive symptoms.…”

Antiretroviral Drug Therapy Alters the Profile of Human Immunodeficiency Virus Type 1-Specific T-Cell Responses and Shifts the Immunodominant Cytotoxic T-Lymphocyte Response from Gag to Pol

“…This partial viral suppression is due in part to residual activity of antiretroviral drugs and reduced replicative capacity of the drug-resistant variants (6,13). We and others, however, have argued that drug treatment may exert pressure indirectly via the immune system (1,12,23,36,38). This interaction can occur via a number of non-mutually exclusive mechanisms, including treatment-mediated selection of new mutations that act as novel epitopes (23,(31)(32)(33)(39)(40)(41) and/or treatmentmediated decreases in replicative capacity ("fitness"), which can lead to a reduction in the ability of HIV-1 to destroy antigen-specific T cells (6,11,13,20).…”