Dynamics of T Cells Subsets and Lymphoproliferative Responses During Structured Treatment Interruption Cycles and After Definitive Interruption of HAART in Early Chronic HIV Type-1-Infected Patients

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Abstract
Little is known about the consequences of short cycles of structured treatment interruption or definitive interruption of HAART for both T cell subset dynamics and T lymphoproliferative responses (LPR). Immunological follow-up was performed in 45 early chronical HIV-1-infected patients during short STI cycles during the first 12 weeks after the definitive interruption of HAART (DTI) and, thereafter, until VL reached a plateau. During STI cycles, CD8+, CD8+, CD28+, activation markers and naive CD4+ T cells increased significantly (p < 0.0001), while both naive CD8+ and memory CD4+ T cells decreased. During DTI, CD8+ CD28+ T cells fell and CD4+ naive T cells stabilized and the rest of the T cell subsets presented changes similar to those during STI cycles. Despite a transient increase in LPR to recall antigens and HIV proteins during STI cycles, LPR to polyclonal stimuli and pathogens decreased over the study. Differences in T cell subset dynamics and LPR observed throughout the study suggest that multiple exposures to low levels of antigen could improve the immune system, mainly by driving T cell maturation. Conversely, higher and longer viral replication after cessation of HAART overwhelms the immune system. These data may help to guide future immune-based therapies.