Abstract

Treatment of HIV-infected patients with highly active antiretroviral therapy (HAART) usually results in diminished viral replication, increasing CD4+ cell counts, a reversal of most immunological disturbances, and a reduction in risk of morbidity and mortality. However, approximately 20% of all HIV-infected patients do not achieve optimal immune reconstitution despite suppression of viral replication. These patients are referred to as immunological nonresponders (INRs). INRs present with severely altered immunological functions, including malfunction and diminished production of cells within lymphopoetic tissue, perturbed frequencies of immune regulators such as regulatory T cells and Th17 cells, and increased immune activation, immunosenescence, and apoptosis. Importantly, INRs have an increased risk of morbidity and mortality compared to HIV-infected patients with an optimal immune reconstitution. Additional treatment to HAART that may improve immune reconstitution has been investigated, but results thus far have proved disappointing. The reason for immunological nonresponse is incompletely understood. This paper summarizes the known and unknown factors regarding the incomplete immune reconstitution in HIV infection, including mechanisms, relevance for clinical care, and possible solutions.

Highlights

  • Treatment of HIV infection with highly active antiretroviral therapy (HAART) usually results in diminished viral replication and increasing CD4+ cell counts

  • It is plausible that dysfunctions in one or more of these parameters contribute to the low CD4+ cell counts in immunological nonresponders (INRs)

  • INRs have higher levels of immune activation and apoptotic cells indicating a higher loss of CD4+ cells

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Summary

Introduction

Treatment of HIV infection with highly active antiretroviral therapy (HAART) usually results in diminished viral replication and increasing CD4+ cell counts. Approximately 20% of all HIV-infected individuals fail to restore their CD4+ cell counts despite optimal treatment and fully suppressed viral replication [2, 4, 5]. These individuals are referred to as immunological nonresponders (INRs). The increased risk of long-term morbidity and mortality in INR is widely accepted [11,12,13] This demonstrates an obvious reason for Clinical and Developmental Immunology delineating the cause of the poor immunological response seen in INR. The scope of this paper is to focus on the immunological explanations for immunological nonresponse in patients with full virological responses, clinical relevance, and feasible solutions

Explanations of Immunological Nonresponse
Clinical Implications
Therapeutical Possibilities
Findings
Conclusion and Future Directions
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