title: Incomplete immune recovery in HIV infection: mechanisms, relevance for clinical care, and possible solutions.
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.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Gaardbo
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Hartling
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Susanne D
authors.initials: SD
authors.lastname: Nielsen
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis / Q000276:immunology; D018791:CD4 Lymphocyte Count; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D015851:Interleukin-7 / Q000008:administration & dosage / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology / Q000821:virology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; D015851:Interleukin-7