+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells

Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells

Journal of Infectious Diseases 204(8): 1217-1226

Failure to normalize CD4(+) T-cell numbers despite effective antiretroviral therapy is an important problem in human immunodeficiency virus (HIV) infection. To evaluate potential determinants of immune failure in this setting, we performed a comprehensive immunophenotypic characterization of patients with immune failure despite HIV suppression, persons who experienced CD4(+) T-cell restoration with therapy, and healthy controls. Profound depletion of all CD4(+) T-cell maturation subsets and depletion of naive CD8(+) T cells was found in immune failure, implying failure of T-cell production/expansion. In immune failure, both CD4(+) and CD8(+) cells were activated but only memory CD4(+) cells were cycling at increased frequency. This may be the consequence of inflammation induced by in vivo exposure to microbial products, as soluble levels of the endotoxin receptor CD14(+) and interleukin 6 were elevated in immune failure. In multivariate analyses, naive T-cell depletion, phenotypic activation (CD38(+) and HLA-DR expression), cycling of memory CD4(+) T cells, and levels of soluble CD14 (sCD14) distinguished immune failure from immune success, even when adjusted for CD4(+) T-cell nadir, age at treatment initiation, and other clinical indices. Immune activation that appears related to exposure to microbial elements distinguishes immune failure from immune success in treated HIV infection.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 053704337

Download citation: RISBibTeXText

PMID: 21917895

DOI: 10.1093/infdis/jir507

Related references

Plasma Biomarkers of Human Immunodeficiency Virus-Related Systemic Inflammation and Immune Activation in Sub-Saharan Africa Before and During Suppressive Antiretroviral Therapy. Journal of Infectious Diseases 220(6): 1029-1033, 2019

CD8+ T-memory stem cells maintain the capacity for a cellular immune response against HIV-1 in patients on suppressive antiretroviral therapy. Aids 29(15): N11, 2015

Maraviroc Is Associated with Latent HIV-1 Reactivation through NF-κB Activation in Resting CD4 + T Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy. Journal of Virology 92(9):, 2018

Monitoring of HIV type 1 DNA load and drug resistance in peripheral blood mononuclear cells during suppressive antiretroviral therapy does not predict virologic failure. Aids Research and Human Retroviruses 28(8): 780-788, 2012

Immunologic, virologic, and clinical consequences of episodes of transient viremia during suppressive combination antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes 48(1): 104-108, 2008

Virologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4+ T-cell recovery. Aids 29(16): 2121-2129, 2015

Pathological Role of Anti-CD4 Antibodies in HIV-Infected Immunologic Nonresponders Receiving Virus-Suppressive Antiretroviral Therapy. Journal of Infectious Diseases 216(1): 82-91, 2017

Tumor necrosis factor (TNF) system levels in human immunodeficiency virus-infected patients during highly active antiretroviral therapy: persistent TNF activation is associated with virologic and immunologic treatment failure. Journal of Infectious Diseases 179(1): 74-82, 1998

Effect of Antiretroviral Therapy on the Memory and Activation Profiles of B Cells in HIV-Infected African Women. Journal of Immunology 198(3): 1220-1228, 2017

Suppressive effect of normal lymphoid cells on manifestations of immunologic memory. Zhurnal Mikrobiologii Epidemiologii i Immunobiologii 1978(3): 20-23, 1978

The impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy. Aids 27(13): 2101-2110, 2013

Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. Plos Pathogens 10(10): E1004473, 2014

Predicting treatment failure in adults and children on antiretroviral therapy: a systematic review of the performance characteristics of the 2010 WHO immunologic and clinical criteria for virologic failure. Aids 28(Suppl. 2): S161-S169, 2014

Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy. Journal of Infectious Diseases 202(10): 1553-1561, 2010

No virological failure in semen during properly suppressive antiretroviral therapy despite subtherapeutic local drug concentrations. HIV Clinical Trials 7(6): 285-290, 2007