Severe Immune Dysregulation Affects CD4+CD25hiFoxP3+ Regulatory T Cells in HIV-Infected Patients With Low-level CD4 T-Cell Repopulation Despite Suppressive Highly Active Antiretroviral Therapy

ABSTRACT The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection. In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4 T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells.

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The effect of tuberculosis on immune reconstitution among HIV patients on highly active antiretroviral therapy in Adigrat general hospital, eastern Tigrai, Ethiopia; 2019: a retrospective follow up study

BMC Immunology ◽

10.1186/s12865-019-0327-7 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Hadush Negash ◽

Haftom Legese ◽

Mebrahtu Tefera ◽

Fitsum Mardu ◽

Kebede Tesfay ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Cd4 T Cells ◽

Immune Reconstitution ◽

Cd4 T Cell ◽

Highly Active ◽

Cell Counts

Abstract Background Ethiopia initiated antiretroviral therapy early in 2005. Managing and detecting antiretroviral treatment response is important to monitor the effectiveness of medication and possible drug switching for low immune reconstitution. There is less recovery of CD4+ T cells among human immunodeficiency virus patients infected with tuberculosis. Hence, we aimed to assess the effect of tuberculosis and other determinant factors of immunological response among human immunodeficiency virus patients on highly active antiretroviral therapy. A retrospective follow up study was conducted from October to July 2019. A total of 393 participants were enrolled. An interviewer based questionnaire was used for data collection. Patient charts were used to extract clinical data and follow up results of the CD4+ T cell. Current CD4+ T cell counts of patients were performed. STATA 13 software was used to analyze the data. A p-value ≤0.05 was considered a statistically significant association. Results The mean age of study participants was 39.2 years (SD: + 12.2 years) with 8.32 mean years of follow up. The overall prevalence of immune reconstitution failure was 24.7% (97/393). Highest failure rate occurred within the first year of follow up time, 15.7 per 100 Person-year. Failure of CD4+ T cells reconstitution was higher among tuberculosis coinfected patients (48.8%) than mono-infected patients (13.7%). Living in an urban residence, baseline CD4+ T cell count ≤250 cells/mm3, poor treatment adherence and tuberculosis infection were significantly associated with the immunological failure. Conclusions There was a high rate of CD4+ T cells reconstitution failure among our study participants. Tuberculosis infection increased the rate of failure. Factors like low CD4+ T cell baseline count, poor adherence and urban residence were associated with the immunological failure. There should be strict monitoring of CD4+ T cell counts among individuals with tuberculosis coinfection.

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In HIV-infected patients, some differential alterations of CD4 and CD8 T cell homeostasis may not be restored by >=7 years of highly active antiretroviral therapy, in spite of good CD4 T cell repopulation

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dks099 ◽

2012 ◽

Vol 67 (7) ◽

pp. 1802-1804 ◽

Cited By ~ 3

Author(s):

V. Bordoni ◽

C. Agrati ◽

A. Rinaldi ◽

D. Viola ◽

G. De Simone ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Cd8 T Cell ◽

Cd4 T Cell ◽

T Cell Homeostasis ◽

Cell Homeostasis ◽

Highly Active ◽

Cell Repopulation

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Antigen-driven CD4+ T cell and HIV-1 dynamics: Residual viral replication under highly active antiretroviral therapy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.96.26.15167 ◽

1999 ◽

Vol 96 (26) ◽

pp. 15167-15172 ◽

Cited By ~ 51

Author(s):

N. M. Ferguson ◽

F. deWolf ◽

A. C. Ghani ◽

C. Fraser ◽

C. A. Donnelly ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Viral Replication ◽

Highly Active Antiretroviral Therapy ◽

Cd4 T Cell ◽

Highly Active ◽

Hiv 1

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Low-level plasma HIVs in patients on prolonged suppressive highly active antiretroviral therapy are produced mostly by cells other than CD4 T-cells

Journal of Medical Virology ◽

10.1002/jmv.21366 ◽

2008 ◽

Vol 81 (1) ◽

pp. 9-15 ◽

Cited By ~ 39

Author(s):

Gautam K. Sahu ◽

David Paar ◽

Simon D.W. Frost ◽

Melissa M. Smith ◽

Scott Weaver ◽

...

Keyword(s):

T Cells ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Cd4 T Cells ◽

Low Level ◽

Highly Active

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Interleukin-7 levels before highly active antiretroviral therapy may predict CD4+ T-cell recovery and virological failure in HIV-infected children

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkl032 ◽

2006 ◽

Vol 57 (4) ◽

pp. 798-800 ◽

Cited By ~ 8

Author(s):

Salvador Resino ◽

Alicia Pérez ◽

Juan Antonio León ◽

Mª Dolores Gurbindo ◽

Mª Ángeles Muñoz-Fernández

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Virological Failure ◽

Highly Active Antiretroviral Therapy ◽

Cd4 T Cell ◽

Cell Recovery ◽

Interleukin 7 ◽

Highly Active

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Persistence of Genital Tract T Cell Responses in HIV-Infected Women on Highly Active Antiretroviral Therapy

Journal of Virology ◽

10.1128/jvi.00518-10 ◽

2010 ◽

Vol 84 (20) ◽

pp. 10765-10772 ◽

Cited By ~ 9

Author(s):

Nonhlanhla N. Mkhize ◽

Pamela P. Gumbi ◽

Lenine J. Liebenberg ◽

Yuan Ren ◽

Peter Smith ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Genital Tract ◽

T Cell Responses ◽

Antiretroviral Drugs ◽

Cd4 T Cell ◽

Cell Responses ◽

Highly Active ◽

Cell Counts

ABSTRACT Initiation of highly active antiretroviral therapy (HAART) for HIV-infected individuals is associated with control of viremia, improved CD4 counts, and declining systemic HIV-specific immune responses. While HAART effectively reduces plasma viremia, it remains unclear how effectively antiretroviral drugs reach mucosal surfaces, such as those of the genital tract. The aim of this study was to determine the effect of HAART on genital tract CD4 T cell reconstitution, HIV shedding, and HIV-specific T cell responses. Cervical cytobrush and blood specimens were obtained from 35 HIV-infected, HAART-naïve women and 27 women on HAART in order to investigate HIV Gag-specific T cell responses by intracellular gamma interferon (IFN-γ) staining. Interleukin 1β (IL-1β), IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assays (ELISA). We show that for HIV-infected women, HAART is associated with significantly improved CD4 T cell counts both in blood and at the cervix. While HAART effectively suppressed both blood and cervical viremia, HIV-specific CD8 T cell responses in blood were lost, while those at the cervix were preserved.

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