Suppression of HIV-1 plasma viral load below detection preserves IL-17 producing T cells in HIV-1 infection

Background. Highly active antiretroviral therapy induces clinical benefits to HIV-1 infected individuals, which can be striking in those with progressive disease. Improved survival and decreased incidence of opportunistic infections go hand in hand with a suppression of the plasma viral load, an increase in peripheral CD4+ T-cell counts, as well as a reduction in the activation status of both CD4+ and CD8+ T cells.Methods. We investigated T-cell dynamics during ART by polychromatic flow cytometry in total as well as in HIV-1-specific CD4+ and CD8+ T cells. We also measured gene expression by single cell transcriptomics to assess functional state.Results. The cytokine pattern of HIV-specific CD8+ T cells was not altered after ART, though their magnitude decreased significantly as the plasma viral load was suppressed to undetectable levels. Importantly, while CD4+ T cell numbers increased substantially during the first year, the population did not normalize: the increases were largely due to expansion of mucosal-derived CCR4+ CD4+ TCM; transcriptomic analysis revealed that these are not classical Th2-type cells.Conclusion. The apparent long-term normalization of CD4+ T-cell numbers following ART does not comprise a normal balance of functionally distinct cells, but results in a dramatic Th2 shift of the reconstituting immune system.

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Faculty Opinions recommendation of Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14292.471794 ◽

2006 ◽

Author(s):

Ann Duerr

Keyword(s):

Viral Load ◽

High Risk ◽

Plasma Viral Load ◽

African Women ◽

Set Point ◽

Acute Hiv ◽

Hiv Type 1 ◽

Hiv 1

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Proviral HIV-1 DNA in subjects followed since primary HIV-1 infection who suppress plasma viral load after one year of highly active antiretroviral therapy

AIDS ◽

10.1097/00002030-200104130-00001 ◽

2001 ◽

Vol 15 (6) ◽

pp. 665-673 ◽

Cited By ~ 88

Author(s):

Nicole Ngo-Giang-Huong ◽

Christiane Deveau ◽

Isabelle Da Silva ◽

Isabelle Pellegrin ◽

Alain Venet ◽

...

Keyword(s):

Viral Load ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Plasma Viral Load ◽

Highly Active ◽

One Year ◽

Hiv 1

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Spontaneous HIV-1 replication in a B-lymphoblastoid cell line obtained from an HIV-1-positive patient with undetectable plasma viral load

AIDS ◽

10.1097/01.aids.0000232248.81780.ec ◽

2006 ◽

Vol 20 (9) ◽

pp. 1340-1342

Author(s):

Liliana Belmonte ◽

Cecilia Parodi ◽

Patricia Bare ◽

Marcelo Corti ◽

Norberto Sanjuan ◽

...

Keyword(s):

Viral Load ◽

Cell Line ◽

Plasma Viral Load ◽

Lymphoblastoid Cell Line ◽

Positive Patient ◽

Undetectable Plasma ◽

Undetectable Plasma Viral Load ◽

Hiv 1

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Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ TEMRA Cells in Early Infection Are Linked to Control of HIV-1 Viremia and Predict the Subsequent Viral Load Set Point

Journal of Virology ◽

10.1128/jvi.00045-07 ◽

2007 ◽

Vol 81 (11) ◽

pp. 5759-5765 ◽

Cited By ~ 52

Author(s):

John W. Northfield ◽

Christopher P. Loo ◽

Jason D. Barbour ◽

Gerald Spotts ◽

Frederick M. Hecht ◽

...

Keyword(s):

T Cells ◽

Viral Load ◽

T Cell ◽

Absolute Number ◽

T Cell Response ◽

Effector Memory ◽

Set Point ◽

Effector Memory T Cells ◽

Viral Load Set Point ◽

Hiv 1

ABSTRACT CD8+ T cells are believed to play an important role in the control of human immunodeficiency virus type 1 (HIV-1) infection. However, despite intensive efforts, it has not been possible to consistently link the overall magnitude of the CD8+ T-cell response with control of HIV-1. Here, we have investigated the association of different CD8+ memory T-cell subsets responding to HIV-1 in early infection with future control of HIV-1 viremia. Our results demonstrate that both a larger proportion and an absolute number of HIV-1-specific CD8+ CCR7− CD45RA+ effector memory T cells (TEMRA cells) were associated with a lower future viral load set point. In contrast, a larger absolute number of HIV-1-specific CD8+ CCR7− CD45RA− effector memory T cells (TEM) was not related to the viral load set point. Overall, the findings suggest that CD8+ TEMRA cells have superior antiviral activity and indicate that both qualitative and quantitative aspects of the CD8+ T-cell response need to be considered when defining the characteristics of protective immunity to HIV-1.

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Dynamics and Correlates of CD8 T-Cell Counts in Africans with Primary Human Immunodeficiency Virus Type 1 Infection

Journal of Virology ◽

10.1128/jvi.01467-16 ◽

2016 ◽

Vol 90 (22) ◽

pp. 10423-10430 ◽

Cited By ~ 1

Author(s):

Heather A. Prentice ◽

Hailin Lu ◽

Matthew A. Price ◽

Anatoli Kamali ◽

Etienne Karita ◽

...

Keyword(s):

T Cells ◽

Viral Load ◽

T Cell ◽

Human Leukocyte ◽

Neutralizing Antibody ◽

Sensitivity Analyses ◽

Supporting Evidence ◽

Cell Counts ◽

Cellular And Humoral Immunity ◽

Hiv 1

ABSTRACT In individuals with HIV-1 infection, depletion of CD4 + T cells is often accompanied by a malfunction of CD8 + T cells that are persistently activated and/or exhausted. While the dynamics and correlates of CD4 counts have been well documented, the same does not apply to CD8 counts. Here, we examined the CD8 counts in a cohort of 497 Africans with primary HIV-1 infection evaluated in monthly to quarterly follow-up visits for up to 3 years in the absence of antiretroviral therapy. Statistical models revealed that (i) CD8 counts were relatively steady in the 3- to 36-month period of infection and similar between men and women; (ii) neither geography nor heterogeneity in the HIV-1 set-point viral load could account for the roughly 10-fold range of CD8 counts in the cohort ( P > 0.25 in all tests); and (iii) factors independently associated with relatively high CD8 counts included demographics (age ≤ 40 years, adjusted P = 0.010) and several human leukocyte antigen class I (HLA-I) alleles, including HLA-A*03:01 ( P = 0.013), B*15:10 ( P = 0.007), and B*58:02 ( P < 0.001). Multiple sensitivity analyses provided supporting evidence for these novel relationships. Overall, these findings suggest that factors associated with the CD8 count have little overlap with those previously reported for other HIV-1-related outcome measures, including viral load, CD4 count, and CD4/CD8 ratio. IMPORTANCE Longitudinal data from 497 HIV-1 seroconverters allowed us to systematically evaluate the dynamics and correlates of CD8 + T-cell counts during untreated primary HIV-1 infection in eastern and southern Africans. Our findings suggest that individuals with certain HLA-I alleles, including A*03 (exclusively A*03:01), persistently maintain relatively high CD8 counts following HIV-1 infection, a finding which may offer an intriguing explanation for the recently reported, negative association of A*03 with HIV-1-specific, broadly neutralizing antibody responses. In future studies, attention to HLA-I genotyping data may benefit in-depth understanding of both cellular and humoral immunity, as well as the intrinsic balances of these types of immunity, especially in settings where there is emerging evidence of antagonism between the two arms of adaptive immunity.

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