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Immunologic and Virologic Progression in HIV Controllers: The Role of Viral "Blips" and Immune Activation in the ANRS CO21 CODEX Study.

Noel N, Lerolle N, Lécuroux C, Goujard C, Venet A, Saez-Cirion A, Avettand-Fenoël V, Meyer L, Boufassa F, Lambotte O, ANRS C021 CODEX Study Gro - PLoS ONE (2015)

Bottom Line: Disease progression was observed in 15 of the 217 patients followed up between 2009 and 2013 (ImmP, n = 10; VirP, n = 5).T cell activation and IP10 levels at inclusion were significantly higher in ImmP than in non-progressors.These factors should be considered for adjusting their follow-up.

View Article: PubMed Central - PubMed

Affiliation: UMR 1184, Immunologie des Maladies Virales et Autoimmunes (IMVA), Université Paris Sud, Le Kremlin Bicêtre, France; Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France.

ABSTRACT
Some HIV controllers (HICs) experience CD4+T cell count loss and/or lose their ability to control HIV. In this study, we investigated the rate of immunologic and/or virologic progression (ImmP/VirP) and its determinants in the ANRS CO21/CODEX cohort. Immunologic progression was defined as a lasting fall in CD4+T cell count below 350/mm(3) or more than 200/mm(3) with a baseline count below 600/mm(3). Virologic progression was defined as a HIV viral load (VL) above 2000 copies/mL on two consecutive determinations. Clinical characteristics, immune activation, ultrasensitive HIV VL and total HIV DNA were analyzed. Disease progression was observed in 15 of the 217 patients followed up between 2009 and 2013 (ImmP, n = 10; VirP, n = 5). Progressors had higher ultrasensitive HIV RNA levels at inclusion (i.e. 1-2 years before progression) than non-progressors. ImmP had also lower CD4+T cell nadir and CD4+T cell count at inclusion, and VirP had higher HIV DNA levels in blood. T cell activation and IP10 levels at inclusion were significantly higher in ImmP than in non-progressors. In summary, the lasting loss of CD4+T cells, residual HIV replication and basal levels of immune activation appear to be major determinants of progression in HICs. These factors should be considered for adjusting their follow-up.

No MeSH data available.


Related in: MedlinePlus

Comparison of immune activation parameters in immunologic or virologic progressor HICs, non-progressor HICs, ART-treated patients, chronic viremic patients and healthy donors.(A) Proportion of activated circulating HLA-DR+CR38+ CD4+ T cells. (B) Proportion of activated circulating HLA-DR+CD38+ CD8+ T cells. (C) Plasma IP10 levels (pg/mL, logarithmic scale).
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pone.0131922.g002: Comparison of immune activation parameters in immunologic or virologic progressor HICs, non-progressor HICs, ART-treated patients, chronic viremic patients and healthy donors.(A) Proportion of activated circulating HLA-DR+CR38+ CD4+ T cells. (B) Proportion of activated circulating HLA-DR+CD38+ CD8+ T cells. (C) Plasma IP10 levels (pg/mL, logarithmic scale).

Mentions: Lastly, we determined whether or not markers of immune activation/inflammation at inclusion were predictive of progression. As shown in Fig 2, the proportion of activated circulating CD8+ and CD4+ T cells (as defined by the expression of both HLA-DR and CD38 surface antigens) were higher in immunologic progressors than in non-progressors at inclusion in the cohort. In patients with virologic progression, only the proportion of activated CD8+ T cells was significantly higher. Interestingly, the proportion of activated T cells was (i) as elevated in progressor HICs as in viremic patients, and (ii) as low in non-progressor HICs as in ART-treated patients (Fig 2).


Immunologic and Virologic Progression in HIV Controllers: The Role of Viral "Blips" and Immune Activation in the ANRS CO21 CODEX Study.

Noel N, Lerolle N, Lécuroux C, Goujard C, Venet A, Saez-Cirion A, Avettand-Fenoël V, Meyer L, Boufassa F, Lambotte O, ANRS C021 CODEX Study Gro - PLoS ONE (2015)

Comparison of immune activation parameters in immunologic or virologic progressor HICs, non-progressor HICs, ART-treated patients, chronic viremic patients and healthy donors.(A) Proportion of activated circulating HLA-DR+CR38+ CD4+ T cells. (B) Proportion of activated circulating HLA-DR+CD38+ CD8+ T cells. (C) Plasma IP10 levels (pg/mL, logarithmic scale).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493076&req=5

pone.0131922.g002: Comparison of immune activation parameters in immunologic or virologic progressor HICs, non-progressor HICs, ART-treated patients, chronic viremic patients and healthy donors.(A) Proportion of activated circulating HLA-DR+CR38+ CD4+ T cells. (B) Proportion of activated circulating HLA-DR+CD38+ CD8+ T cells. (C) Plasma IP10 levels (pg/mL, logarithmic scale).
Mentions: Lastly, we determined whether or not markers of immune activation/inflammation at inclusion were predictive of progression. As shown in Fig 2, the proportion of activated circulating CD8+ and CD4+ T cells (as defined by the expression of both HLA-DR and CD38 surface antigens) were higher in immunologic progressors than in non-progressors at inclusion in the cohort. In patients with virologic progression, only the proportion of activated CD8+ T cells was significantly higher. Interestingly, the proportion of activated T cells was (i) as elevated in progressor HICs as in viremic patients, and (ii) as low in non-progressor HICs as in ART-treated patients (Fig 2).

Bottom Line: Disease progression was observed in 15 of the 217 patients followed up between 2009 and 2013 (ImmP, n = 10; VirP, n = 5).T cell activation and IP10 levels at inclusion were significantly higher in ImmP than in non-progressors.These factors should be considered for adjusting their follow-up.

View Article: PubMed Central - PubMed

Affiliation: UMR 1184, Immunologie des Maladies Virales et Autoimmunes (IMVA), Université Paris Sud, Le Kremlin Bicêtre, France; Assistance Publique-Hôpitaux de Paris, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud, Le Kremlin-Bicêtre, France; Faculté de Médecine Paris Sud, Le Kremlin Bicêtre, France.

ABSTRACT
Some HIV controllers (HICs) experience CD4+T cell count loss and/or lose their ability to control HIV. In this study, we investigated the rate of immunologic and/or virologic progression (ImmP/VirP) and its determinants in the ANRS CO21/CODEX cohort. Immunologic progression was defined as a lasting fall in CD4+T cell count below 350/mm(3) or more than 200/mm(3) with a baseline count below 600/mm(3). Virologic progression was defined as a HIV viral load (VL) above 2000 copies/mL on two consecutive determinations. Clinical characteristics, immune activation, ultrasensitive HIV VL and total HIV DNA were analyzed. Disease progression was observed in 15 of the 217 patients followed up between 2009 and 2013 (ImmP, n = 10; VirP, n = 5). Progressors had higher ultrasensitive HIV RNA levels at inclusion (i.e. 1-2 years before progression) than non-progressors. ImmP had also lower CD4+T cell nadir and CD4+T cell count at inclusion, and VirP had higher HIV DNA levels in blood. T cell activation and IP10 levels at inclusion were significantly higher in ImmP than in non-progressors. In summary, the lasting loss of CD4+T cells, residual HIV replication and basal levels of immune activation appear to be major determinants of progression in HICs. These factors should be considered for adjusting their follow-up.

No MeSH data available.


Related in: MedlinePlus