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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

Study flow diagram.ANRS: Agence Nationale de Recherche sur le SIDA et les Hépatites Virales, cART: antiretroviral therapy, CODEX: Cohorte des Extrêmes study, HICs: HIV controllers.
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pone.0131922.g001: Study flow diagram.ANRS: Agence Nationale de Recherche sur le SIDA et les Hépatites Virales, cART: antiretroviral therapy, CODEX: Cohorte des Extrêmes study, HICs: HIV controllers.

Mentions: We recorded all suspected progressions among the CODEX HICs until June 30th, 2013. As shown in Fig 1, 37 out of the 217 HICs experienced at least one suspected progression. Twenty-six patients experienced at least one or two drops in their CD4+ T cell count (this situation occurred twice in two patients, leading to 28 suspected immunologic progressions). Six patients had at least one HIV RNA VL above 2000 copies/mL, and 5 patients had both criteria at the same time for a single blood sample.


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)

Study flow diagram.ANRS: Agence Nationale de Recherche sur le SIDA et les Hépatites Virales, cART: antiretroviral therapy, CODEX: Cohorte des Extrêmes study, HICs: HIV controllers.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131922.g001: Study flow diagram.ANRS: Agence Nationale de Recherche sur le SIDA et les Hépatites Virales, cART: antiretroviral therapy, CODEX: Cohorte des Extrêmes study, HICs: HIV controllers.
Mentions: We recorded all suspected progressions among the CODEX HICs until June 30th, 2013. As shown in Fig 1, 37 out of the 217 HICs experienced at least one suspected progression. Twenty-six patients experienced at least one or two drops in their CD4+ T cell count (this situation occurred twice in two patients, leading to 28 suspected immunologic progressions). Six patients had at least one HIV RNA VL above 2000 copies/mL, and 5 patients had both criteria at the same time for a single blood sample.

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