Dataset Information

One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study.

ABSTRACT: Immune activation in HIV-1-infected individuals is reduced under antiretroviral therapies, but persists, resulting in various morbidities. To better characterize this phenomenon, using a panel of 68 soluble and cell surface markers, we measured the level of activation in circulating CD4+ and CD8+ T cells, B cells, monocytes, NK cells, polynuclear and endothelial cells as well as of inflammation and fibrinolysis in 120 virologic responders over 45years of age. As compared with age- and sex-matched uninfected individuals, we observed a persistence of activation in all the cell subpopulations analyzed, together with marks of inflammation and fibrinolysis. Two independent hierarchical clustering analyses allowed us to identify five clusters of markers that varied concurrently, and five patient groups, each with the same activation profile. The five groups of patients could be characterized by a marker of CD4+ T cell, CD8+ T cell, NK cell, monocyte activation or of inflammation, respectively. One of these profiles was strongly associated with marks of metabolic syndrome, particularly with hyperinsulinemia (OR 12.17 [95% CI 1.79-82.86], p=0.011). In conclusion, our study unveils biomarkers linked to metabolic syndrome that could be tested as predictive markers, and opens the way to new therapeutic approaches tailored to each patient group.

SUBMITTER: Psomas C

PROVIDER: S-EPMC4919610 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study.

Psomas Christina C Younas Mehwish M Reynes Christelle C Cezar Renaud R Portalès Pierre P Tuaillon Edouard E Guigues Adeline A Merle Corinne C Atoui Nadine N Fernandez Céline C Le Moing Vincent V Barbuat Claudine C Marin Grégory G Nagot Nicolas N Sotto Albert A Eliaou Jean-François JF Sabatier Robert R Reynes Jacques J Corbeau Pierre P

EBioMedicine 20160510

Immune activation in HIV-1-infected individuals is reduced under antiretroviral therapies, but persists, resulting in various morbidities. To better characterize this phenomenon, using a panel of 68 soluble and cell surface markers, we measured the level of activation in circulating CD4+ and CD8+ T cells, B cells, monocytes, NK cells, polynuclear and endothelial cells as well as of inflammation and fibrinolysis in 120 virologic responders over 45years of age. As compared with age- and sex-matche ...[more]

PMID: 27428436

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Project description:ObjectivePrior hypothesis-driven studies identified immunophenotypic characteristics associated with the control of HIV replication without antiretroviral therapy (HIV controllers) as well as with the degree of CD4 T-cell recovery during ART. We hypothesized that an unbiased 'discovery-based' approach might identify novel immunologic characteristics of these phenotypes.DesignWe performed immunophenotyping on four 'aviremic' patient groups: HIV controllers (n = 98), antiretroviral-treated immunologic nonresponders (CD4 < 350; n = 59), antiretroviral-treated immunologic responders (CD4 > 350, n = 142), and as a control group HIV-negative adults (n = 43). We measured levels of T-cell maturation, activation, dysfunction, senescence, functionality, and proliferation.MethodsSupervised learning assessed the relative importance of immune parameters in predicting clinical phenotypes (controller, immunologic responder, or immunologic nonresponder). Unsupervised learning clustered immune parameters and examined if these clusters corresponded to clinical phenotypes.ResultsHIV controllers were characterized by high percentages of HIV-specific T-cell responses and decreased percentages of cells expressing human leukocytic antigen-antigen D related in naive, central memory, and effector T-cell subsets. Immunologic nonresponders were characterized by higher percentages of CD4 T cells that were TNFα+ or INFγ+, higher percentages of activated naive and central memory T cells, and higher percentages of cells expressing programmed cell death protein 1. Unsupervised learning found two distinct clusters of controllers and two distinct clusters of immunologic nonresponders, perhaps suggesting different mechanisms for the clinical outcomes.ConclusionOur discovery-based approach confirmed previously reported characteristics that distinguish aviremic individuals, but also identified novel immunologic phenotypes and distinct clinical subpopulations that should lead to more focused pathogenesis studies that might identify targets for novel therapeutic interventions.

Project description:BackgroundHIV low-level viremia (LLV) (51-999 copies/mL) can progress to treatment failure and increase potential for drug resistance. We analyzed retrospective longitudinal data from people living with HIV (PLHIV) on antiretroviral therapy (ART) in Kenya to understand LLV prevalence and virologic outcomes.MethodsWe calculated rates of virologic suppression (≤50 copies/mL), LLV (51-999 copies/mL), virologic non-suppression (≥1000 copies/mL), and virologic failure (≥2 consecutive virologic non-suppression results) among PLHIV aged 15 years and older who received at least 24 weeks of ART during 2015-2021. We analyzed risk for virologic non-suppression and virologic failure using time-dependent models (each viral load (VL) <1000 copies/mL used to predict the next VL).FindingsOf 793,902 patients with at least one VL, 18.5% had LLV (51-199 cp/mL 11.1%; 200-399 cp/mL 4.0%; and 400-999 cp/mL 3.4%) and 9.2% had virologic non-suppression at initial result. Among all VLs performed, 26.4% were LLV. Among patients with initial LLV, 13.3% and 2.4% progressed to virologic non-suppression and virologic failure, respectively. Compared to virologic suppression (≤50 copies/mL), LLV was associated with increased risk of virologic non-suppression (adjusted relative risk [aRR] 2.43) and virologic failure (aRR 3.86). Risk of virologic failure increased with LLV range (aRR 2.17 with 51-199 copies/mL, aRR 3.98 with 200-399 copies/mL and aRR 7.99 with 400-999 copies/mL). Compared to patients who never received dolutegravir (DTG), patients who initiated DTG had lower risk of virologic non-suppression (aRR 0.60) and virologic failure (aRR 0.51); similarly, patients who transitioned to DTG had lower risk of virologic non-suppression (aRR 0.58) and virologic failure (aRR 0.35) for the same LLV range.InterpretationApproximately a quarter of patients experienced LLV and had increased risk of virologic non-suppression and failure. Lowering the threshold to define virologic suppression from <1000 to <50 copies/mL to allow for earlier interventions along with universal uptake of DTG may improve individual and program outcomes and progress towards achieving HIV epidemic control.FundingNo specific funding was received for the analysis. HIV program support was provided by the President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Centers for Disease Control and Prevention (CDC).

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Dataset Information

One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study.

Publications

One of the immune activation profiles observed in HIV-1-infected adults with suppressed viremia is linked to metabolic syndrome: The ACTIVIH study.

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