Late Antiretroviral Therapy (ART) Initiation Is Associated with Long-Term Persistence of Systemic Inflammation and Metabolic Abnormalities

Objectives

HIV-induced immunodeficiency is associated with metabolic abnormalities and systemic inflammation. We investigated the effect of antiretroviral therapy (ART) on restoration of insulin sensitivity, markers of immune activation and inflammation.

Methods

Immunological, metabolic and inflammatory status was assessed at antiretroviral therapy initiation and three years later in 208 patients from the ANRS-COPANA cohort. Patients were compared according to their pre-ART CD4⁺ cell count (group 1: ≤ 200/mm³, n = 66 vs. group 2: > 200/mm³, n = 142).

Results

Median CD4⁺ cell count increased in both groups after 3 years of successful ART but remained significantly lower in group 1 than in group 2 (404 vs 572 cells/mm³). Triglyceride and insulin levels were higher or tended to be higher in group 1 than in group 2 at ART initiation (median: 1.32 vs 0.97 mmol/l, p = 0.04 and 7.6 vs 6.8 IU, p = 0.09, respectively) and remained higher after three years of ART (1.42 vs 1.16 mmol/L, p = 0.0009 and 8.9 vs 7.2 IU, p = 0.01). After adjustment for individual characteristics and antiretroviral therapy regimens (protease inhibitor (PI), zidovudine), insulin levels remained significantly higher in patients with low baseline CD4⁺cell count. Baseline IL-6, sCD14 and sTNFR2 levels were higher in group 1 than in group 2. Most biomarkers of immune activation/inflammation declined during ART, but IL-6 and hsCRP levels remained higher in patients with low baseline CD4⁺ cell count than in the other patients (median are respectively 1.4 vs 1.1 pg/ml, p = 0.03 and 2.1 vs 1.3 mg/ml, p = 0.07).

Conclusion

After three years of successful ART, low pretreatment CD4⁺ T cell count remained associated with elevated insulin, triglyceride, IL-6 and hsCRP levels. These persistent metabolic and inflammatory abnormalities could contribute to an increased risk of cardiovascular and metabolic disease.

Below:  Distribution of inflammatory markers according to CD4 T cell count at ART initiation

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By:  

Mathilde Ghislain, Laurence Meyer, Cécile Goujard

Inserm UMRS1018, CESP, Epidemiology of HIV and STI, Le Kremlin-Bicêtre, France

Jean-Philippe Bastard, Jacqueline Capeau, Soraya Fellahi

Tenon Hospital, AP-HP, Department of Biochemistry and Hormonology, Paris, France

Jean-Philippe Bastard, Jacqueline Capeau, Soraya Fellahi, Corinne Vigouroux

Inserm UMRS 938, Centre de Recherche Saint-Antoine, Paris, France

Jean-Philippe Bastard, Jacqueline Capeau, Soraya Fellahi, Corinne Vigouroux

Sorbonne Universities, UPMC, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France

Laurence Meyer, Cécile Goujard

Paris-Sud university, Le Kremlin-Bicêtre, France

Laurence Meyer

Bicêtre Hospital, AP-HP, Department of Public Health, Le Kremlin-Bicêtre, France

Laurence Gérard

Saint-Louis Hospital, AP-HP, Department of Clinic Immunopathology, Paris, France

Thierry May

Teaching hospital of Nancy, Brabois Hospitals, Department of Infectious and Tropical Diseases, Vandoeuvre les Nancy, France

Anne Simon

Pitié-Salpétrière Hospital, AP-HP, Department of Internal Medicine and Clinical Immunology, Paris, France

Corinne Vigouroux

Saint-Antoine Hospital, AP-HP, Common Laboratory of Biology and Molecular Genetics, Paris, France

Cécile Goujard

Bicêtre Hospital, AP-HP, Department of Internal Medicine, Le Kremlin-Bicêtre, France

ANRS-COPANA Cohort Study Group

Inserm-ANRS, Paris, France

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