Immune Deficiency Could be An Early Risk Factor for Altered Insulin Sensitivity in Antiretroviral-Naive HIV-1-Infected Patients: The Anrs Copana Cohort

Abstract

Background

The relationships between immunovirological status, inflammatory markers, insulin resistance and fat distribution have not been studied in recently diagnosed (<1 year) antiretroviral-naive HIV-1-infected patients.

Methods

We studied 214 antiretroviral-naive patients at enrolment in the metabolic substudy of the ANRS COPANA cohort. We measured clinical, immunovirological and inflammatory parameters, glucose/insulin during oral glucose tolerance test (OGTT), adipokines, subcutaneous and visceral fat surfaces (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT], assessed by computed tomography) and the body fat distribution based on dual-energy X-ray absorptiometry (DEXA).

Results

Median age was 36 years; 28% of the patients were female and 35% of sub-Saharan origin; 20% had low CD4⁺ T-cell counts (≤200/mm³). Patients with low CD4⁺ T-cell counts were older and more frequently of sub-Saharan Africa origin, had lower body mass index (BMI) but no different SAT/VAT ratio and fat distribution than other patients. They also had lower total, low-density lipoprotein and high-density lipoprotein cholesterolaemia, higher triglyceridaemia and post-OGTT glycaemia, higher markers of insulin resistance (insulin during OGTT and homeostasis model assessment of insulin resistance) and of inflammation (high-sensitivity C-reactive protein, IL-6, tumour necrosis factor (TNF)-α, sTNFR1 and sTNFR2). After adjustment for age, sex, geographic origin, BMI and waist circumference, increased insulin resistance was not related to any inflammatory marker. In multivariate analysis, low CD4⁺ T-cell count was an independent risk factor for altered insulin sensitivity (β-coefficient for HOMA-IR: +0.90; P=0.001; CD4⁺ T-cell count >500/mm³ as the reference), in addition to older age (P: +0.26 for a 10-year increase; P=0.01) and higher BMI (P: +0.07 for a 1-kg/m² increase; P=0.003).

Conclusions

In ART-naive patients, severe immune deficiency but not inflammation could be an early risk factor for altered insulin sensitivity.

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