Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection

Abstract

Background: Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours.

Methods: We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection. We measured the plasma levels of ten inflammatory markers.

Findings: After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis.

Interpretation: Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI.

Funding: ANRS and Paris-Saclay University.

Keywords: HIV infection; Immune activation; Inflammation; Long-term ART.

Fig. 1

Comparison of inflammatory profiles as shown by radar chart.

Fig. 2

Principal components analysis.

Fig. 3

Inflammatory levels measured at AHI diagnosis.

Fig. 4

Inflammatory levels and associations with non-HIV-related factors. (a) from multivariate linear (or logistic for CXCL10) regression models adjusted for sex. (b) from multivariate linear (or logistic for CXCL10) regression models adjusted for age. (c) from multivariate linear (or logistic for CXCL10) regression models adjusted for age and sex. Summary table of the associations between inflammatory levels and non-HIV related factors, obtained from multiple linear (or logistic for CXCL-10) regression models, by cohort. For each marker, the direction of the association is symbolized by a sign positive (+) or negative (-). P-values are estimated from likelihood-ratio test. Empty box is used to indicate a P-value > 0·15.