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.

Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

“…The residual inflammatory signature also depends on several factors, including the CD4 T cell count (both at the nadir and after treatment), the timing of ART, the patient's age and gender of the patients, and non-HIVrelated factors (overweight, viral co-infections, smoking, alcohol consumption, recreational drug abuse, drug toxicity, etc.) (106,113). Regardless of the exact nature of the inflammation that develops during a chronic ART-controlled HIV infection, the AT is highly sensitive to the inflammatory environment.…”

“…Importantly, patients with efficient immune restoration present inflammatory profile close to healthy individuals (106,113), suggesting a limited impact of currently used ARVs per se on inflammation. However, the question of the relative impact of HIV infection and ARV remains open when considering patients with partial immune restoration.…”

Pre-cART Immune Parameters in People Living With HIV Might Help Predict CD8+ T-Cell Characteristics, Inflammation Levels, and Reservoir Composition After Effective cART

“…Both IP-10, sCD14, and sCD163 were detected in all the samples tested. Moreover, IP-10 and sCD14 medians were considerably elevated compared to values corresponding to healthy donors found in the bibliography (Supplemental Figure 2C) [30][31][32][33][34][38][39][40][41].…”

“…Finally, plasma levels of IP-10, sCD14, and sCD163 were measured. These molecules have been proposed as markers of persistent inflammation in HIV infection since their levels remain elevated despite years of cART, compared to healthy donors [30][31][32][33][34][35][36][37]. Both IP-10, sCD14, and sCD163 were detected in all the samples tested.…”

Acute HIV-1 and SARS-CoV-2 Infections Share Slan+ Monocyte Depletion—Evidence from an Hyperacute HIV-1 Case Report

“…The establishment of the inflammatory state occurs early in HIV-1 infection, as shown by the increase in activation markers like HLA-DR highlighting their contribution to CD4+ T-cell activation [ 6 , 23 , 24 , 25 , 26 ]. The data on the monocyte phenotype during the acute HIV-1 infection are relatively scarce due to the rarity of these patients.…”