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. 2023 Jun 1;37(7):1035-1046.
doi: 10.1097/QAD.0000000000003546. Epub 2023 Mar 14.

Mechanisms of systemic low-grade inflammation in HIV patients on long-term suppressive antiretroviral therapy: the inflammasome hypothesis

Florent Guerville  1 , Marine Vialemaringe  2 , Celine Cognet  3 , Pierre Duffau  1   4 , Estibaliz Lazaro  1   5 , Charles Cazanave  6 , Fabrice Bonnet  2   7 , Olivier Leleux  2 , Rodrigue Rossignol  8 , Benoît Pinson  9 , Camille Tumiotto  10 , Frederic Gabriel  11 , Victor Appay  1 , Julie Déchanet-Merville  1 , Linda Wittkop  2   12   13 , Benjamin Faustin  1   14 , Isabelle Pellegrin  1   3 ; on the behalf of ANRS CO3 Aquitaine / AquiVIH-NA study group
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Mechanisms of systemic low-grade inflammation in HIV patients on long-term suppressive antiretroviral therapy: the inflammasome hypothesis

Florent Guerville et al. AIDS. .

Abstract

Objective: We aimed to determine the contribution of inflammasome activation in chronic low-grade systemic inflammation observed in patients with HIV (PWH) on long-term suppressive antiretroviral therapy (ART) and to explore mechanisms of such activation.

Design: Forty-two PWH on long-term suppressive ART (HIV-RNA < 40 copies/ml) were compared with 10 HIV-negative healthy controls (HC).

Methods: Inflammasome activation was measured by dosing mature interleukin (IL)-1β and IL-18 cytokines in patient serum. We explored inflammasome pathways through ex vivo stimulation of PWH primary monocytes with inflammasome activators; expression of inflammasome components by transcriptomic analysis; and metabolomics analysis of patient sera.

Results: Median (Q1; Q3) age, ART and viral suppression duration in PWH were 54 (48; 60), 15 (9; 20) and 7.5 (5; 12) years, respectively. Higher serum IL-18 was measured in PWH than in HC (61 (42; 77) vs. 36 (27-48 pg/ml), P = 0.009); IL-1β was detected in 10/42 PWH (0.5 (0.34; 0.80) pg/ml) but not in HC. Monocytes from PWH did not produce more inflammatory cytokines in vitro , but secretion of IL-1β in response to NOD like receptor family, pyrin domain containing 3 (NLRP3) inflammasome stimulation was higher than in HC. This was not explained at the transcriptional level. We found an oxidative stress molecular profile in PWH sera.

Conclusion: HIV infection with long-term effective ART is associated with a serum inflammatory signature, including markers of inflammasome activation, and an increased activation of monocytes upon inflammasome stimulation. Other cells should be investigated as sources of inflammatory cytokines in PWH. Oxidative stress might contribute to this chronic low-grade inflammation.

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References

    1. Deeks SG, Phillips AN. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity . BMJ 2009; 338:a3172.
    1. Kiplagat J, Tran DN, Barber T, Njuguna B, Vedanthan R, Triant VA, et al. How health systems can adapt to a population ageing with HIV and comorbid disease . Lancet HIV 2022; 9:e281–e292.
    1. de Coninck Z, Hussain-Alkhateeb L, Bratt G, Ekström AM, Gisslén M, Petzold M, et al. Non-AIDS mortality is higher among successfully treated people living with HIV compared with matched HIV-negative control persons: a 15-year follow-up cohort study in Sweden . AIDS Patient Care STDs 2018; 32:297–305.
    1. Croxford S, Kitching A, Desai S, Kall M, Edelstein M, Skingsley A, et al. Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort . Lancet Public Health 2017; 2:e35–e46.
    1. Wada N, Jacobson LP, Cohen M, French A, Phair J, Muñoz A. Cause-specific life expectancies after 35 years of age for human immunodeficiency syndrome-infected and human immunodeficiency syndrome-negative individuals followed simultaneously in long-term cohort studies, 1984–2008 . Am J Epidemiol 2013; 177:116–125.

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