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.

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.
Competing Interests: Declaration of Competing Interest Dr. Avettand-Fenoël reports grants from ANRS, during the conduct of the study; grants and personal fees from ViiV, grants from Janssen, outside the submitted work. Dr. Reynes reports personal fees and non-financial support from Gilead Science, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from MSD France, personal fees and non-financial support from Janssen, personal fees and non-financial support from Pfizer, outside the submitted work. Dr. Molina reports personal fees from Gilead Sciences, personal fees from Merck, personal fees from ViiV Healthcare, outside the submitted work. Dr. Launay reports grants from Assistance Publique - Hopitaux de Paris (AP-HP), during the conduct of the study. Dr. Novelli, Dr. Lécuroux, Dr. Villemant, Dr. Essat, Dr. Blum , Dr. Bourgeois, Dr. Goujard and Dr. Meyer have nothing to disclose.
(Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)