Residual Viremia Is Linked to a Specific Immune Activation Profile in HIV-1-Infected Adults Under Efficient Antiretroviral Therapy

Abstract

Chronic immune activation persists in persons living with HIV-1 even though they are aviremic under antiretroviral therapy, and fuels comorbidities. In previous studies, we have revealed that virologic responders present distinct profiles of immune activation, and that one of these profiles is related to microbial translocation. In the present work, we tested in 140 HIV-1-infected adults under efficient treatment for a mean duration of eight years whether low-level viremia might be another cause of immune activation. We observed that the frequency of viremia between 1 and 20 HIV-1 RNA copies/mL (39.5 ± 24.7% versus 21.1 ± 22.5%, p = 0.033) and transient viremia above 20 HIV-1 RNA copies/mL (15.1 ± 16.9% versus 3.3 ± 7.2%, p = 0.005) over the 2 last years was higher in patients with one profile of immune activation, Profile E, than in the other patients. Profile E, which is different from the profile related to microbial translocation with frequent CD38+ CD8+ T cells, is characterized by a high level of CD4+ T cell (cell surface expression of CD38), monocyte (plasma concentration of soluble CD14), and endothelium (plasma concentration of soluble Endothelial Protein C Receptor) activation, whereas the other profiles presented low CD4:CD8 ratio, elevated proportions of central memory CD8+ T cells or HLA-DR+ CD4+ T cells, respectively. Our data reinforce the hypothesis that various etiological factors shape the form of the immune activation in virologic responders, resulting in specific profiles. Given the type of immune activation of Profile E, a potential causal link between low-level viremia and atherosclerosis should be investigated.

Keywords: blip; coagulation; endothelium activation; inflammation; low-level viremia; virologic responder.

Figure 1

Correlations between low-level viremia, blips, and D-dimer plasma levels. Difference for each participant in the frequency where the participant displayed low-level viremia (A) or blips (B) over the two last years between participants with or without current detectable viremia. Difference in circulating D-dimer concentrations between participants with or without current detectable viremia. Statistical analyses were performed using a Mann-Whitney test (C). Correlation between the frequency of blips over the two last years and D-dimer plasma levels. Statistical analysis was performed using Kendall correlation (D).

Figure 2

Correlations between D-dimer level, participant age (A) and pretherapeutic CD4 count (B), CRP (C), sTNFRI (D), sCD163 (E), and sEPCR (F).

Figure 3

Differences in the frequency of current low-level viremia between the various IA profiles. Statistical analyses were performed using a Kruskal-Wallis H test (A). Differences in the frequency of low-level viremia (B) and blips (C) over the two last years between the various IA profiles. Statistical analyses were performed using a Mann-Whitney test.

Figure 4

Differences in CD4 count (A), CD4:CD8 ratio (B), sCD14 (C), frequency of CD4+ T cells expressing CD38 (D), and sEPCR (E) between healthy donors (HD) and people living with HIV-1 with the five IA profiles. Statistical analyses were performed using a Mann-Whitney test. Correlation between low-level viremia over the two last years and tPA in Profile E participants. Statistical analysis was performed using Spearman correlation (F).