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.

High residual inflammation despite HIV viral suppression: Lessons learned from real‐time adherence monitoring among people with HIV in Africa

“…Whiskers represent the lowest and highest observations within the region defined by the limits Q1 -1.5 × IQR and Q3 + 1.5 × IQR. IL-6, interleukin 6; sCD14, soluble CD14 explanation could be derived from previous observations where incomplete ART adherence has been associated with residual viral replication [32,33], and where residual viral replication has been linked to heightened systemic inflammation [34][35][36]; however, other studies have not confirmed these findings [37,38]. Another possible driver of this association is that PWH who are not fully adherent to ART are more likely to accumulate risk factors and/or comorbidities that are also associated with high inflammation, immune activation and/or coagulopathy such as diabetes mellitus or chronic infections.…”

Markers of ovarian reserve in women living with HIV: A systematic review

“…Detectable viral load and low CD4 count emerged in the two largest studies as having a deleterious effect on AMH, raising a question as to whether immune activation may act as a mechanism to decrease ovarian reserve [16,19]. As both HIV viremia and low CD4 tend to be accompanied by states of immune activation [32,33], these findings present the possibility of inflammation playing a pivotal role in ovarian aging. Recent evidence has linked decreased ovarian reserve and pathologic imbalances of proinflammatory and anti‐inflammatory cytokines [34].…”

Two-Drug Regimens for HIV—Current Evidence, Research Gaps and Future Challenges

“…In addition, low level viremia (LLV) has emerged as another biomarker of HIV persistent replication although its definition varies across studies due to differences in RNA-HIV quantification methods. Previous studies have reported an association between LLV, defined as an HIV-RNA VL between 1 and 20 copies/mL, higher levels of pro-inflammatory biomarkers (i.e., d-dimer, soluble CD163, soluble endothelial protein C receptor) [55,56], a larger HIV latent reservoir size [57] and a higher risk for non-AIDS events or death [58]. Moreover, contradictory results have been reported regarding whether LLV may be different between PI-based and DTG-based 3DRs [57,[59][60][61].…”