Microbial Translocation Is Linked to a Specific Immune Activation Profile in HIV-1-Infected Adults With Suppressed Viremia

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.

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Persistent Microbial Translocation and Immune Activation in HIV‐1–Infected South Africans Receiving Combination Antiretroviral Therapy

The Journal of Infectious Diseases ◽

10.1086/655229 ◽

2010 ◽

Vol 202 (5) ◽

pp. 723-733 ◽

Cited By ~ 136

Author(s):

Edana Cassol ◽

Susan Malfeld ◽

Phetole Mahasha ◽

Schalk van der Merwe ◽

Sharon Cassol ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Immune Activation ◽

Microbial Translocation ◽

Combination Antiretroviral Therapy ◽

South Africans ◽

Hiv 1

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Increase in frequencies of circulating Th-17 cells correlates with microbial translocation, immune activation and exhaustion in HIV-1 infected patients with poor CD4 T-cell reconstitution

Immunobiology ◽

10.1016/j.imbio.2016.01.002 ◽

2016 ◽

Vol 221 (5) ◽

pp. 670-678 ◽

Cited By ~ 12

Author(s):

Ranjini Valiathan ◽

Deshratn Asthana

Keyword(s):

T Cell ◽

Immune Activation ◽

Microbial Translocation ◽

Cd4 T Cell ◽

T Cell Reconstitution ◽

Th 17 ◽

Hiv 1

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Short Communication: Immune Activation Is Present in HIV-1-Exposed Seronegative Individuals and Is Independent of Microbial Translocation

AIDS Research and Human Retroviruses ◽

10.1089/aid.2015.0019 ◽

2016 ◽

Vol 32 (2) ◽

pp. 129-133 ◽

Cited By ~ 11

Author(s):

Irma Saulle ◽

Mara Biasin ◽

Federica Gnudi ◽

Veronica Rainone ◽

Salomè Valentina Ibba ◽

...

Keyword(s):

Immune Activation ◽

Short Communication ◽

Microbial Translocation ◽

Hiv 1

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Faculty Opinions recommendation of Persistent microbial translocation and immune activation in HIV-1-infected South Africans receiving combination antiretroviral therapy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.5770959.5753058 ◽

2010 ◽

Author(s):

Scott Sieg ◽

Nicholas Funderburg

Keyword(s):

Antiretroviral Therapy ◽

Immune Activation ◽

Microbial Translocation ◽

Combination Antiretroviral Therapy ◽

South Africans ◽

Hiv 1

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Alterations of the gut bacterial microbiota in rhesus macaques with SIV infection and on short- or long-term antiretroviral therapy

Scientific Reports ◽

10.1038/s41598-020-76145-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Summer Siddiqui ◽

Duran Bao ◽

Lara Doyle-Meyers ◽

Jason Dufour ◽

Yuntao Wu ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Gut Microbiota ◽

Immune Activation ◽

Rhesus Macaques ◽

Microbial Translocation ◽

Time Points ◽

Siv Infection ◽

The Impact ◽

Hiv 1

Abstract Gut dysbiosis and microbial translocation are associated with chronic systemic immune activation and inflammation in HIV-1 infection. However, the extent of restoration of gut microbiota in HIV-1 patients with short or long-term antiretroviral therapy (ART) is unclear. To understand the impact of ART on the gut microbiota, we used the rhesus macaque model of SIV infection to characterize and compare the gut microbial community upon SIV infection and during ART. We observed altered taxonomic compositions of gut microbiota communities upon SIV infection and at different time points of ART. SIV-infected animals showed decreased diversity of gut microbiome composition, while the ART group appeared to recover towards the diversity level of the healthy control. Animals undergoing ART for various lengths of time were observed to have differential gut bacterial abundance across different time points. In addition, increased blood lipopolysaccharide (LPS) levels during SIV infection were reduced to near normal upon ART, indicating that microbial translocation and immune activation can be improved during therapy. In conclusion, while short ART may be related to transient increase of certain pathogenic bacterial microbiome, ART may promote microbiome diversity compromised by SIV infection, improve the gut microbiota towards the healthy compositions and alleviate immune activation.

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Microbial Translocation and Immune Activation in HIV-1 Infected Pregnant Women

Current HIV Research ◽

10.2174/1570162x16666180731145011 ◽

2018 ◽

Vol 16 (3) ◽

pp. 208-215

Author(s):

Charles D. Mitchell ◽

Sady Dominguez ◽

Margaret Roach ◽

Varghese George ◽

Stefano Rinaldi ◽

...

Keyword(s):

Immune Activation ◽

Microbial Translocation ◽

Controlled Study ◽

Combined Effects ◽

Time Points ◽

Group A ◽

Hiv Women ◽

Prospective Longitudinal ◽

Hiv 1 ◽

Pregnancy Result

Background: Immune Activation (IA) has been previously documented in both pregnant (PG) and non-PG HIV-1 infected (HIV+) women as well as in HIV- uninfected PG women; the latter as a result of the fetal allograft. To determine whether the combined effects of HIV and pregnancy result in increased IA and whether IA is associated with Microbial Translocation (MT), we performed a prospective, longitudinal, controlled study during pregnancy and the postpartum (PP) period. Methods: HIV+ PG women had biomarkers of IA and MT tested at 12-20 weeks (T1), and 24-36 weeks (T2) of pregnancy and at 6-8 weeks Postpartum (T3). HIV+, non-PG women were tested at comparable time points. HIV- PG women were tested at T1 only. HIV+ women were not started on antiretroviral therapy (ART) until T1. Biomarkers of IA assessed included: CD4DR+, CD4CD38+, CD4DR+CD38+, CD8DR+, CD8CD38+, and CD8DR+CD38+. Biomarkers of MT included LPS, sCD14, and 16SrDNA. Results: 30 HIV+PG women, 18 HIV+ non-PG and 10 HIV-PG were enrolled. In the HIV+ women, there were no differences in median age, viral load, % or absolute CD4 at entry. Significant differences between T1 and T2 and between T1 and T3 were noted in CD8DR+CD38+ in HIV+PG women after ART. CD4DR+, CD4DR+CD38+, and CD8DR+ decreased post ART in HIV+PG women but a decline in IA was less evident in HIV+ non-PG. LPS decreased post ART by T3 in both HIV+PG and HIV+ non-PG groups; 16SrDNA was elevated at all time points in both groups when compared to control values, and declined post ART in the HIV+PG group. A subgroup of HIV-PG at T1 had IA and MT as evidenced by several IA markers and increased LPS. Conclusion: The degree of IA and MT was similar among HIV+PG and HIV+ non-PG women followed longitudinally. There was no incremental increase due to the combined effects of HIV and pregnancy. Several markers of IA and MT (LPS, 16SrDNA) decreased post ART. IA and MT occurred in a subgroup of HIV-PG women during the 1st trimester. Further study must be done to confirm whether MT consistently occurs in some healthy women during PG.

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