Abnormal Levels of Some Biomarkers of Immune Activation Despite Very Early Treatment of Human Immunodeficiency Virus

Schnittman, Samuel R; Deitchman, Amelia N.; Beck-Engeser, Gabriele; Ahn, Haelee; York, Vanessa A.; Hartig, Heather; Hecht, Frederick; Martin, Jeffrey N.; Deeks, Steven G.; Aweeka, Francesca; Hunt, Peter W.

doi:10.1093/infdis/jiaa580

Cited by 25 publications

(49 citation statements)

References 59 publications

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“…In neither of the infected groups with viral suppression was the reduction in inflammation ‘complete’, and concentrations of several of the CSF biomarkers were higher than in the HIV-uninfected controls. This was also the case with several of the systemic inflammatory biomarkers that did not fully normalize in these two settings as has also been documented in other studies [ 40 , 52 , 53 , 65 , 94 ]. Residual CSF biomarker elevations in the ART- suppressed groups included TNFα, CXCL10, sCD14, sCD163 and sVCAM-1, while several others showed elevations that did not reach statistical significance.…”

Section: Resultssupporting

confidence: 85%

“…Like systemic HIV-1 infection [ 52 , 53 ], CNS infection is accompanied by local inflammation that is reduced in the face of effective ART [ 6 ]. For example, levels of CSF neopterin, an extensively studied inflammatory biomarker in HIV infection [ 8 ], fall very rapidly after ART initiation [ 54 ], and CSF pleocytosis characteristically also resolves, though generally more slowly [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression

et al. 2021

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Objective To characterize the evolution of central nervous system (CNS) inflammation in HIV-1 infection applying a panel of cerebrospinal fluid (CSF) inflammatory biomarkers to grouped subjects representing a broad spectrum of systemic HIV-1 immune suppression, CNS injury and viral control. Methods This is a cross-sectional analysis of archived CSF and blood samples, assessing concentrations of 10 functionally diverse soluble inflammatory biomarkers by immunoassays in 143 HIV-1-infected subjects divided into 8 groups: untreated primary HIV-1 infection (PHI); four untreated groups defined by their blood CD4+ T lymphocyte counts; untreated patients presenting with subacute HIV-associated dementia (HAD); antiretroviral-treated subjects with ≥1 years of plasma viral suppression; and untreated elite controllers. Twenty HIV-1-uninfected controls were included for comparison. Background biomarkers included blood CD4+ and CD8+ T lymphocytes, CSF and blood HIV-1 RNA, CSF white blood cell (WBC) count, CSF/blood albumin ratio, CSF neurofilament light chain (NfL), and CSF t-tau. Findings HIV-1 infection was associated with a broad compartmentalized CSF inflammatory response that developed early in its course and changed with systemic disease progression, development of neurological injury, and viral suppression. CSF inflammation in untreated individuals without overt HAD exhibited at least two overall patterns of inflammation as blood CD4+ T lymphocytes decreased: one that peaked at 200–350 blood CD4+ T cells/μL and associated with lymphocytic CSF inflammation and HIV-1 RNA concentrations; and a second that steadily increased through the full range of CD4+ T cell decline and associated with macrophage responses and increasing CNS injury. Subacute HAD was distinguished by a third inflammatory profile with increased blood-brain barrier permeability and robust combined lymphocytic and macrophage CSF inflammation. Suppression of CSF and blood HIV-1 infections by antiretroviral treatment and elite viral control were associated with reduced CSF inflammation, though not fully to levels found in HIV-1 seronegative controls.

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Section: Resultssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression

et al. 2021

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“…Collectively, these observations support the notion of relative immunosuppression during pregnancy, which partially reverses in the third trimester [ 30 ]. The magnitude of these relative changes in immune activation among PWWH compared with those seen in pregnant women without HIV is currently unknown, particularly given that microbial translocation—which is significantly greater in treated HIV compared with the HIV-negative population—may be a key effect modifier in the relationship between immune activation and stage of pregnancy [ 41 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Changes in Immune Activation During Pregnancy and the Postpartum Period in Treated HIV Infection

Schnittman

Byakwaga

Boum

et al. 2021

Open Forum Infectious Diseases

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Background Pregnant women with HIV (PWWH) have high postpartum morbidity and mortality from infections like tuberculosis. Immunologic changes during pregnancy and postpartum periods may contribute to these risks, particularly the immunoregulatory kynurenine pathway of tryptophan catabolism, which contributes to both HIV and tuberculosis pathogenesis and increases in the early postpartum. Methods Women with HIV initiating ART in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort who were pregnant at enrollment or became pregnant during observation were studied (N=54). Plasma kynurenine/tryptophan (KT) ratio, sCD14, sCD163, sCD27, IP-10, D-dimer, IL-6, and I-FABP levels were assessed through the first year of ART and at 3-month intervals throughout pregnancy and one year postpartum. Biomarker changes were assessed with linear mixed models adjusted for ART duration. Hemoglobin concentration changes were used to estimate pregnancy-related changes in plasma volume. Results Median baseline CD4 was 134. D-dimer increased through the third trimester before returning to baseline postpartum while most other biomarkers declined significantly during pregnancy, beyond what would be expected from pregnancy-associated plasma volume expansion. IP-10 and sCD14 remained suppressed for at least 12 months postpartum. KT ratio was the only biomarker that increased above pre-pregnancy baseline in the postpartum (mean +30%, P<0.001) and remained higher than baseline for >9 months (P<0.045 for all timepoints). Conclusions Several immune activation markers decline during pregnancy and remain suppressed postpartum, but the kynurenine pathway of tryptophan catabolism increases above baseline for >9 months postpartum. The mechanisms underlying postpartum kynurenine pathway activity are incompletely understood, but may contribute to increased tuberculosis risk in this setting.

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“…Immune activation has been demonstrated to persist in HIV chronic infection with alteration in kynurenine-tryptophan ratio, a marker of defective adaptive immunity, even in patients treated early for HIV infection. 33 , 34…”

Section: Discussionmentioning

confidence: 99%

“…32 Immune activation has been demonstrated to persist in HIV chronic infection with alteration in kynureninetryptophan ratio, a marker of defective adaptive immunity, even in patients treated early for HIV infection. 33,34 On the other hand, HIV and SARS-CoV-2 share a common evasion of innate immunity, 35 that could explain a deficient response to Interferon.…”

Section: Discussionmentioning

confidence: 99%

HIV and SARS-CoV-2 Co-Infection: What are the Risks?

Squillace¹,

Ricci²,

Colella³

et al. 2021

IDR

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The dramatic increase of the global pandemic of SARS-CoV-2 infection represents a critical issue that needs to be investigated to evaluate the associated risk factors for acquisition and worse outcome. The interplay between immune activation and immune depression during SARS-CoV-2 infection is an intriguing topic that still needs to be clarified. The role of HIV in SARS-CoV-2 infection is not well defined. Chronic inflammation linked to HIV infection could be a driver for a worse prognosis in people living with HIV (PLWH). We explored the role of HIV as a risk factor for SARS-CoV-2 infection and severity and which factors contributed to a worse prognosis when HIV infection was present. PubMed/MEDLINE was searched for “COVID-19” or “SARS-CoV2” and “HIV” or “AIDS” and (“hospitalization” or “intensive care” or “mechanical ventilation” or “death” OR “mortality”), both in MeSH and as free text in all fields. Our review focused on 21 studies that enrolled at least 40 PLWH. In most studies, HIV infection did not represent a risk factor for SARS-CoV-2 infection. On the contrary, the risk of severe COVID-19 and hospitalization was higher in PLWH. Low CD4 cell count consistently emerged as a risk factor for severe COVID-19. Comorbidities, either in people with or without HIV diagnosis, played a key role, especially because of their early development in PLWH.

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Abnormal Levels of Some Biomarkers of Immune Activation Despite Very Early Treatment of Human Immunodeficiency Virus

Cited by 25 publications

References 59 publications

Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression

Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression

Changes in Immune Activation During Pregnancy and the Postpartum Period in Treated HIV Infection

HIV and SARS-CoV-2 Co-Infection: What are the Risks?

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