Effects of Early and Delayed Antiretroviral Therapy on Plasma Anti-CD4 Autoreactive IgG and Its Association With CD4+ T-Cell Recovery in Acute HIV-Infected Individuals

Song, Aixin; Li, Zhen; Luo, Zhenwu; Lu, Xiaofan; Wang, Rui; Liu, Lifeng; Xia, Wei; Wan, Zhuang; Zhang, Tong; Su, Bin; Jiang, Wei; Wu, Hao

doi:10.3389/fphar.2020.00449

Cited by 11 publications

(9 citation statements)

References 47 publications

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“…We also observed a similar result that the negative association trends between the frequency of IL-21 + ICOS + cTfh cells and CD4 + T cell count in both acute and chronic HIV-1 infection stage ( Figure 5A ). Our previous study demonstrated that higher level of anti-CD4 antibody is responsible for CD4 + T cell depletion during HIV-1 acute infection ( 70 ). Therefore, we hypothesize that the overactivation of cTfh cells with high ICOS level and more IL-21 secretion by ICOS + cTfh cells induces the excessive anti-CD4 antibody generation, thereby promoting the progression of CD4 + T cell loss even the induction of idiopathic CD4 lymphopenia ( 71 ).…”

Section: Discussionmentioning

confidence: 99%

Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection

Zhang

Cheung

et al. 2022

Front. Immunol.

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Interactions between T follicular helper (Tfh) cells and germinal center B cells are essential for the differentiation of B cells and specific antibody responses against HIV-1 infection. However, the extent to which HIV-1 infection affects the dynamic interplay between these two cell populations in the bloodstream remains unclear. In this study, the dynamics of circulating Tfh (cTfh) and B cells and their relationship in individuals with acute and chronic HIV-1 infection were investigated. Twenty-five study subjects were enrolled from the Beijing PRIMO clinical cohort, a prospective cohort of HIV-1-negative men who have sex with men (MSM) for the identification of cases of acute HIV-1 infection (AHI) at Beijing Youan Hospital, Capital Medical University. Individuals with AHI were selected at random. Matched samples were also collected and analyzed from the same patients with chronic HIV-1 infection. None of the study subjects received antiretroviral therapy during acute or chronic infection. Multicolor flow cytometry was used for the immunophenotypic and functional characterization of cTfh cell and B cell subsets. AHI resulted in increased proportions in bulk cTfh, ICOS+cTfh or IL-21+ICOS+cTfh cells. In both acute and chronic infections, activated memory (AM), tissue-like memory (TLM), and plasmablast (PB) B cell levels were increased whilst resting memory (RM) and naïve mature (NM) B cell levels were decreased. Classical memory (CM) B cells were unaffected during infection. Association analyses showed that the levels of ICOS+cTfh and IL-21+ICOS+cTfh cells were negatively correlated with those of AM, CM, RM cells, and positively correlated with those of NM cells in AHI but not chronic HIV-1 infection stage (CHI). Moreover, the frequency of IL-21+ICOS+cTfh cells was also positively correlated with plasma HIV-1 viral load, and had an opposite association trend with CD4+T cell count in AHI. Our data suggests that HIV-1 infection drives the expansion of cTfh cells, which in turn leads to perturbations of B cell differentiation through ICOS signaling during acute infection stage. These findings provide insight on the role of ICOS in the regulation of cTfh/B cell interaction during AHI and may potentially guide the design of effective strategies for restoring anti-HIV-1 immunity in the infected patients.

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Section: Discussionmentioning

confidence: 99%

Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection

Zhang

Cheung

et al. 2022

Front. Immunol.

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“…Recovery of CD4 lymphocytes occurs in the first 2 years after starting ART and is associated with age and the pre-existing degree of HIV-1-related immunodeficiency, so long-term exposure to HIV-1 infection damages the immune system in ways that are difficult to correct due to exhaustion 32 – 34 .…”

Section: Discussionmentioning

confidence: 99%

Predictors of attrition among adults in a rural HIV clinic in southern Mozambique: 18-year retrospective study

Nacarapa¹,

Verdu²,

Nacarapa³

et al. 2021

Sci Rep

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HIV remains a major cause of morbidity and mortality for people living in many low-income countries. With an HIV prevalence of 12.4% among people aged over 15 years, Mozambique was ranked in 2019 as one of eight countries with the highest HIV rates in the world. We analyzed routinely collected data from electronical medical records in HIV-infected patients aged 15 years or older and enrolled at Carmelo Hospital of Chokwe in Chokwe from 2002 to 2019. Attrition was defined as individuals who were either reported dead or lost to follow-up (LTFU) (≥ 90 days since the last clinic visit with missed medical pick-up after 3 days of failed calls). Kaplan–Meier survival curves and Cox regression analyses were used to model the incidence and predictors of time to attrition. From January 2002 to December 2019, 16,321 patients were enrolled on antiretroviral therapy (ART): 59.2% were women, and 37.9% were aged 25–34 years old. At the time of the analysis, 7279 (44.6%) were active and on ART. Overall, the 16,321 adults on ART contributed a total of 72,987 person-years of observation. The overall attrition rate was 9.46 per 100 person-years. Cox regression showed a higher risk of attrition in those following an inpatient regimen (hazard ratio [HR] 3.18, 95% confidence interval [CI] 2.89–3.50; p < 0.001), having CD4 counts under 50 cells/µL (HR 1.91, 95% CI 1.63–2.24, p < 0.001), receiving anti-TB treatment within 90 days of ART initiation (HR 6.53, 95% CI 5.72–7.45; p < 0.001), classified as WHO clinical stage III (HR 3.75, 95% CI 3.21–4.37; p < 0.001), and having Kaposi’s sarcoma (HR 1.99, 95% CI 1.65–2.39, p < 0.001). Kaplan–Meier analysis showed that patients with CD4 counts of less than 50 cells/µL on ART initiation had a 40% lower chance of survival at 18 years. Low CD4 cell counts, ART initiation as an inpatient, WHO clinical stage III, and anti-tuberculosis treatment within 90 days of ART initiation were strongly associated with attrition. Strengthening HIV testing and ART treatment, improving the diagnosis of tuberculosis before ART initiation, and guaranteed psychosocial support systems are the best tools to reduce patient attrition after starting ART.

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“…Other observation and randomized cohort studies also showed that baseline HIV viral load > 500 000 copies/mL is associated with virological failure, leading to immune failure [40–44]. From the perspective of clinical relevance, these results also highlighted the benefits of the policy of ‘early detection and early treatment’ in the immune restoration [45]. Further studies are needed to verify the potential mechanism underlying this phenomenon.…”

Section: Discussionmentioning

confidence: 83%

Demographic and clinical factors associated with immune reconstitution in HIV/HBV co‐infected and HIV mono‐infected patients: a retrospective cohort study

Jiang

Hou

et al. 2020

HIV Medicine

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Objectives To describe the clinical characteristics and factors associated with CD4 T‐cell count and CD4/CD8 ratio restoration in HIV mono‐infected and HIV/HBV co‐infected individuals, and to explore liver and renal functional changes in both groups. Methods A retrospective cohort study was performed including 356 HIV/HBV co‐infected and 716 HIV mono‐infected participants who initiated antiretroviral therapy (ART) during 2013–2017 in Beijing Youan Hospital, China. Demographic and clinical characteristics were compared between the two groups, using χ2 and Mann–Whitney non‐parametric tests. Bivariate and multivariate Cox regression models were used to test their association. Results Baseline HIV viral load and ART regimen were found to be significantly associated with CD4 T‐cell restoration among HIV‐infected participants, whereas baseline HIV viral load was the only significant factor associated with CD4 T‐cell restoration in HIV/HBV co‐infected participants. The final model showed that baseline HIV viral load and ART regimen were significantly associated with CD4/CD8 ratio restoration among HIV‐infected participants, while baseline HIV viral load was the significant factor. Liver and renal functions were similar at the endpoint (P > 0.05). Conclusions Baseline HIV viral load count was found to be the key factor affecting immune restoration in both HIV and HIV/HBV individuals. Future multi‐wave prospective studies are needed to clarify the potential biological mechanism.

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Effects of Early and Delayed Antiretroviral Therapy on Plasma Anti-CD4 Autoreactive IgG and Its Association With CD4+ T-Cell Recovery in Acute HIV-Infected Individuals

Cited by 11 publications

References 47 publications

Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection

Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection

Predictors of attrition among adults in a rural HIV clinic in southern Mozambique: 18-year retrospective study

Demographic and clinical factors associated with immune reconstitution in HIV/HBV co‐infected and HIV mono‐infected patients: a retrospective cohort study

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