The Early Bird Gets the Worm: Benefits and Future Directions With Early Antiretroviral Therapy Initiation in Primary Hiv Infection

Ramendra, Rayoun; Lu, Hongzhou; Routy, Jean Pierre

doi:10.2217/fvl-2018-0110

Cited by 15 publications

(13 citation statements)

References 45 publications

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“…These results suggest that plasma levels of CXCL13 progressively increases with HIV disease progression and is decreased without normalization upon initiation of ART. This is in line with previous findings that ART results in a decrease without normalization of systemic immune activation (40). Multivariate analysis confirmed that elevated CXCL13 levels among PLWH were independent of the effect of age, sex, HIV viral load, CD4 T cell count, and inflammatory markers.…”

Section: Resultssupporting

confidence: 93%

CXCL13 as a Biomarker of Immune Activation During Early and Chronic HIV Infection

et al. 2019

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Background: CXCL13 is preferentially secreted by Follicular Helper T cells (T FH ) to attract B cells to germinal centers. Plasma levels of CXCL13 have been reported to be elevated during chronic HIV-infection, however there is limited data on such elevation during early phases of infection and on the effect of ART. Moreover, the contribution of CXCL13 to disease progression and systemic immune activation have been partially defined. Herein, we assessed the relationship between plasma levels of CXCL13 and systemic immune activation. Methods: Study samples were collected in 114 people living with HIV (PLWH) who were in early (EHI) or chronic (CHI) HIV infection and 35 elite controllers (EC) compared to 17 uninfected controls (UC). A subgroup of 11 EHI who initiated ART and 14 who did not were followed prospectively. Plasma levels of CXCL13 were correlated with CD4 T cell count, CD4/CD8 ratio, plasma viral load (VL), markers of microbial translocation [LPS, sCD14, and (1→3)-β-D-Glucan], markers of B cell activation (total IgG, IgM, IgA, and IgG1-4), and inflammatory/activation markers like IL-6, IL-8, IL-1β, TNF-α, IDO-1 activity, and frequency of CD38 + HLA-DR + T cells on CD4 + and CD8 + T cells. Results: Plasma levels of CXCL13 were elevated in EHI (127.9 ± 64.9 pg/mL) and CHI (229.4 ± 28.5 pg/mL) compared to EC (71.3 ± 20.11 pg/mL), and UC (33.4 ± 14.9 pg/mL). Longitudinal analysis demonstrated that CXCL13 remains significantly elevated after 14 months without ART ( p < 0.001) and was reduced without normalization after 24 months on ART ( p = 0.002). Correlations were observed with VL, CD4 T cell count, CD4/CD8 ratio, LPS, sCD14, (1→3)-β-D-Glucan, total IgG, TNF-α, Kynurenine/Tryptophan ratio, and frequency of CD38+HLA-DR+ CD4 and CD8 T cells. In addition, CMV+ PLWH presented with higher levels of plasma CXCL13 than CMV- PLWH ( p = 0.005). Conclusion: Plasma CXCL13 levels increased with HIV disease progression. Early initiation of ART reduces plasma CXCL13 and B cell activation without normalization. CXCL13 represents a novel marker of systemic immune activation during early and chronic HIV infection and may be used to predict the development of non-AIDS events.

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Section: Resultssupporting

confidence: 93%

CXCL13 as a Biomarker of Immune Activation During Early and Chronic HIV Infection

et al. 2019

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“…Due to the success of ART, the life expectancy and quality of life of PLWH has dramatically improved over the course of the last decade. While early initiation of ART is associated with lower reservoir size and reduced immune activation, PLWH on ART still suffer from unrecovered epithelial gut damage and chronic immune activation ( 89 ). It has been recently reported that epithelial gut damage precedes systemic immune activation in a SIV-infected rhesus macaque model ( 7 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating LPS and (1→3)-β-D-Glucan: A Folie à Deux Contributing to HIV-Associated Immune Activation

et al. 2019

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Immune activation is the driving force behind the occurrence of AIDS and non-AIDS events, and is only partially reduced by antiretroviral therapy (ART). Soon after HIV infection, intestinal CD4+ T cells are depleted leading to epithelial gut damage and subsequent translocation of microbes and/or their products into systemic circulation. Bacteria and fungi are the two most abundant populations of the gut microbiome. Circulating lipopolysaccharide (LPS) and (1→3)-β-D-Glucan (βDG), major components of bacterial and fungal cell walls respectively, are measured as markers of microbial translocation in the context of compromised gut barriers. While LPS is a well-known inducer of innate immune activation, βDG is emerging as a significant source of monocyte and NK cell activation that contributes to immune dysfunction. Herein, we critically evaluated recent literature to untangle the respective roles of LPS and βDG in HIV-associated immune dysfunction. Furthermore, we appraised the relevance of LPS and βDG as biomarkers of disease progression and immune activation on ART. Understanding the consequences of elevated LPS and βDG on immune activation will provide insight into novel therapeutic strategies against the occurrence of AIDS and non-AIDS events.

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“…Poorer youth retention has been observed throughout the region: a large cohort analysis of ART patients in sub-Saharan Africa found youth (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) to have a higher risk of attrition than older adults [5]. ART care improves outcomes of people living with HIV and reduces transmission [6][7][8][9]. As youth on ART are a growing population [10], it is important to identify effective strategies to address youth-specific needs and prevent attrition from care.…”

Section: Introductionmentioning

confidence: 99%

Attrition from HIV care among youth initiating ART in youth‐only clinics compared with general primary healthcare clinics in Khayelitsha, South Africa: a matched propensity score analysis

et al. 2022

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Introduction: Youth living with HIV (YLWH) are less likely to initiate antiretroviral therapy (ART) and remain in care than older adults. It is important to identify effective strategies to address the needs of this growing population and prevent attrition from HIV care. Since 2008, two clinics have offered youth-targeted services exclusively to youth aged 12-25 in Khayelitsha, a high HIV-prevalence, low-income area in South Africa. We compared ART attrition among youth in these two clinics to youth in regular clinics in the same area. Methods: We conducted a propensity score matched cohort study of individuals aged 12-25 years initiating ART at eight primary care clinics in Khayelitsha between 1 January 2008 and 1 April 2018. We compared attrition, defined as death or loss to follow-up, between those attending two youth clinics and those attending general primary healthcare clinics, using Cox proportional hazards regression. Follow-up time began at ART initiation and ended at attrition, clinic transfer or dataset closure. We conducted sub-analyses of patients attending adherence clubs. Results: The distribution of age, sex and CD4 count at ART initiation was similar across Youth Clinic A (N = 1383), Youth Clinic B (N = 1299) and general clinics (N = 3056). Youth at youth clinics were more likely than those at general clinics to have initiated ART before August 2011 (Youth Clinic A: 16%, Youth Clinic B: 23% and general clinics: 11%). Youth clinics were protective against attrition: HR 0.81 (95% CI: 0.71-0.92) for Youth Clinic A and 0.85 (0.74-0.98) for Youth Clinic B, compared to general clinics. Youth Clinic A club patients had lower attrition after joining an adherence club than general clinic patients in adherence clubs (crude HR: 0.56, 95% CI: 0.32-0.96; adjusted HR: 0.48, 95% CI: 0.28-0.85), while Youth Clinic B showed no effect (crude HR: 0.83, 95% CI: 0.48-1.45; adjusted HR: 1.07, 95% CI: 0.60-1.90). Conclusions: YLWH were more likely to be retained in ART care in two different youth-targeted clinics compared to general clinics in the same area. Our findings suggest that multiple approaches to making clinics more youth-friendly can contribute to improving retention in this important group.

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The Early Bird Gets the Worm: Benefits and Future Directions With Early Antiretroviral Therapy Initiation in Primary Hiv Infection

Cited by 15 publications

References 45 publications

CXCL13 as a Biomarker of Immune Activation During Early and Chronic HIV Infection

CXCL13 as a Biomarker of Immune Activation During Early and Chronic HIV Infection

Circulating LPS and (1→3)-β-D-Glucan: A Folie à Deux Contributing to HIV-Associated Immune Activation

Attrition from HIV care among youth initiating ART in youth‐only clinics compared with general primary healthcare clinics in Khayelitsha, South Africa: a matched propensity score analysis

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