Dataset Information

Thymic Function as a Predictor of Immune Recovery in Chronically HIV-Infected Patients Initiating Antiretroviral Therapy.

ABSTRACT: Poor immunological responders (PIR) are HIV-infected patients with virologic suppression upon antiretroviral therapy (ART) but persistently low CD4⁺ T cell counts. Early identification of PIR is important given their higher morbimortality compared to adequate immune responders (AIR). In this study, 33 patients severely lymphopenic at ART onset, were followed for at least 36 months, and classified as PIR or AIR using cluster analysis grounded on their CD4⁺ T cell count trajectories. Based on a variety of immunological parameters, we built predictive models of PIR/AIR outcome using logistic regression. All PIR had CD4⁺ T cell counts consistently below 500 cells/?L, while all AIR reached this threshold. AIR showed a higher percentage of recent thymic emigrants among CD4⁺ T cells; higher numbers of sj-TRECs and greater sj/? TREC ratios; and significant increases in thymic volume from baseline to 12 months of ART. We identified mathematical models that correctly predicted PIR/AIR outcome after 36 months of therapy in 77-87% of the cases, based on observations made until 2-6 months after ART onset. This study highlights the importance of thymic activity in the immune recovery of severely lymphopenic patients, and may help to select the patients that will benefit from closer follow-up or novel therapeutic approaches.

SUBMITTER: Rb-Silva R

PROVIDER: S-EPMC6370619 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Thymic Function as a Predictor of Immune Recovery in Chronically HIV-Infected Patients Initiating Antiretroviral Therapy.

Rb-Silva Rita R Nobrega Claudia C Azevedo Cecilia C Athayde Emilia E Canto-Gomes João J Ferreira Ivo I Cheynier Rémi R Yates Andrew J AJ Horta Ana A Correia-Neves Margarida M

Frontiers in immunology 20190205

Poor immunological responders (PIR) are HIV-infected patients with virologic suppression upon antiretroviral therapy (ART) but persistently low CD4<sup>+</sup> T cell counts. Early identification of PIR is important given their higher morbimortality compared to adequate immune responders (AIR). In this study, 33 patients severely lymphopenic at ART onset, were followed for at least 36 months, and classified as PIR or AIR using cluster analysis grounded on their CD4<sup>+</sup> T cell count traje ...[more]

PMID: 30804925

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Project description:BackgroundThere is conflicting evidence on the immunologic benefit of treating helminth co-infections ("deworming") in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART.Methodology/principal findingsTo estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (? = 42.8; 95% CI, -2.1 to 87.7) or after the first year of ART (? = ?-9.9; 95% CI, -24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (? = 63.0; 95% CI, 6.0 to 120.1) in females.Conclusions/significanceEmpiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.

Project description:BACKGROUND:Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART). METHODS:In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound. RESULTS:Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-? (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 ?g/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-? levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness. CONCLUSIONS:Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-?), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.

Project description:AimTo evaluate the prevalence and associated factors of abnormal renal function among Ethiopian HIV-infected patients at baseline prior to initiation of antiretroviral therapy (ART) and during follow-up.MethodsWe conducted a retrospective observational cohort study of HIV infected patients who initiated ART at the outpatient ART clinic of Mehal Meda Hospital of North Shewa, Ethiopia from January 2012 to August 2018. Demographic and clinical data were abstracted from the medical records of patients. Renal function was assessed by estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation. Univariate and multivariate analysis were conducted to determine the factors associated with abnormal renal function at baseline and during follow-up.ResultsAmong 353 patients, 70 (19.8%) had baseline eGFR <60 ml/min/1.73m2 and 102 (28.9%) had eGFR = 60-89.9 ml/min/1.73m2. Factors associated with baseline renal impairment (eGFR <60 ml/min/1.73m2) included female sex (AOR = 3.52, CI 1.75-7.09), CD4 count < 200 cells/mm3 (AOR = 2.75, CI 1.40-5.42), BMI < 25 Kg/m2 (AOR = 3.04, CI 1.15-8.92), low hemoglobin (AOR = 2.19, CI 1.16-4.09) and high total cholesterol (AOR = 3.15, CI 1.68-5.92). After a median of 3.0 years of ART, the mean eGFR declined from 112.9 ± 81.2 ml/min/1.73m2 at baseline to 93.9 ± 60.6 ml/min/1.73m2 (P < 0.001). The prevalence of renal impairment increased from 19.8% at baseline to 22.1% during follow-up. Of 181 patients with baseline normal renal function, 49.7% experienced some degree of renal impairment. Older age (AOR = 3.85, 95% CI 2.03-7.31), female sex (AOR = 4.18, 95% CI 2.08-8.40), low baseline CD4 (AOR = 2.41, 95% CI 1.24-4.69), low current CD4 count (AOR = 2.32, 95% CI 1.15-4.68), high BMI (AOR = 2.91, 95% CI 1.49-5.71), and low hemoglobin (AOR = 3.38, 95% CI 2.00-7.46) were the factors associated with renal impairment during follow-up.ConclusionImpaired renal function was common in HIV-infected patients initiating ART in an outpatient setting in Ethiopia, and there appears to be a high prevalence of renal impairment after a median ART follow-up of 3 years. There is a need for assessment of renal function at baseline before ART initiation and regular monitoring of renal function for patients with HIV during follow-up.

Dataset Information

Thymic Function as a Predictor of Immune Recovery in Chronically HIV-Infected Patients Initiating Antiretroviral Therapy.

Publications

Thymic Function as a Predictor of Immune Recovery in Chronically HIV-Infected Patients Initiating Antiretroviral Therapy.

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