Evaluating the use of procalcitonin in an asymptomatic, HIV-infected antiretroviral therapy-naïve, South African cohort

2016 ◽  
Vol 54 (3) ◽  
Author(s):  
Dineo V. Phatlhane ◽  
Hayley Ipp ◽  
Rajiv T. Erasmus ◽  
Annalise E. Zemlin
Keyword(s):  
T Cells ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Immune Activation ◽  
Serum Samples ◽  
Cross Sectional ◽  
Cd4 Counts ◽  
Persistent Inflammation ◽  
Significant Difference

AbstractThe chronic stage of human immunodeficiency virus (HIV) infection, although clinically asymptomatic, is characterized by activation of the immune system and persistent inflammation. Procalcitonin (PCT) has been studied in HIV infection as a marker of bacterial infection. Our aim was to assess the effect of persistent immune activation on PCT levels in asymptomatic treatment naïve HIV infected subjects.This was a cross-sectional study of 68 asymptomatic antiretroviral therapy-naive HIV infected participants and 42 uninfected controls. Stored serum samples were used to measure: PCT, interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP), high sensitivity C-reactive protein (hsCRP), immunoglobulin G (IgG) and albumin. PCT was correlated with markers of: disease progression (CD4 count and viral load), immune activation (CD 38 on CD8+ T cells, IgG and LBP), inflammation (IL-6, hsCRP and albumin).IL-6, IgG and CD8/38 were all significantly increased while albumin and CD4 counts were significantly lower in the HIV infected group. PCT levels were not significantly different between the two groups. There was no significant difference in LBP and hsCRP; however, their levels were increased in both groups. PCT correlated only with LBP (p=0.0001). IL-6 and LBP correlated positively with hsCRP and IgG. Albumin correlated inversely with IL-6 and viral load. Only IgG and CD8/38 correlated inversely with CD4 counts.We demonstrated the activation of the innate (raised LBP), humoral (raised IgG) and cellular immune systems (increased CD8/38 T cells). Despite a state of persistent inflammation, PCT levels are not elevated in asymptomatic untreated HIV infection.

scholarly journals Intensifying Antiretroviral Therapy With Raltegravir and Maraviroc During Early Human Immunodeficiency Virus (HIV) Infection Does Not Accelerate HIV Reservoir Reduction

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Mario Ostrowski ◽  
Erika Benko ◽  
Feng Yun Yue ◽  
Connie J. Kim ◽  
Sanja Huibner ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Replication Competent Virus ◽  
Proviral Dna ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
Dna 2

Abstract Background.  Persistent human immunodeficiency virus (HIV) within the CD4+ T-cell reservoir is an obstacle to eradication. We hypothesized that adding raltegravir and maraviroc to standard combination antiretroviral therapy (cART) during early HIV infection could substantially reduce viral reservoirs as a step towards eradication. Methods.  A prospective, randomized, double-blinded, placebo-controlled pilot trial enrolled 32 participants with documented early (<6 months) HIV infection to either standard cART (emtricitabine/tenofovir/lopinavir/ritonavir) or intensive cART (standard regimen + raltegravir/maraviroc). Human immunodeficiency virus reservoirs were assessed at baseline and at 48 weeks by (1) proviral DNA, (2) cell-associated RNA, and (3) replication-competent virus, all from purified blood CD4+ T cells, and (4) gut proviral DNA. A multiassay algorithm (MAA) on baseline sera estimated timing of infection. Results.  Thirty individuals completed the study to the 48-week endpoint. The reduction in blood proviral burden was −1.03 log DNA copies/106 CD4+ T cells versus −.84 log in the standard and intensive groups, respectively (P = .056). Overall, there was no significant difference in the rate of decline of HIV-associated RNA, replication-competent virus in blood CD4+ T cells, nor proviral gut HIV DNA to 48 weeks. Individuals who presented with more recent HIV infection had significantly lower virus reservoirs, and cART tended to reduce their reservoirs to a greater extent. Conclusions.  Intensive cART led to no additional reduction in the blood virus reservoir at 48 weeks compared with standard cART. Human immunodeficiency virus reservoir size is smaller earlier in HIV infection. Other novel treatment strategies in combination with early cART will be needed to eliminate the HIV latent reservoir.

scholarly journals Impact of Biological Sex on Immune Activation and Frequency of the Latent HIV Reservoir During Suppressive Antiretroviral Therapy

2020 ◽  
Vol 222 (11) ◽  
pp. 1843-1852 ◽  
Author(s):  
Shane D Falcinelli ◽  
Bonnie E Shook-Sa ◽  
Morgan G Dewey ◽  
Sumati Sridhar ◽  
Jenna Read ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Immune Activation ◽  
Cd4 T Cells ◽  
Acute Infection ◽  
Interferon Response ◽  
Suppressive Therapy ◽  
Hiv Reservoir ◽  
Latent Hiv

Abstract Background Persistent HIV infection of long-lived resting CD4 T cells, despite antiretroviral therapy (ART), remains a barrier to HIV cure. Women have a more robust type 1 interferon response during HIV infection relative to men, contributing to lower initial plasma viremia. As lower viremia during acute infection is associated with reduced frequency of latent HIV infection, we hypothesized that women on ART would have a lower frequency of latent HIV compared to men. Methods ART-suppressed, HIV seropositive women (n = 22) were matched 1:1 to 22 of 39 ART-suppressed men. We also compared the 22 women to all 39 men, adjusting for age and race as covariates. We measured the frequency of latent HIV using the quantitative viral outgrowth assay, the intact proviral DNA assay, and total HIV gag DNA. We also performed activation/exhaustion immunophenotyping on peripheral blood mononuclear cells and quantified interferon-stimulated gene (ISG) expression in CD4 T cells. Results We did not observe evident sex differences in the frequency of persistent HIV in resting CD4 T cells. Immunophenotyping and CD4 T-cell ISG expression analysis revealed marginal differences across the sexes. Conclusions Differences in HIV reservoir frequency and immune activation appear to be small across sexes during long-term suppressive therapy.

Dysregulation of CD4+CD25+CD127lowFOXP3+ regulatory T cells in HIV-infected pregnant women

Blood ◽  
2011 ◽  
Vol 117 (6) ◽  
pp. 1861-1868 ◽  
Author(s):  
Lilian Kolte ◽  
Julie C. Gaardbo ◽  
Ingrid Karlsson ◽  
Anna Louise Sørensen ◽  
Lars P. Ryder ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Hiv Infection ◽  
Immune Activation ◽  
Lymphocyte Subsets ◽  
Peripheral Tolerance ◽  
Cd4 Counts ◽  
Thymic Output ◽  
Pregnancy And Postpartum ◽  
Hiv Negative

Abstract Pregnancy represents a major challenge to immunologic tolerance. How the fetal “semiallograft” evades maternal immune attack is unknown. Pregnancy success may involve alteration of both central (thymic) and peripheral tolerance mechanisms. HIV infection is characterized by CD4+ T-cell depletion, chronic immune activation, and altered lymphocyte subsets. We studied immunologic consequences of pregnancy in 20 HIV-infected women receiving highly active antiretroviral therapy (HAART), and for comparison in 16 HIV-negative women. Lymphocyte subsets, thymic output, and cytokine profiles were measured prospectively during pregnancy and postpartum. A significant expansion of CD4+CD25+CD127lowFoxP3+ regulatory T cells indicating alteration of peripheral tolerance was seen during second trimester, but only in HIV-negative women. HIV-infected women had lower CD4 counts, lower thymic output and Th-2 cytokines, and more immune activation at all time points compared with controls. Immune activation was decreased in HIV-infected patients during pregnancy. In contrast, CD4 counts were increased in both groups. In conclusion, the study does not indicate that pregnancy adversely affects the immunologic course of HIV infection. However, despite HAART during pregnancy, HIV-infected women display different immunologic profiles from HIV-negative women, which may have importance for the induction of fetal-maternal tolerance and in part explain the increased risk of abortion in HIV-infected women.

scholarly journals Composition of gut microbiota of children and adolescents with perinatal HIV infection taking antiretroviral therapy in Zimbabwe

2019 ◽  
Author(s):  
Trym T Flygel ◽  
Evgeniya Sovershaeva ◽  
Shantelle Classen-Weitz ◽  
Erik Hjerde ◽  
Kilaza S Mwaikono ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Gut Microbiota ◽  
Hiv Infection ◽  
Alpha Diversity ◽  
Illumina Miseq ◽  
Hiv Viral Load ◽  
Microbial Composition ◽  
Cross Sectional ◽  
Cd4 Counts ◽  
Perinatal Hiv

Abstract Background HIV infection causes impairment of the gastrointestinal barrier, with substantial depletion of CD4+ T-cells in the gut. Antiretroviral therapy (ART) restores CD4+ counts and may have beneficial effects on gut microbiota in adults. Little is known about effect of long-term ART on gut microbiome in HIV infected children. We investigated composition of gut microbiota in HIV infected and uninfected children and assessed associations between gut microbiota and patient characteristics. Methods In a cross-sectional study, rectal swabs were collected from 177 HIV infected and 103 HIV uninfected controls. Gut microbial composition was explored using 16S rRNA sequencing (Illumina Miseq). Results HIV infected children had significantly lower alpha-diversity and higher beta-diversity compared to HIV uninfected. No association was observed between microbiome diversity and CD4+ T-cell count, HIV viral load or HIV-associated chronic lung disease. We found enriched levels of Corynebacterium (p<0.01), Finegoldia (p<0.01) and Anaerococcus (p<0.01) in HIV infected, and enrichment of Enterobacteriaceae (p=0.02) in participants with low CD4+ counts (<400 cells/mm3). Prolonged ART-treatment (≥10 years) was significantly associated with a richer gut microbiota by alpha diversity. Conclusion HIV infected children have altered gut microbiota. Prolonged ART may restore the richness of the microbiota closer to that of HIV-uninfected children.

Renal Phosphate Handling in Antiretroviral-naïve HIV-infected Patients

2020 ◽  
Vol 20 ◽  
Author(s):  
Tewogbade Adeoye Adedeji ◽  
Simeon Adelani. Adebisi ◽  
Nife Olamide Adedeji ◽  
Olusola Akanni Jeje ◽  
Rotimi Samuel Owolabi
Keyword(s):  
Hiv Infection ◽  
Plasma Phosphate ◽  
Cross Sectional ◽  
Phosphate Retention ◽  
Significant Difference ◽  
Immunodeficiency Virus ◽  
Life Threatening ◽  
Moderate Chronic Kidney Disease ◽  
One Year ◽  
Sectional Analysis

Background: Human immunodeficiency virus (HIV) infection impairs renal function, thereby affecting renal phosphate metabolism. Objectives: We prospectively estimated the prevalence of phosphate abnormalities (mild, moderate to life-threatening hypophosphataemia, and hyperphosphataemia) before initiating antiretroviral therapy (ART). Methods: A cross-sectional analysis was performed on 170 consecutive newly diagnosed ART-naïve, HIV-infected patients attending our HIV/AIDS clinics over a period of one year. Fifty (50) screened HIV-negative blood donors were used for comparison (controls). Blood and urine were collected simultaneously for phosphate and creatinine assay to estimate fractional phosphate excretion (FEPi %) and glomerular filtration rate (eGFR). Results: eGFR showed significant difference between patients’ and controls’ medians (47.89ml/min/1.73m2 versus 60ml/min/1.73m2, p <0.001); which denotes a moderate chronic kidney disease in the patients. Of the 170 patients, 78 (45.9%) had normal plasma phosphate (0.6-1.4 mmol/L); 85 (50%) had hyperphosphataemia. Grades 1, 2 and 3 hypophosphataemia was observed in 3 (1.8%), 3 (1.8%), and 1(0.5%) patient(s) respectively. None had grade 4 hypophosphataemia. Overall, the patients had significantly higher median of plasma phosphate than the controls, 1.4 mmol/L (IQR: 1.0 – 2.2) versus 1.1 mmol/L (IQR: 0.3 – 1.6), p <0.001, implying hyperphosphataemia in the patients; significantly lower median urine phosphate than the controls, 1.5 mmol/L (IQR: 0.7 -2.1) versus 8.4 mmol/L (IQR: 3.4 – 16), p <0.001), justifying the hyperphosphataemia is from phosphate retention; but a non-significantly lower median FEPi% than the controls, 0.96 % (IQR: 0.3 -2.2) versus 1.4% (IQR: 1.2 -1.6), p > 0.05. Predictors of FEPi% were age (Odds ratio, OR 0.9, p = 0.009); weight (OR 2.0, p < 0.001); CD4+ cells count predicted urine phosphate among males (p = 0.029). Conclusion: HIV infection likely induces renal insufficiency with reduced renal phosphate clearance. Thus, hyperphosphataemia is highly prevalent, and there is mild to moderate hypophosphataemia but its life-threatening form (grade 4) is rare among ART-naïve HIV patients.

scholarly journals Anolunula in Fingernails among Patients Infected with HIV

2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Pratik Gahalaut ◽  
Nitin Mishra ◽  
Sandhya Chauhan ◽  
Mir Mubashir Ali ◽  
Madhur Kant Rastogi ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Cross Sectional Study ◽  
Negative Control ◽  
Hiv Positive ◽  
Control Group ◽  
Cross Sectional ◽  
Significant Difference ◽  
Stage 1 ◽  
And Control ◽  
Hiv Negative

Lunula is the white, half-moon shaped area seen in proximal ends of some nails. Though a few studies have described the nail changes that can occur in association with HIV infection, none of these paid much attention to lunula. Aims and Objectives. To study the lunula in fingernails among HIV infected patients. Materials and Methods. An observational, cross-sectional study to record presence of lunula in 168 HIV-positive patients and compare it with age and sex matched 168 healthy HIV-negative control. Anolunula (absence of lunula) in HIV-positive patients was correlated with CD4 counts, stages of HIV infection, time since patient was diagnosed as HIV-positive, and status of antiretroviral therapy. Results. Anolunula was present in significantly more fingernails in HIV-positive patients compared to HIV-negative controls. There was a highly significant difference for total anolunula (anolunula in all fingernails) in study and control group. Incidence of total anolunula was directly proportional to the stage of HIV infection, increasing progressively as the HIV infection advances from stage 1 to stage 4. Conclusion. Absence of lunula is related to not only HIV infection per se but also the stages of HIV infection.

Thyroid hormone suppression in feeder pigs following polymicrobial or porcine reproductive and respiratory syndrome virus-2 challenge

2021 ◽  
Author(s):  
J Alex Pasternak ◽  
Daniel J MacPhee ◽  
Joan K Lunney ◽  
Raymond R R Rowland ◽  
PigGen Canada ◽  
...  
Keyword(s):  
Viral Load ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Average Daily Gain ◽  
Respiratory Syndrome Virus ◽  
Post Inoculation ◽  
Serum Samples ◽  
Cross Sectional ◽  
Post Exposure ◽  
Daily Gain

Abstract Thyroid hormones are powerful regulators of growth, development and basal metabolic rate and can be dysregulated under conditions of severe stress or illness. To understand the role of these hormones in porcine disease response, serum samples were obtained from 3 batches of nursery-aged pigs (n=208) exposed to a natural polymicrobial disease challenge with an array of bacterial and viral pathogens. Levels of total thyroxin (T4) and triiodothyronine (T3) assessed in sera by radioimmunoassay (RIA), decreased significantly by 14 days post exposure (DPE). Levels of T3 partially rebounded by 48 DPE, while T4 levels remain depressed. Post-exposure T3 and T4 levels were positively correlated with acute and long-term average daily gain. Cross-sectional sampling of animals maintained at the high health source farms, showed no equivalent change in either hormone when managed under standard industry conditions. To further elucidate the effect of PRRSV-infection on thyroid hormone levels, archived sera over 42 days post inoculation (DPI) from nursery pigs (N=190) challenged with one of two PRRSV2 strains by the PRRS Host Genetics Consortium (PHGC) were similarly assessed, with animals selected in a two-by-two design, to investigate biological extremes in average daily gain (ADG) and viral load. All animals showed a similar decrease in both thyroid hormones reaching a minimum at 7 DPI and returning to near pre challenge levels by 42 DPI. Post challenge T3 and T4 levels were significantly greater in high ADG groups, with no significant association with viral load or strain. The results of this study demonstrate porcine susceptibility to thyroid disruption in response to disease challenge and demonstrate a relationship between this response and growth performance.

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