Dataset Information

SARS-CoV-2 Vaccine-Induced T-Cell Response after Three Doses in People Living with HIV on Antiretroviral Therapy Compared to Seronegative Controls (CTN 328 COVAXHIV Study).

ABSTRACT: People living with HIV (PLWH) may be at risk for poor immunogenicity to certain vaccines, including the ability to develop immunological memory. Here, we assessed T-cell immunogenicity following three SARS-CoV-2 vaccine doses in PLWH versus uninfected controls. Blood was collected from 38 PLWH on antiretroviral therapy and 24 age-matched HIV-negative controls, pre-vaccination and after 1st/2nd/3rd dose of SARS-CoV-2 vaccines, without prior SARS-CoV-2 infection. Flow cytometry was used to assess ex vivo T-cell immunophenotypes and intracellular Tumor necrosis factor (TNF)-α/interferon(IFN)-γ/interleukin(IL)-2 following SARS-CoV-2-Spike-peptide stimulation. Comparisons were made using Wilcoxon signed-rank test for paired variables and Mann-Whitney for unpaired. In PLWH, Spike-specific CD4 T-cell frequencies plateaued post-2nd dose, with no significant differences in polyfunctional SARS-CoV-2-specific T-cell proportions between PLWH and uninfected controls post-3rd dose. PLWH had higher frequencies of TNFα+CD4 T-cells and lower frequencies of IFNγ+CD8 T-cells than seronegative participants post-3rd dose. Regardless of HIV status, an increase in naive, regulatory, and PD1+ T-cell frequencies was observed post-3rd dose. In summary, two doses of SARS-CoV-2 vaccine induced a robust T-cell immune response in PLWH, which was maintained after the 3rd dose, with no significant differences in polyfunctional SARS-CoV-2-specific T-cell proportions between PLWH and uninfected controls post-3rd dose.

SUBMITTER: Alexandrova Y

PROVIDER: S-EPMC9959053 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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SARS-CoV-2 Vaccine-Induced T-Cell Response after Three Doses in People Living with HIV on Antiretroviral Therapy Compared to Seronegative Controls (CTN 328 COVAXHIV Study).

Alexandrova Yulia Y Yero Alexis A Mboumba Bouassa Ralph-Sydney RS Comeau Eve E Samarani Suzanne S Brumme Zabrina L ZL Hull Mark M Crawley Angela M AM Langlois Marc-André MA Angel Jonathan B JB Cooper Curtis L CL Needham Judy J Lee Terry T Singer Joel J Anis Aslam H AH Costiniuk Cecilia T CT Jenabian Mohammad-Ali MA

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People living with HIV (PLWH) may be at risk for poor immunogenicity to certain vaccines, including the ability to develop immunological memory. Here, we assessed T-cell immunogenicity following three SARS-CoV-2 vaccine doses in PLWH versus uninfected controls. Blood was collected from 38 PLWH on antiretroviral therapy and 24 age-matched HIV-negative controls, pre-vaccination and after 1st/2nd/3rd dose of SARS-CoV-2 vaccines, without prior SARS-CoV-2 infection. Flow cytometry was used to assess ...[more]

PMID: 36851789

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Project description:IntroductionMost existing vaccines require higher or additional doses or adjuvants to provide similar protection for people living with HIV (PLWH) compared with HIV-uninfected individuals. Additional research is necessary to inform COVID-19 vaccine use in PLWH.Methods and analysisThis multicentred observational Canadian cohort study will enrol 400 PLWH aged >16 years from Montreal, Ottawa, Toronto and Vancouver. Subpopulations of PLWH of interest will include individuals: (1) >55 years of age; (2) with CD4 counts <350 cells/mm3; (3) with multimorbidity (>2 comorbidities) and (4) 'stable' or 'reference' PLWH (CD4 T cells >350 cells/mm3, suppressed viral load for >6 months and <1 comorbidity). Data for 1000 HIV-negative controls will be obtained via a parallel cohort study (Stop the Spread Ottawa), using similar time points and methods. Participants receiving >1 COVID-19 vaccine will attend five visits: prevaccination; 1 month following the first vaccine dose; and at 3, 6 and 12 months following the second vaccine dose. The primary end point will be the percentage of PLWH with COVID-19-specific antibodies at 6 months following the second vaccine dose. Humoral and cell-mediated immune responses, and the interplay between T cell phenotypes and inflammatory markers, will be described. Regression techniques will be used to compare COVID-19-specific immune responses to determine whether there are differences between the 'unstable' PLWH group (CD4 <350 cells/mm3), the stable PLWH cohort and the HIV-negative controls, adjusting for factors believed to be associated with immune response. Unadjusted analyses will reveal whether there are differences in driving factors associated with group membership.Ethics and disseminationResearch ethics boards at all participating institutions have granted ethics approval for this study. Written informed consent will be obtained from all study participants prior to enrolment. The findings will inform the design of future COVID-19 clinical trials, dosing strategies aimed to improve immune responses and guideline development for PLWH.Trial registration numberNCT04894448.

Project description:ObjectivesIn late 2014, an HIV outbreak occurred in rural Cambodia among villagers who received medical injections from unlicensed medical providers, justifying the need to assess medical injection practices among those who are at risk of acquiring and/or transmitting HIV. This study examined medical injection/infusion behaviours among people living with HIV (PLWH) and those who were HIV negative in Cambodia. These behaviours should be properly assessed, especially among PLWH, as their prevalence might influence a future risk of other outbreaks.DesignA cross-sectional survey was conducted in order to examine injection behaviours and estimate injection prevalence and rates by HIV status. Unsafe injections/infusions were those received from village providers who do not work at a health centre or hospital, or traditional providers at the participant's (self-injection included) or provider's home. Logistic regression was performed to examine the relationship between unsafe injection/infusion and HIV, adjusting for sex, age, education, occupation, residence location and other risk factors.SettingThe survey was conducted in 10 HIV testing and treatment hospitals/clinics across selected provinces in Cambodia, from February to March 2017.ParticipantsA total number of 500 volunteers participated in the survey, 250 PLWH and 250 HIV-negative individuals.Outcome measuresMeasures of injection prevalence and other risk behaviours were based on self-reports.ResultsBoth groups of participants reported similar past year's injection/infusion use, 47% (n=66) among PLWH and 54% (n=110) HIV-negative participants (p=0.24). However, 15% (n=11) of PLWH reported having received unsafe last injection compared with only 7% (n=11) of HIV-negative participants. In logistic regression, this association remained numerically positive, but was not statistically significant (adjusted OR 1.84 (95% CI: 0.71 to 4.80)).ConclusionsThe inclination for medical injections and infusions (unsafe at times) among PLWH and the general population in Cambodia was common and could possibly represent yet another opportunity for parenteral transmission outbreak.

Project description:ObjectiveLimited data exist regarding the immune benefits of fourth COVID-19 vaccine doses in people with HIV (PWH) receiving antiretroviral therapy (ART), particularly now that most have experienced a SARS-CoV-2 infection. We quantified wild-type, Omicron-BA.5 and Omicron-BQ.1-specific neutralization up to 1 month post-fourth COVID-19 vaccine dose in 63 (19 SARS-CoV-2-naive and 44 SARS-CoV-2-experienced) PWH.DesignA longitudinal observational cohort.MethodsQuantification of wild-type-, Omicron-BA.5, and Omicron-BQ.1-specific neutralization using live virus assays.ResultsParticipants received monovalent (44%) and bivalent (56%) mRNA fourth doses. In COVID-19-naive PWH, fourth doses enhanced wild-type and Omicron-BA.5-specific neutralization modestly above three-dose levels ( P = 0.1). In COVID-19-experienced PWH, fourth doses enhanced wild-type specific neutralization modestly ( P = 0.1) and BA.5-specific neutralization substantially ( P = 0.002). Consistent with humoral benefits of 'hybrid' immunity, COVID-19-experienced PWH exhibited the highest neutralization post-fourth dose, wherein those with Omicron-era infections displayed higher wild-type specific ( P = 0.04) but similar BA.5 and BQ.1-specific neutralization than those with pre-Omicron-era infections. Nevertheless, BA.5-specific neutralization was significantly below wild-type in everyone regardless of COVID-19 experience, with BQ.1-specific neutralization lower still (both P < 0.0001). In multivariable analyses, fourth dose valency did not affect neutralization magnitude. Rather, an mRNA-1273 fourth dose (versus a BNT162b2 one) was the strongest correlate of wild-type specific neutralization, while prior COVID-19, regardless of pandemic era, was the strongest correlate of BA.5 and BQ.1-specific neutralization post-fourth dose.ConclusionFourth COVID-19 vaccine doses, irrespective of valency, benefit PWH regardless of prior SARS-CoV-2 infection. Results support recommendations that all adults receive a fourth COVID-19 vaccine dose within 6 months of their third dose (or their most recent SARS-CoV-2 infection).

Project description:IntroductionDespite antiretroviral therapy (ART), people living with HIV have higher rates of non-infectious chronic diseases. These conditions are driven by relatively high levels of inflammation persisting on ART compared with uninfected individuals. Chronic inflammation also contributes to HIV persistence during ART. Cannabis when taken orally may represent a way to reduce inflammation and strengthen immune responses. Before planning large interventional studies, it is important to ensure that cannabis taken orally is safe and well tolerated in people living with HIV. We propose to conduct a pilot randomised trial to examine the safety and tolerability of cannabis oils containing tetrahydrocannabinol (THC) and cannabidiol (CBD) consumed orally in people living with HIV. We will also measure inflammatory markers, markers of HIV persistence in peripheral blood cells and changes in the gastrointestinal microbiome.Methods and analysisTwenty-six people living with HIV having undetectable viral load for at least 3 years will be randomised to receive TN-TC11LM (THC:CBD in 1:1 ratio) or TN-TC19LM (THC:CBD in 1:9 ratio) capsules daily for 12 weeks. Safety and tolerability of these capsules will be assessed through haematological, hepatic and renal blood tests, face-to-face interviews and questionnaires. Proportions of participants without any signs of significant toxicity (grades 0-2 scores on the WHO toxicity scale) and who complete the study, as well as scores on quality of life and mood will be examined using descriptive statistics. The effects on inflammatory markers, markers of peripheral blood reservoir size and effect on the composition of the gastrointestinal microbiome will be assessed before and after study completion.Ethics and disseminationThis study has been approved by the Research Institute of the McGill University Health Centre. A Data Safety Monitor will review safety information at regular intervals. The final manuscript will be submitted to an open-access journal within 6 months of study completion.Trial registration numberNCT03550352.

Project description:BackgroundDespite antiretroviral therapy (ART) being widely available, HIV continues to cause substantial illness and premature death in low-and-middle-income countries. High rates of loss to follow-up after HIV diagnosis can delay people starting ART. Starting ART within seven days of HIV diagnosis (rapid ART initiation) could reduce loss to follow-up, improve virological suppression rates, and reduce mortality.ObjectivesTo assess the effects of interventions for rapid initiation of ART (defined as offering ART within seven days of HIV diagnosis) on treatment outcomes and mortality in people living with HIV. We also aimed to describe the characteristics of rapid ART interventions used in the included studies.Search methodsWe searched CENTRAL, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, and four other databases up to 14 August 2018. There was no restriction on date, language, or publication status. We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and websites for unpublished literature, including conference abstracts.Selection criteriaWe included randomized controlled trials (RCTs) that compared rapid ART versus standard care in people living with HIV. Children, adults, and adolescents from any setting were eligible for inclusion.Data collection and analysisTwo review authors independently assessed the eligibility of the studies identified in the search, assessed the risk of bias and extracted data. The primary outcomes were mortality and virological suppression at 12 months. We have presented all outcomes using risk ratios (RR), with 95% confidence intervals (CIs). Where appropriate, we pooled the results in meta-analysis. We assessed the certainty of the evidence using the GRADE approach.Main resultsWe included seven studies with 18,011 participants in the review. All studies were carried out in low- and middle-income countries in adults aged 18 years old or older. Only one study included pregnant women.In all the studies, the rapid ART intervention was offered as part of a package that included several cointerventions targeting individuals, health workers and health system processes delivered alongside rapid ART that aimed to facilitate uptake and adherence to ART.Comparing rapid ART with standard initiation probably results in greater viral suppression at 12 months (RR 1.18, 95% CI 1.10 to 1.27; 2719 participants, 4 studies; moderate-certainty evidence) and better ART uptake at 12 months (RR 1.09, 95% CI 1.06 to 1.12; 3713 participants, 4 studies; moderate-certainty evidence), and may improve retention in care at 12 months (RR 1.22, 95% CI 1.11 to 1.35; 5001 participants, 6 studies; low-certainty evidence). Rapid ART initiation was associated with a lower mortality estimate, however the CIs included no effect when compared to standard of care (RR 0.72, 95% CI 0.51 to 1.01; 5451 participants, 7 studies; very low-certainty evidence). It is uncertain whether rapid ART has an effect on modification of ART treatment regimens as data are lacking (RR 7.89, 95% CI 0.76 to 81.74; 977 participants, 2 studies; very low-certainty evidence). There was insufficient evidence to draw conclusions on the occurrence of adverse events.Authors' conclusionsRCTs that include initiation of ART within one week of diagnosis appear to improve outcomes across the HIV treatment cascade in low- and middle-income settings. The studies demonstrating these effects delivered rapid ART combined with several setting-specific cointerventions. This highlights the need for pragmatic research to identify feasible packages that assure the effects seen in the trials when delivered through complex health systems.

Dataset Information

SARS-CoV-2 Vaccine-Induced T-Cell Response after Three Doses in People Living with HIV on Antiretroviral Therapy Compared to Seronegative Controls (CTN 328 COVAXHIV Study).

Publications

SARS-CoV-2 Vaccine-Induced T-Cell Response after Three Doses in People Living with HIV on Antiretroviral Therapy Compared to Seronegative Controls (CTN 328 COVAXHIV Study).

Similar Datasets

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