Immune restoration in HIV-1-infected patients after 12 years of antiretroviral therapy: a real-world observational study.
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ABSTRACT:
SUBMITTER: Liu J
PROVIDER: S-EPMC7733958 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In people with HIV (PWH), the post antiretroviral therapy (ART) window is critical for immune restoration and HIV reservoir stabilization. We employ deep immune profiling, T cell receptor (TCR) sequencing and examine proliferation to assess how ART impacts T cell homeostasis. Hierarchies and frequencies of dominant CD4 TCR clonotypes (0.1-11% of all CD4+ T cells) remain stable post-ART, suggesting that clonal homeostasis can be independent of homeostatic processes regulating CD4+T cell absolute number, phenotypes and function. The slow restoration of host-immunity post-ART also has implications for the design of ART interruption studies.
2023-10-09 | GSE244867 | GEO
Project description:ObjectiveTo provide estimates of HIV-free survival at 12-24 months in breastfed children by maternal ART (6 months or lifelong) to inform WHO HIV and Infant Feeding guidelines.MethodsEighteen studies published 2005-2015 were included in a systematic literature review (1295 papers identified, 156 abstracts screened, 55 full texts); papers were analysed by narrative synthesis and meta-analysis of HIV-free survival by maternal ART regimen in a random effects model. We also grouped studies by feeding modality. Study quality was assessed using a modified Newcastle-Ottawa Scale (NOS) and GRADE.ResultsThe pooled estimates for 12-month HIV-free survival were 89.8% (95% confidence interval, CI: 86.5%, 93.2%) for infants of mothers on ART for 6 months post-natally (six studies) and 91.4% (95% CI 87.5%, 95.4%) for infants of mothers on lifelong ART (three studies). Eighteen-month HIV-free survival estimates were 89.0% (95% CI 83.9%, 94.2%) with 6 months ART (five studies) and 96.1% (95% CI 92.8%, 99.0%) with lifelong ART (three studies). Twenty-four-month HIV-free survival for infants whose mothers were on ART to 6 months post-natally (two studies) was 89.2% (95% CI 79.9%, 98.5%). Heterogeneity was considerable throughout. In four studies, HIV-free survival in breastfed infants ranged from 87% (95% CI 78%, 92%) to 96% (95% CI 91%, 98%) and in formula-fed infants from 67% (95% CI 35.5%, 87.9%) to 97.6% (95% CI 93.0%, 98.2%).ConclusionOur results highlight the importance of breastfeeding for infant survival and of ART in reducing the risk of mother-to-child HIV transmission and support the WHO recommendation to initiate ART for life immediately after HIV diagnosis.
| S-EPMC5096069 | biostudies-literature
Project description:IntroductionRecent changes in antiretroviral therapies (ARTs) may have affected medication adherence of people living with human immunodeficiency virus-1 (HIV-1). In this study adherence to ART regimens among patients with HIV-1 (PWH) across the US during a recent time period was examined and study findings were stratified by US region and state.MethodsA retrospective observational study using the Symphony Health Solution Integrated Dataverse database was conducted. Patients ≥ 18 years of age who had a diagnosis of HIV-1 (without an HIV-2 diagnosis) and who were treated with ART between July 2017 and September 2018 (first pharmacy record: index date) were selected from the data source. Both patients who had not been previously treated with ART and those who were treatment experienced were included. Patients were required to have ≥ 1 medical/pharmacy record ≥ 12 months after their index date (follow-up period). Patient characteristics were examined during a 12-month pre-index period. During the follow-up, medication adherence, measured as the proportion of days covered (PDC), was examined for all patients and stratified by US region and state.ResultsAmong 206,474 adult PWH treated with ART, mean age was 47.9 years, 73.4% were male, and 30.0% were Caucasian. The most prevalent comorbid conditions were hyperlipidemia (25.1%), depressive disorders (14.8%), and type 2 diabetes (12.1%). During the follow-up period, mean (standard deviation) PDC was 74.1% (25.9%) among PWH across the US [Midwest: 74.4% (25.5%); Northeast: 74.3% (26.1%); South: 73.2% (26.3%); West: 76.4% (24.8%)]. Across all US regions, > 60% of PWH had adherence < 90% and > 40% had adherence < 80%; the West had the highest adherent population.ConclusionsAmong PWH treated with ART across the US, a majority had suboptimal adherence. Implementation of strategies to improve ART adherence, including clinical consideration of ARTs with high genetic barriers to resistance, is needed in the US.
| S-EPMC8363866 | biostudies-literature
Project description:Background/Aims:Little is known about the national colonoscopy volume in Asian countries. This study aimed to assess the national colonoscopy volume in Korea over a 12-year period on the basis of a nationwide population-based database. Methods:We conducted a population-based study for colonoscopy claims (14,511,158 colonoscopies performed on 13,219,781 patients) on the basis of the Korean National Health Insurance Service database from 2002 to 2013. The 12-year national colonoscopy burden was analyzed according to patient age, patient sex, and healthcare facility type. Results:The overall volume of colonoscopy increased 8-fold over the 12-year period. The annual colonoscopic polypectomy rate significantly increased in all patient sex and age groups over the 12-years period (all p<0.001). The yearly colonoscopic polypectomy rate for men was significantly increased compared with that for women (2.3% vs 1.7%, p<0.001) and for the screening-age group compared with that for the young-age group (2.0% vs 1.6%, p<0.001). The yearly colonoscopic polypectomy rate relative to the total colonoscopy volume significantly increased in primary, secondary, and tertiary facilities by 2.4%, 1.9%, and 1.4% during the 12-year period (all p<0.001). In addition, the annual colonoscopy volume covered by high-volume facilities significantly increased by 1.8% in primary healthcare facilities over the 12-year period (p<0.001). Conclusions:Healthcare resources should be prioritized to allow adequate colonoscopic capacity, especially for men, individuals in the screening-age group, and at primary healthcare facilities. Cost-effective strategies to improve the quality of colonoscopy may focus on primary healthcare facilities and high-volume facilities in Korea.
| S-EPMC7234886 | biostudies-literature
Project description:ObjectiveTo evaluate potential adverse associations of individual antiretroviral medications used in combination antiretroviral therapy regimens on cardiac structure and function in youth with perinatally-acquired HIV infection (PHIV).DesignPHIV youth (N = 325) enrolled in a prospective multisite cohort study had a single echocardiogram at age 7-16 years to evaluate cardiac function and structure.MethodsWe applied several statistical approaches to evaluate associations between use of 18 individual antiretroviral medications with Z-scores for 11 measures of left ventricular function and structure. These included simultaneously evaluating all antiretroviral medications in adjusted linear regression models controlling for the false discovery rate (FDR), applying hierarchical models to estimate individual antiretroviral medication effects as deviations from drug class means, and evaluating latent measures of cardiac function and structure underlying multiple echocardiographic parameters.ResultsYouth taking combination regimens with a protease inhibitor (69%) had significantly better cardiac function than those on other regimens. After FDR control and adjustment for other antiretroviral medications, no individual antiretroviral medication was significantly associated with any measure of left ventricular function, but zidovudine was associated with higher adjusted mean Z-scores for one measure of left ventricular structure (end-systolic wall stress). Factor analysis identified three latent factors: heart function, heart size, and heart wall stress. Lopinavir was associated with better heart function scores, whereas zidovudine was associated with higher wall stress scores. Zidovudine and nevirapine were associated with higher heart size factor scores.ConclusionsDespite cardioprotective effects of combination regimens in PHIV youth, individual antiretroviral medications were associated with altered cardiac structure, which could progress to symptomatic cardiomyopathy in adulthood.
| S-EPMC6519135 | biostudies-literature
Project description:BackgroundTo access the long term relationship between efavirenz plasma concentrations and evolution of HIV RNA loads and CD4 cell counts in children.MethodsRetrospective analysis of data from HIV-infected children on first line efavirenz-containing regimen. A population pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the evolution of HIV RNA load and CD4 cell count (efficacy outcomes) in relation to efavirenz plasma concentration. Individual CYP2B6 516 G>T genotype data were not available for this analysis. A score (ISEFV) quantifying the effect of efavirenz concentrations on the long-term HIV replication was calculated from efavirenz concentrations and PD parameters and, a value of ISEFV below which HIV replication is likely not suppressed was determined. Cox proportional hazards regression models were used to assess the association of the risk of viral replication with ISEFV, and with efavirenz mid-dose concentration(C12).ResultsAt treatment initiation, median (interquartile range, IQR) age was 8 years (5 to 10), body weight 17 kg (14 to 23), HIV RNA load 5.1 log10 copies/mL (4.6 to 5.4), and CD4 cell count 71 cells/mm3. A model of PK-PD viral dynamics assuming that efavirenz decreases the rate of infected host cells adequately described the relationship of interest. After adjusting for age, baseline HIV RNA load and CD4 cell counts an ISEFV <85% was significantly associated with a higher risk of viral replication (p-value <0.001) while no significant association was observed with C12 <1.0 mg/L.ConclusionThe ISEFV score was a good predictor of viral replication in children on efavirenz-based treatment.
| S-EPMC6521995 | biostudies-literature
Project description:Treatment outcomes of HIV patients receiving antiretroviral therapy (ART) in Rwanda are scarcely documented. HIV viral load (VL) and HIV drug-resistance (HIVDR) outcomes at month 12 were determined in a prospective cohort study of antiretroviral-naïve HIV patients initiating first-line therapy in Kigali. Treatment response was monitored clinically and by regular CD4 counts and targeted HIV viral load (VL) to confirm drug failure. VL measurements and HIVDR genotyping were performed retrospectively on baseline and month 12 samples. One hundred and fifty-eight participants who completed their month 12 follow-up visit had VL data available at month 12. Most of them (88%) were virologically suppressed (VL?1000 copies/mL) but 18 had virological failure (11%), which is in the range of WHO-suggested targets for HIVDR prevention. If only CD4 criteria had been used to classify treatment response, 26% of the participants would have been misclassified as treatment failure. Pre-therapy HIVDR was documented in 4 of 109 participants (3.6%) with an HIVDR genotyping results at baseline. Eight of 12 participants (66.7%) with virological failure and HIVDR genotyping results at month 12 were found to harbor mutation(s), mostly NNRTI resistance mutations, whereas 4 patients had no HIVDR mutations. Almost half (44%) of the participants initiated ART at CD4 count ?200 cell/µl and severe CD4 depletion at baseline (<50 cells/µl) was associated with virological treatment failure (p?=?0.008). Although the findings may not be generalizable to all HIV patients in Rwanda, our data suggest that first-line ART regimen changes are currently not warranted. However, the accumulation of acquired HIVDR mutations in some participants underscores the need to reinforce HIVDR prevention strategies, such as increasing the availability and appropriate use of VL testing to monitor ART response, ensuring high quality adherence counseling, and promoting earlier identification of HIV patients and enrollment into HIV care and treatment programs.
| S-EPMC3741294 | biostudies-literature
Project description:BackgroundHuman immunodeficiency virus (HIV) infection and associated immune activation predict the risk of cardiovascular disease in resource-rich areas. Less is known about these relationships in sub-Saharan Africa.MethodsBeginning in 2005, we enrolled subjects in southwestern Uganda into a cohort at the time of antiretroviral therapy (ART) initiation. Multiple immune activation measures were assessed before and 6 months after ART initiation. Beginning in 2013, participants aged >40 years underwent metabolic profiling, including measurement of hemoglobin A1c and lipid levels and carotid ultrasonography. We fit regression models to identify traditional and HIV-specific correlates of common carotid intima media thickness (CCIMT).ResultsA total of 105 participants completed carotid ultrasonography, with a median completion time of 7 years following ART initiation. Age, low-density lipoprotein cholesterol level, and pre-ART HIV load were correlated with CCIMT. No association was found between CCIMT and any pre-ART biomarkers of immune activation. However, in multivariable models adjusted for cardiovascular disease risk factors, lower absolute levels of soluble CD14 and interleukin 6 and greater declines in the CD14 level and kynurenine-tryptophan ratio after 6 months of ART predicted a lower CCIMT years later (P < .01).ConclusionsPersistent immune activation despite ART-mediated viral suppression predicts the future atherosclerotic burden among HIV-infected Ugandans. Future work should focus on clinical correlates of these relationships, to elucidate the long-term health priorities for HIV-infected people in the region.
| S-EPMC4704672 | biostudies-literature
Project description:ObjectivesTo determine the incidence, clinical manifestations and risk factors for immune reconstitution inflammatory syndrome (IRIS) in young children initiating highly active antiretroviral therapy (HAART).DesignA prospective cohort of antiretroviral-naïve HIV-infected children less than 24 months of age enrolled in a treatment strategies trial in Johannesburg, South Africa.MethodsAmong 169 HIV-infected children initiating HAART, April 2005 to November 2006, the records of 83 children suspected to have IRIS within 6 months of starting treatment were reviewed to determine whether they met criteria for IRIS. Seven were excluded due to incomplete follow-up. Pretreatment and post-treatment characteristics of children with and without IRIS were compared.ResultsOverall, 34/162 (21%) children developed IRIS at a median of 16 days (range 7-115 days) post-HAART initiation. Bacille Calmette-Guérin reaction was most common occurring in 24/34 (71%) children, primarily injection site lesions and/or ipsilateral axillary lymphadenitis with abscess. Other IRIS conditions (not mutually exclusive) included Mycobacterium tuberculosis (n = 12), cytomegalovirus pneumonia (n = 1), Streptococcus pneumonia sepsis (n = 1), and severe seborrheic dermatitis (n = 1). Children with IRIS were younger (median age 7 vs. 10 months, P = 0.007) with a lower CD4 cell percentage (median 13.9 vs. 19.2, P = 0.009) at HAART initiation than controls. After 24 weeks on HAART, 62% of IRIS cases vs. 28% of controls had HIV RNA more than 400 copies/ml (P = 0.001), odds ratio = 2.88 (95% confidence interval = 1.14-7.29) after adjusting for baseline factors.ConclusionInfants and young children with advanced HIV disease initiating HAART are at high risk for developing IRIS, leading to additional morbidity and possibly impairing virologic response to antiretroviral treatment.
| S-EPMC2810152 | biostudies-literature
Project description:Immune checkpoint molecules (ICMs) regulate T cell responses. In chronic viral infections and cancer, where antigens can persistently stimulate the immune system, ICMs can serve as a barrier to effective immune responses. The role of ICMs in the setting of systemic low-grade inflammation as in aging and antiretroviral therapy (ART)-suppressed HIV infection is not known. In this study, we made use of stored samples from the FLORAH cohort of HIV-infected ART-suppressed adults (age range 19-77 years.) and age-matched HIV-uninfected controls. We measured the expression levels of ICMs: PD-1, LAG-3, TIGIT, TIM-3, and 2B4 on resting CD4 and CD8 T cells and maturation subsets. To determine how expression of these molecules can affect T cell function, we stimulated peripheral blood mononuclear cell with HIV Gag or p09/H1N1 antigen and performed intracellular cytokine staining by multiparameter flow cytometry. ICMs were expressed at higher levels in CD8 compared with CD4. PD-1 was the only molecule that remained significantly higher in HIV-infected individuals compared with controls. LAG-3 expression increased with age in CD4 and CD8 T cells. 2B4 expression on CD8 T cells was negatively associated with IL-2 production but showed no effect on CD4 T cell function. TIM-3 expression was negatively associated with IL-21 production in CD4 and CD8 T cells and also negatively correlated with flu vaccine responses in HIV-negative individuals. Taken altogether, this study demonstrates the marked variation in ICM expression in T cells among adults and sheds light on the biology of these molecules and their effects on antigen-specific T cell functions. Overall, our results point to TIM-3 as a potential biomarker for immune function in HIV+ individuals on ART.
| S-EPMC6862963 | biostudies-literature