Trial reportPloS one2008
Metabolic and immune activation effects of treatment interruption in chronic HIV-1 infection: implications for cardiovascular risk.
Trial report in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00015704 (An Open-Label, Pilot Study Utilizing CD4 T-Cell Counts Lower Than 350 Cells/mm3 as the Threshold for Restarting Therapy With Potent Antiretroviral Therapy With or Without Interleukin-2 to Determine the Effect of Pulse Therapy on the Characteristics of Treatment Interruptions), which is not on this map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-Label, Pilot Study Utilizing CD4 T-Cell Counts Lower Than 350 Cells/mm3 as the Threshold for Restarting Therapy With Potent Antiretroviral Therapy With or Without Interleukin-2 to Determine the Effect of Pulse Therapy on the Characteristics of Treatment Interruptions
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Systematic review on cumulative HIV viraemia among people living with HIV receiving antiretroviral treatment and its association with mortality and morbidity.International health · 2024Pooled it
- Dipeptidyl peptidase IV inhibition does not adversely affect immune or virological status in HIV infected men and women: a pilot safety study.The Journal of clinical endocrinology and metabolism · 2013Trial
- Changes in lipids and lipoprotein particle concentrations after interruption of antiretroviral therapy.Journal of acquired immune deficiency syndromes (1999) · 2010Trial
- The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters.AIDS (London, England) · 2010Trial
- Inferiority of IL-2 alone versus IL-2 with HAART in maintaining CD4 T cell counts during HAART interruption: a randomized controlled trial.AIDS (London, England) · 2009Trial
- Evaluating the use of antiviral drugs in HIV patients with cardiovascular diseases and how to reduce the incidence of cardiac events in these patients.American journal of cardiovascular disease · 2024Review
- Cumulative HIV Viremia Copy-Years and Hypertension in People Living with HIV.Current HIV research · 2020Article
- Virologic suppression and CD4+ cell count recovery after initiation of raltegravir or efavirenz-containing HIV treatment regimens.AIDS (London, England) · 2018Observational
- Integrative Analysis of Immunological Data to Explore Chronic Immune T-Cell Activation in Successfully Treated HIV Patients.PloS one · 2017Article
- Pathophysiology and management of cardiovascular disease in patients with HIV.The lancet. Diabetes & endocrinology · 2016Review
- Inflammatory Markers Associated With Subclinical Coronary Artery Disease: The Multicenter AIDS Cohort Study.Journal of the American Heart Association · 2016Article
- Risk of coronary heart disease in patients with HIV infection.Nature reviews. Cardiology · 2014Review
- Association between latent proviral characteristics and immune activation in antiretrovirus-treated human immunodeficiency virus type 1-infected adults.Journal of virology · 2014Article
- Immune activation and collateral damage in AIDS pathogenesis.Frontiers in immunology · 2013Review
- Effects of human immunodeficiency virus on the erythrocyte and megakaryocyte lineages.World journal of virology · 2013Review
- Prevalence of cardiovascular diseases in HIV-infected outpatients: results from a prospective, multicenter cohort study.Clinical research in cardiology : official journal of the German Cardiac Society · 2013Article
- HIV disease activity as a modulator of lipoprotein(a) and allele-specific apolipoprotein(a) levels.Arteriosclerosis, thrombosis, and vascular biology · 2013Article
- Second-line protease inhibitor-based HAART after failing non-nucleoside reverse transcriptase inhibitor-based regimens in Asian HIV-infected children.Antiviral therapy · 2013Article
- HIV-specific immune dysregulation and atherosclerosis.Current HIV/AIDS reports · 2012Review
- Novel clinical trial designs for the development of new antiretroviral agents.AIDS (London, England) · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 9 institutions in 2 countries.
Funding
Abstract
backgroundConcern about costs and antiretroviral therapy (ART)-associated toxicities led to the consideration of CD4 driven strategies for the management of HIV. That approach was evaluated in the SMART trial that reported an unexpected increase of cardiovascular events after treatment interruption (TI). Our goal was to evaluate fasting metabolic changes associated with interruption of antiretroviral therapy and relate them to changes of immune activation markers and cardiovascular risk. METHODOLOGY: ACTG 5102 enrolled 47 HIV-1-infected subjects on stable ART, with <200 HIV RNA copies/mL and CD4 cell count >or=500 cells/microL. Subjects were randomly assigned to continue ART for 18 weeks with or without 3 cycles of interleukin-2 (IL-2) (cycle = 4.5 million IU sc BID x 5 days every 8 weeks). After 18 weeks ART was discontinued in all subjects until the CD4 cell count dropped below 350 cells/microL. Glucose and lipid parameters were evaluated every 8 weeks initially and at weeks 2, 4, 8 and every 8 weeks after TI. Immune activation was evaluated by flow-cytometry and soluble TNFR2 levels. PRINCIPAL
findingsBy week 8 of TI, levels of total cholesterol (TC) (median (Q1, Q3) (-0.73 (-1.19, -0.18) mmol/L, p<0.0001), LDL, HDL cholesterol (-0.36(-0.73,-0.03)mmol/L, p = 0.0007 and -0.05(-0.26,0.03), p = 0.0033, respectively) and triglycerides decreased (-0.40 (-0.84, 0.07) mmol/L, p = 0.005). However the TC/HDL ratio remained unchanged (-0.09 (-1.2, 0.5), p = 0.2). Glucose and insulin levels did not change (p = 0.6 and 0.8, respectively). After TI there was marked increase in immune activation (CD8+/HLA-DR+/CD38+ cells, 34% (13, 43), p<0.0001) and soluble TNFR2 (1089 ng/L (-189, 1655), p = 0.0008) coinciding with the rebound of HIV viremia.
conclusionsOur data suggests that interrupting antiretroviral therapy does not reduce cardiovascular disease (CVD) risk, as the improvements in lipid parameters are modest and overshadowed by the decreased HDL levels. Increased immune cell activation and systemic inflammatory responses associated with recrudescent HIV viremia may provide a more cogent explanation for the increased cardiovascular risk associated with treatment interruption and HIV infection.
trial registrationClinicalTrials.gov NCT00015704.
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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.