Background: Human immunodeficiency virus (HIV)-infected children often suffer from impaired growth. Highly active antiretroviral therapy (HAART) successfully reduces HIV 1 (HIV-1) RNA to 400 copies/mL or less in many children.
Objectives: To determine if age- and sex-adjusted growth z scores correlate with HIV-1 RNA level and if control of viral load for 48 and 96 weeks results in improved growth in children receiving highly active antiretroviral therapy.
Design: Secondary analysis of the cohort of children receiving ritonavir nested in a randomized, open-label, clinical trial.
Subjects And Methods: The Pediatric AIDS Clinical Trials Group Protocol 338 enrolled clinically stable, antiretroviral therapy-experienced, HIV-infected subjects aged 2 through 17 years. Using data from subjects randomized to ritonavir-containing regimens (n = 197), the association of growth z scores and HIV-1 RNA levels were examined.
Main Outcome Measures: Age- and sex-adjusted weight and height z scores.
Results: Enrollment weights were comparable with age- and sex-adjusted norms, but subjects receiving ritonavir-containing antiretroviral therapy were significantly shorter (mean z score, -0.57 [29th percentile]; 95% confidence interval, -0.73 to -0.40). Higher HIV-1 RNA levels correlated with lower growth z scores (P<.01). Subjects achieving and maintaining HIV-1 RNA of 400 copies/mL or less through 48 and 96 weeks experienced worse growth than subjects with a less controlled viral load.
Conclusions: In this pediatric cohort, a significant decline in height and weight z scores was found despite control of viral replication. Further studies of growth are necessary to assess if nutritional and hormonal adjuvants to highly active antiretroviral therapy should be considered to improve growth in HIV-infected children.
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http://dx.doi.org/10.1001/archpedi.156.5.497 | DOI Listing |
J Glob Antimicrob Resist
January 2025
Faculty of Medicine, Department of Microbiology, University of Tartu, Tartu, Estonia.
Objectives: We investigated the prevalence of drug resistance mutations (DRMs) in individuals newly diagnosed with HIV-1 in Estonia in 2020 and 2022, and in Ukrainian war refugees living with HIV who arrived in Estonia in 2022.
Methods: HIV-1 genomic RNA was sequenced in protease-reverse transcriptase and integrase regions. DRMs were determined separately by Stanford University CPR Tool and HIVdb Program.
Viruses
January 2025
Department of Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at transcription sites, may interact with host transcription factors, and display biophysical properties characteristic of biomolecular condensates. In the present work, we utilized a controlled in vitro condensate assay and advanced imaging approaches to investigate the effects of interactions between RSV Gag condensates and viral and nonviral RNAs on condensate abundance and organization.
View Article and Find Full Text PDFViruses
December 2024
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Treatment options for viral infections are limited and viruses have proven adept at evolving resistance to many existing therapies, highlighting a significant vulnerability in our defenses. In response to this challenge, we explored the modulation of cellular RNA metabolic processes as an alternative paradigm to antiviral development. Previously, the small molecule 5342191 was identified as a potent inhibitor of HIV-1 replication by altering viral RNA accumulation at doses that minimally affect host gene expression.
View Article and Find Full Text PDFViruses
December 2024
Laboratory of Molecular and Cellular Virology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
RNA-binding proteins (RBPs) are cellular factors involved in every step of RNA metabolism. During HIV-1 infection, these proteins are key players in the fine-tuning of viral and host cellular and molecular pathways, including (but not limited to) viral entry, transcription, splicing, RNA modification, translation, decay, assembly, and packaging, as well as the modulation of the antiviral response. Targeted studies have been of paramount importance in identifying and understanding the role of RNA-binding proteins that bind to HIV-1 RNAs.
View Article and Find Full Text PDFTrop Med Infect Dis
January 2025
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
HIV remains a significant health issue, especially in sub-Saharan Africa. There are 39 million people living with HIV (PLWH) globally. Treatment with ART improves patient outcomes by suppressing the HIV RNA viral load.
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