Maintaining efficacy of human immunodeficiency virus (HIV) medications is challenging among children because of dosing difficulties, the limited number of approved drugs, and low rates of medication adherence. Drug level feedback (DLF) can support dose optimization and timely interventions to prevent treatment failure, but current tests are heavily instrumented and centralized. We developed the REverse-transcriptase ACTivity-crispR (REACTR) assay for rapid measurement of HIV drugs based on the extent of DNA synthesis by HIV reverse transcriptase. CRISPR-Cas enzymes bind to synthesized DNA, triggering collateral cleavage of quenched reporters and generating fluorescence. We measured azidothymidine triphosphate (AZT-TP), a key drug in pediatric HIV treatment, and investigated the impact of assay time and DNA template length on REACTR's sensitivity. REACTR selectively measured clinically relevant AZT-TP concentrations in the presence of genomic DNA and peripheral blood mononuclear cell lysate. REACTR has the potential to enable rapid point-of-care HIV DLF to improve pediatric HIV care.
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http://dx.doi.org/10.1101/2024.11.25.625292 | DOI Listing |
Pediatr Infect Dis J
December 2024
Pediatric Infectious Diseases Unit, Pediatric Department, Gregorio Marañón University Hospital, Madrid, Spain; Universidad Complutense de Madrid. UDIMIFFA (Gregorio Marañón Health Research Institute); PLANTAIDS network; CYTED program; CIBERFINFEC (Carlos III Health Institute).
We conducted a retrospective study to assess the effect of the COVID-19 pandemic on children living with HIV in Guatemala. A reduction in physical consultations and laboratory tests was observed in prepandemic versus pandemic period. However, immunovirological status of the children showed no differences.
View Article and Find Full Text PDFJ Int Assoc Provid AIDS Care
December 2024
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé, Cameroon.
Introduction: In low-and-middle-income-countries (LMIC), viral suppression is defined as plasma viral load (PVL) below 1000 copies/mL (low-level viremia [LLV]) and threshold for HIV drug resistance (HIVDR) testing. However, there is evidence that drug resistance mutations (DRMs) may emerge at LLV, thus compromising antiretroviral treatment (ART) response We evaluated sequencing success rates (SSR) at LLV, described HIVDR profiles and adequacy with potential efficacy of tenofovir-lamivudine-dolutegravir (TLD).
Methods: A cross-sectional study was conducted among individuals with LLV at the Chantal BIYA International Reference Centre, Yaoundé, Cameroon from January 2020 through August 2021.
Lancet Microbe
December 2024
Amsterdam University Medical Centres, Amsterdam, Netherlands; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands.
Background: Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.
View Article and Find Full Text PDFBMC Pregnancy Childbirth
December 2024
Department of Paediatrics & Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Background: Adverse birth outcomes (preterm birth, low birth weight, small for gestational age, and stillbirth) seem to persist in infants born to people with HIV, even in the context of maternal antiretroviral therapy. However, findings have been disparate, inconclusive, and difficult to compare directly across settings, partly owing to variable outcome definitions. We aimed to collate, compare, and map existing adverse birth outcome definitions to inform a harmonized approach to universally measure these outcomes in studies including pregnant people with HIV.
View Article and Find Full Text PDFMol Cell
December 2024
Drukier Institute for Children's Health, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. Electronic address:
The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality.
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