Background: The PIVOT trial examined whether patients with suppressed viral load on combination antiretroviral therapy could be safely switched long-term to ritonavir-boosted protease inhibitor (PI) monotherapy. The main trial publication reported that only one of 296 patients allocated to PI monotherapy experienced a loss of drug options due to protease mutations (identified by local Sanger sequencing resistance tests) likely selected by study drug.
Objectives: To assess if we had missed low frequency mutations, using a more sensitive methodology.
Study Design: We performed next generation sequencing (NGS) on all available frozen plasma samples with VL >1000 copies/ml from patients who were randomised to PI monotherapy. Assays were performed at Public Health England laboratories using a previously described method. Median coverage depth was 76,000 and the threshold for detection of minority variants was 2%. Drug susceptibility was predicted using the Stanford HIVdb algorithm.
Results: 17 of 26 potential samples, all from different patients, were identified and successfully tested. The median viral load was 6780 copies/ml and the median time since randomisation was 43 weeks. NGS revealed previously unidentified minority variant protease mutations (G73D, I54T, L89V) in three samples, at frequencies ranging between 2% and 10%. None of these mutations predicted intermediate or high level resistance, the trial primary outcome.
Discussion: This report adds to the body of evidence that ritonavir-boosted PI monotherapy, when used as a switch strategy with prompt detection of viral load rebound and early re-introduction of combination therapy, rarely leads to the development of clinically important protease resistance mutations.
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http://dx.doi.org/10.1016/j.jcv.2018.02.003 | DOI Listing |
Eur J Case Rep Intern Med
December 2024
Department of Internal Medicine, Hospital de Santa Maria, ULS de Santa Maria, Lisbon, Portugal.
Unlabelled: Cytomegalovirus (CMV) is a human herpes virus with a worldwide seroprevalence of 60-100%, mainly known to cause severe life-threatening disease in immunocompromised patients. In immunocompetent hosts (IMCh), CMV causes a self-limiting mononucleosis-like infection, and severe pictures are less recognized. We report a case of a previously healthy 62-year-old woman evaluated in the Internal Medicine outpatient clinic for 3 weeks of progressive fatigue, generalised inflammatory arthralgias, hypogastric discomfort and daily persistent fever.
View Article and Find Full Text PDFJ Family Med Prim Care
December 2024
Department of HIV and Blood Borne Viruses, Milton Keynes University Hospital, NHS Foundation Trust, Milton Keynes, UK.
We report a case of a 49-year-old female with a history of HIV infection for 12 years. The patient had excellent compliance with antiretroviral medications, raltegravir 400 mg twice daily and truvada once daily for HIV. Over the years, she maintained an undetectable viral load with a CD4+ count >200 cells/μL.
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January 2025
Department of Infectious Diseases, Nanning Center for Disease Control and Prevention, Nanning, 530023, China.
Introduction: COVID-19 has caused tremendous hardships and challenges around the globe. Due to the prevalence of asymptomatic and pre-symptomatic carriers, relying solely on disease testing to screen for infections is not entirely reliable, which may affect the accuracy of predictions about the pandemic trends. This study is dedicated to developing a predictive model aimed at estimating of the dynamics of COVID-19 at an early stage based on wastewater data, to assist in establishing an effective early warning system for disease control.
View Article and Find Full Text PDFAIDS Behav
January 2025
Department of Medicine, University of Alabama at Birmingham, 845 19th Street South, Bevill Biomedical Research Building, Room 256D, Birmingham, AL, 35294-2170, USA.
Antiretroviral therapy (ART) use and HIV suppression among people living with HIV (PLHIV) are critical for HIV control and prevention. Extreme restrictions on movement early during the COVID-19 pandemic in Uganda may have impeded the ability to initiate and sustain access to and use of ART. From our stepped-wedge cluster-randomized trial of an integrated PrEP and ART intervention for HIV-serodifferent couples at 12 ART clinics in Uganda, we identified participants who enrolled and had a 6-month post-ART initiation viral load measured before the beginning of the first COVID-19 lockdown (Period 1), participants whose enrollment and 6-month viral load measurement straddled pre-COVID and COVID lockdown times (Period 2), and participants whose enrollment and 6-month viral load were quantified entirely during COVID-19 (Period 3).
View Article and Find Full Text PDFCell Immunol
January 2025
Educational and Scientific Centre "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, 2, Hlushkov Avenue, Kyiv 03022, Ukraine.
Bacteriophage-derived dsRNA (bp-dsRNA), also known as Larifan, is a poly-functional and wide-spectrum antiviral medication with potent interferonogenic activity. In the lungs of golden Syrian hamsters infected with SARS-CoV-2, Larifan substantially reduces viral load and decreases infection-induced pathological lesion severity. Alveolar macrophages (AM) are key sentinel cells in the lung, which play an important role in antiviral innate immune responses and, at the same time, can trigger infection-associated hyper-inflammatory response.
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