Publications by authors named "SHAFER R"

Introduction: COVID-19 vaccinations reduce the severity and number of symptoms for acute SARS-CoV-2 infections and may reduce the risk of developing Long COVID, also known as post-acute sequelae of SARS-CoV-2 (PASC). Limited and heterogenous data exist on how these vaccinations received after COVID-19 infection might impact the symptoms and trajectory of PASC, once persistent symptoms have developed.

Methods: We investigated the association of post-COVID-19 vaccination with any SARS-CoV-2 vaccine(s) on PASC symptoms in two independent cohorts: a retrospective chart review of self-reported data from patients ( = 128) with PASC seen in the Stanford PASC Clinic between May 2021 and May 2022 and a 2023 multinational survey assessment of individuals with PASC ( = 484).

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Treatment of obesity is a public health priority. However, little training in obesity medicine is currently integrated into residency programs. We integrated a 12-month obesity medicine training experience within a New York internal medicine residency program.

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Introduction: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV).

Methods: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI.

Results: Among the 395 PLWH receiving RPV, 180 (45.

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Article Synopsis
  • * It includes recommendations for using the anti-SARS-CoV-2 neutralizing antibody pemivibart as pre-exposure prophylaxis based on systematic review evidence.
  • * The guidelines follow GRADE methodology for assessing evidence certainty and strength of recommendations, and pemivibart is included in the FDA's Emergency Use Authorization.
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Importance: Previous studies have identified mutations in SARS-CoV-2 strains that confer resistance to nirmatrelvir, yet how often this resistance arises and its association with posttreatment virologic rebound is not well understood.

Objective: To examine the prevalence of emergent antiviral resistance after nirmatrelvir treatment and its association with virologic rebound.

Design, Setting, And Participants: This cohort study enrolled outpatient adults with acute COVID-19 infection from May 2021 to October 2023.

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  • The study examines how autistic individuals differ from neurotypical controls in terms of sustained fine motor control, focusing on the roles of visual feedback and motor memory.
  • Fifty-four autistic participants and 31 neurotypical controls aged 10-25 performed tests involving force sensors to measure their precision grip under visual and memory-guided conditions.
  • Results revealed that younger autistic individuals had less force accuracy and more variability during motor tasks compared to controls, but these differences seemed to level out as they reached adolescence.
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Background: In vitro passage experiments are crucial to the development of antiretroviral (ARV) drugs.

Methods: We created an online database containing data from 102 published studies in which HIV-1 or HIV-2 was cultured with increasing concentrations of the FDA-approved nucleoside RT inhibitors (NRTIs), nonnucleoside RT inhibitors (NNRTIs), integrase strand transfer inhibitors (INSTIs), protease inhibitors (PIs), capsid inhibitor (CAI) lenacapavir, and nucleoside RT translocation inhibitor (NRTTI) islatravir. We summarized the mutations selected in the subset of passage experiments with NRTIs lamivudine (3TC), emtricitabine (FTC), abacavir (ABC), tenofovir (TFV), and zidovudine (AZT), NNRTIs doravirine (DOR), efavirenz (EFV), and rilpivirine (RPV), INSTIs bictegravir (BIC), cabotegravir (CAB), and dolutegravir (DTG), and PIs atazanavir (ATV), darunavir (DRV), and lopinavir (LPV).

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Background: Large language models (LLMs) that can efficiently screen and identify studies meeting specific criteria would streamline literature reviews. Additionally, those capable of extracting data from publications would enhance knowledge discovery by reducing the burden on human reviewers.

Methods: We created an automated pipeline utilizing OpenAI GPT-4 32 K API version "2023-05-15" to evaluate the accuracy of the LLM GPT-4 responses to queries about published papers on HIV drug resistance (HIVDR) with and without an instruction sheet.

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Article Synopsis
  • A clinical trial was conducted at Stanford University to test the effectiveness of a 15-day treatment with nirmatrelvir-ritonavir for Post-Acute Sequelae of SARS-CoV-2 infection (PASC) in adults who have experienced moderate to severe symptoms for over 3 months.!* -
  • The study involved 155 participants who were randomly assigned to receive either the treatment or a placebo, with the main focus on measuring the severity of six key PASC symptoms after 10 weeks.!* -
  • Results indicated no significant improvement in symptom severity between the treatment and placebo groups, suggesting that nirmatrelvir-ritonavir may not effectively alleviate PASC symptoms in the tested population.!*
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Antimicrobial resistance poses a significant threat to the sustainability of effective treatments against the three most prevalent infectious diseases: malaria, human immunodeficiency virus (HIV) infection and tuberculosis. Therefore, there is an urgent need to develop novel drugs and treatment protocols capable of reducing the emergence of resistance and combating it when it does occur. In this Review, we present an overview of the status and underlying molecular mechanisms of drug resistance in these three diseases.

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  • Dolutegravir (DTG) is a highly effective medication in HIV treatment, but there's limited data on the risk of drug-resistance mutations arising in patients taking it.
  • A review of 2131 studies showed that in various patient scenarios, the prevalence of drug-resistance mutations was generally low, particularly in trials involving experienced patients or those on monotherapy.
  • To better understand drug-resistance risks, more innovative methods need to be applied in real-world studies, as trial data may not fully represent broader patient experiences.
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Background: Conversational agents (CA's) have shown promise in increasing accessibility to mental health resources. This study aimed to identify common themes of messages sent to a mental health CA (Wysa) related to ASD by general users and users that identify as having ASD.

Methods: This study utilized retrospective data.

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Autism spectrum disorder (ASD) is associated with a diverse range of etiological processes, including both genetic and non-genetic causes. For a plurality of individuals with ASD, it is likely that the primary causes involve multiple common inherited variants that individually account for only small levels of variation in phenotypic outcomes. This genetic landscape creates a major challenge for detecting small but important pathogenic effects associated with ASD.

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The global prevalence of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) stands at approximately 43 % among individuals who have previously had acute COVID-19. In contrast, in the United States, the National Center for Health Statistics (NCHS) estimates that around 11 % of individuals who have been infected with SARS-CoV-2 go on to experience long COVID. The underlying causes of PASC remains under investigation, and there are no currently established FDA-approved therapies.

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Article Synopsis
  • - The study investigates how HIV-1 reverse transcriptase (RT) initiation is influenced by the interaction between viral RNA and host tRNA, focusing on viruses that develop resistance to RT-inhibitors, specifically the M184V mutation and other resistance types.
  • - Sequencing of the 5'-leader RNA from individuals with various treatment statuses revealed significant variants and mixtures at specific positions, particularly positions 200 and 201, with higher mutation frequencies associated with M184V and NNRTI-resistance groups compared to untreated controls.
  • - Although no definitive co-evolution of RT and 5'-leader sequences was established, the discovery of a novel phenomenon at positions 200 and 201 warrants further investigation into the frequency of mutations
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: Dolutegravir (DTG)-based antiretroviral therapy (ART) rarely leads to virological failure (VF) and drug resistance in integrase strand transfer inhibitor (INSTI)-naïve persons living with HIV (PLWH). As a result, limited data are available on INSTI-associated drug resistance mutations (DRMs) selected by DTG-containing ART regimens. We reviewed studies published through July 2023 to identify those reporting emergent major INSTI-associated DRMs in INSTI-naïve PLWH receiving DTG and those containing in vitro DTG susceptibility results using a standardized assay.

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 • Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens.  • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens.  • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines.

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HIV drug resistance (HIVDR) is a major challenge to the effectiveness of antiretroviral therapy. Global efforts in addressing HIVDR require clear, transparent, and replicable reporting in HIVDR studies. We describe the rationale and recommended use of a checklist that should be included in reports of HIVDR incidence and prevalence.

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Background: HIV-1 RT initiation depends on interaction between viral 5'-leader RNA, RT, and host tRNA3. We therefore sought to identify co-evolutionary changes between the 5'-leader and RT in viruses developing RT-inhibitor resistance mutations.

Methods: We sequenced 5'-leader positions 37-356 of paired plasma virus samples from 29 individuals developing the NRTI-resistance mutation M184V, 19 developing an NNRTI-resistance mutation, and 32 untreated controls.

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Article Synopsis
  • A new HIV-1 capsid inhibitor, lenacapavir, necessitates the sequencing of capsid proteins in patients who have experienced this treatment to monitor viral presence.
  • The study analyzed capsid sequences from over 21,000 HIV-1 individuals to assess amino acid variation, focusing on how these variations relate to virus subtype and immune system pressure.
  • Results show that a majority of capsid positions have either no or only minor mutations, and understanding these variations is crucial for effective sequence interpretation and identifying potential new mutations linked to lenacapavir treatment.
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Background: The global prevalence of PASC is estimated to be present in 0·43 and based on the WHO estimation of 470 million worldwide COVID-19 infections, corresponds to around 200 million people experiencing long COVID symptoms. Despite this, its clinical features are not well-defined.

Methods: We collected retrospective data from 140 patients with PASC in a post-COVID-19 clinic on demographics, risk factors, illness severity (graded as one-mild to five-severe), functional status, and 29 symptoms and principal component symptoms cluster analysis.

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  • Doravirine shows a unique resistance profile, and this study investigates its effectiveness against drug-resistant HIV strains in ART-naïve individuals, particularly focusing on transmitted drug resistance (TDR).
  • The research analyzed doravirine susceptibility data from 42,535 HIV sequences collected between 2017 and 2021, identifying key mutations that impact doravirine's effectiveness, such as V106A and Y188L.
  • Findings reveal that while certain mutations significantly reduce doravirine susceptibility, most ART-naïve samples had lower susceptibility reductions, indicating doravirine may still be useful even in cases with some drug resistance.
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Background: Molecular epidemiological approaches provide opportunities to characterize HIV transmission dynamics. We analyzed HIV sequences and virus load (VL) results obtained during routine clinical care, and individual’s zip-code location to determine utility of this approach. Methods: HIV-1 pol sequences aligned using ClustalW were subtyped using REGA.

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  • The study evaluates the potential health benefits and risks of introducing long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) for HIV prevention in sub-Saharan Africa, considering concerns about the emergence of integrase-inhibitor resistance in treatment programs.
  • The researchers used a comprehensive HIV model to simulate various scenarios over 50 years, comparing outcomes with and without the introduction of cabotegravir-PrEP, targeting individuals at risk of developing drug resistance.
  • Cost-effectiveness analysis suggests that cabotegravir-PrEP could be comparable in price to current oral PrEP options, with the potential to significantly reduce HIV transmission while carefully monitoring the risk of resistance.
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