159 results on '"Jordan MR"'
Search Results
2. A MACHINE LEARNING CLASSIFICATION APPROACH TO PREDICT RADIOTHERAPEUTIC TOXICITY
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Jordan, Mr Karl, primary, Kelleher, John D., additional, and Meade, Aidan D., additional
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- 2022
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- View/download PDF
3. Low-Abundance Drug-Resistant HIV-1 Variants in Antiretroviral Drug-Naive Individuals: A Systematic Review of Detection Methods, Prevalence, and Clinical Impact
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Mbunkah, HA, Bertagnolio, S, Hamers, RL, Hunt, G, Inzaule, S, Rinke De Wit, TF, Paredes, R, Parkin, NT, Jordan, MR, Metzner, KJ, and WHO HIVResNet Working Grp
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minority variants ,antiretroviral therapy ,HIV-1 ,low-abundance drug-resistant HIV-1 variants ,next-generation sequencing ,antitretroviral drug-naive individuals ,HIV-1 drug resistance - Abstract
Background. The presence of high-abundance drug-resistant HIV-1 jeopardizes success of antiretroviral therapy (ART). Despite numerous investigations, the clinical impact of low-abundance drug-resistant HIV-1 variants (LA-DRVs) at levels
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- 2020
4. 274 - AN ANALYTICAL APPROACH TO MONITORING CLINICAL PATIENT SET-UP TOLERANCES IN SURFACE GUIDED RADIOTHERAPY (SGRT)
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Griffin, Mr John, Kelly, Michael, and Jordan, Mr Karl
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- 2022
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- View/download PDF
5. 232 - A MACHINE LEARNING CLASSIFICATION APPROACH TO PREDICT RADIOTHERAPEUTIC TOXICITY
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Jordan, Mr Karl, Kelleher, John D., and Meade, Aidan D.
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- 2022
- Full Text
- View/download PDF
6. Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study
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Phillips, AN, Cambiano, V, Nakagawa, F, Revill, P, Jordan, MR, Hallett, TB, Doherty, M, Luca, A, Lundgren, JD, Mhangara, M, Apollo, T, Mellors, J, Nichols, B, Parikh, U, Pillay, D, de Wit, TR, Sigaloff, K, Havlir, D, Kuritzkes, DR, Pozniak, A, van de Vijver, David, Vitoria, M, Wainberg, MA, Raizes, E, Bertagnolio, S, Phillips, AN, Cambiano, V, Nakagawa, F, Revill, P, Jordan, MR, Hallett, TB, Doherty, M, Luca, A, Lundgren, JD, Mhangara, M, Apollo, T, Mellors, J, Nichols, B, Parikh, U, Pillay, D, de Wit, TR, Sigaloff, K, Havlir, D, Kuritzkes, DR, Pozniak, A, van de Vijver, David, Vitoria, M, Wainberg, MA, Raizes, E, and Bertagnolio, S
- Published
- 2018
7. High Levels of Transmitted HIV Drug Resistance in a Study in Papua New Guinea
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Menéndez-Arias, L, Lavu, E, Kave, E, Mosoro, E, Markby, J, Aleksic, E, Gare, J, Elsum, IA, Nano, G, Kaima, P, Dala, N, Gurung, A, Bertagnolio, S, Crowe, SM, Myatt, M, Hearps, AC, Jordan, MR, Menéndez-Arias, L, Lavu, E, Kave, E, Mosoro, E, Markby, J, Aleksic, E, Gare, J, Elsum, IA, Nano, G, Kaima, P, Dala, N, Gurung, A, Bertagnolio, S, Crowe, SM, Myatt, M, Hearps, AC, and Jordan, MR
- Abstract
INTRODUCTION: Papua New Guinea is a Pacific Island nation of 7.3 million people with an estimated HIV prevalence of 0.8%. ART initiation and monitoring are guided by clinical staging and CD4 cell counts, when available. Little is known about levels of transmitted HIV drug resistance in recently infected individuals in Papua New Guinea. METHODS: Surveillance of transmitted HIV drug resistance in a total of 123 individuals recently infected with HIV and aged less than 30 years was implemented in Port Moresby (n = 62) and Mount Hagen (n = 61) during the period May 2013-April 2014. HIV drug resistance testing was performed using dried blood spots. Transmitted HIV drug resistance was defined by the presence of one or more drug resistance mutations as defined by the World Health Organization surveillance drug resistance mutations list. RESULTS: The prevalence of non-nucleoside reverse transcriptase inhibitor transmitted HIV drug resistance was 16.1% (95% CI 8.8%-27.4%) and 8.2% (95% CI 3.2%-18.2%) in Port Moresby and Mount Hagen, respectively. The prevalence of nucleoside reverse transcriptase inhibitor transmitted HIV drug resistance was 3.2% (95% CI 0.2%-11.7%) and 3.3% (95% CI 0.2%-11.8%) in Port Moresby and Mount Hagen, respectively. No protease inhibitor transmitted HIV drug resistance was observed. CONCLUSIONS: The level of non-nucleoside reverse transcriptase inhibitor drug resistance in antiretroviral drug naïve individuals recently infected with HIV in Port Moresby is amongst the highest reported globally. This alarming level of transmitted HIV drug resistance in a young sexually active population threatens to limit the on-going effective use of NNRTIs as a component of first-line ART in Papua New Guinea. To support the choice of nationally recommended first-line antiretroviral therapy, representative surveillance of HIV drug resistance among antiretroviral therapy initiators in Papua New Guinea should be urgently implemented.
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- 2017
8. Targets for intervention to improve virological outcomes for patients receiving free antiretroviral therapy in Tamil Nadu, India
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McMahon, JH, Manoharan, A, Wanke, C, Mammen, S, Jose, H, Malini, T, Kadavanu, T, Jordan, MR, Elliott, JH, Lewin, SR, Mathai, D, McMahon, JH, Manoharan, A, Wanke, C, Mammen, S, Jose, H, Malini, T, Kadavanu, T, Jordan, MR, Elliott, JH, Lewin, SR, and Mathai, D
- Abstract
Operational research to identify factors predicting poor clinical outcomes is critical to maximize patient care and prolong first-line regimens for those receiving free antiretroviral therapy (ART) in India. We sought to identify social or clinical factors amenable to intervention that predict virological outcomes after 12 months of ART. We examined a retrospective cohort of consecutive adults initiating free nonnucleoside reverse transcriptase inhibitor-based regimens. Individuals remaining in care 12 months post-ART initiation were tested for HIV viral load and surveyed to identify barriers and facilitators to adherence, and to determine clinic travel times and associated costs. Uni- and multivariate logistic regression identified factors predicting HIV viral load >200 copies/mL after 12 months of ART. Of 230 adults initiating ART, 10% of patients died, 8% transferred out, 5% were lost to follow-up, and 174/230 (76%) completed 12 months of ART, the questionnaire, and viral load testing. HIV viral load was <200 copies/mL in 140/174 (80%) patients. In multivariate models, being busy with work or caring for others (OR 2.9, p < 0.01), having clinic transport times ≥ 3 hours (OR 3.0, p = 0.02), and alcohol use (OR 4.8, p = 0.03) predicted viral load >200 copies/mL after 12 months of ART. Clinical outcomes following ART are related to programmatic factors such as prolonged travel time and individual factors such as being busy with family or using alcohol. Simple interventions that alter these factors should be evaluated to improve clinical outcomes for populations receiving free ART in similar settings.
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- 2014
9. Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: a mathematical modelling study
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Nichols, Brooke, Sigaloff, KCE, Kityo, C, Hamers, RL, Baltussen, RMPM, Bertagnolio, S, Jordan, MR, Hallett, TB, Boucher, Charles, de Wit, TFR, van de Vijver, David, Nichols, Brooke, Sigaloff, KCE, Kityo, C, Hamers, RL, Baltussen, RMPM, Bertagnolio, S, Jordan, MR, Hallett, TB, Boucher, Charles, de Wit, TFR, and van de Vijver, David
- Abstract
Introduction: Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. Methods: We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50-90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda. Results: The prevalence of TDR is predicted to rise from 6.7% (interquartile range [IQR] 6.2-7.2%) in 2014, to 6.8% (IQR 6.1-7.6%), 10.0% (IQR 8.9-11.5%) and 11.1% (IQR 9.7-13.0%) in 2024 if treatment is initiated at a CD4 <350, <500, or immediately, respectively. The absolute number of TDR cases is predicted to decrease 4.4-8.1% when treating earlier compared to treating at CD4 <350 due to the preventative effects of earlier treatment. Most cases of TDR can be averted by increasing second-line treatment (additional 7.1-10.2% reduction), followed by increased viral load monitoring (<2.7%) and pre-therapy genotyping (<1.0%). Only increasing second-line treatment is cost-effective, ranging from $1612 to $2234 (IQR $450-dominated) per QALY gained. Conclusions: While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patien
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- 2014
10. Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: modelling study and economic analysis
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Phillips, An, Cambiano, V, Miners, A, Revill, P, Pillay, D, Lundgren, Jd, Bennett, D, Raizes, E, Nakagawa, F, De Luca, Andrea, Vitoria, M, Barcarolo, J, Perriens, J, Jordan, Mr, Bertagnolio, S., De Luca, Andrea (ORCID:0000-0002-8311-6935), Phillips, An, Cambiano, V, Miners, A, Revill, P, Pillay, D, Lundgren, Jd, Bennett, D, Raizes, E, Nakagawa, F, De Luca, Andrea, Vitoria, M, Barcarolo, J, Perriens, J, Jordan, Mr, Bertagnolio, S., and De Luca, Andrea (ORCID:0000-0002-8311-6935)
- Abstract
With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial levels of transmitted drug resistance.
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- 2014
11. Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam
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Jordan, MR, primary, Obeng-Aduasare, Y, additional, Sheehan, H, additional, Hong, SY, additional, Terrin, N, additional, Duong, DV, additional, Trung, NV, additional, Wanke, C, additional, Kinh, NV, additional, and Tang, AM, additional
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- 2013
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12. Update on World Health Organization HIV drug resistance prevention and assessment strategy: 2004-2011
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Jordan, Mr, Bennett, De, Wainberg, Ma, Havlir, D, Hammer, S, Yang, C, Morris, L, Peeters, M, Wensing, Am, Parkin, N, Nachega, Jb, Phillips, A, De Luca, Andrea, Geng, E, Calmy, A, Raizes, E, Sandstrom, P, Archibald, Cp, Perriëns, J, Mcclure, Cm, Hong, Sy, Mcmahon, Jh, Dedes, N, Sutherland, D, Bertagnolio, S., De Luca, Andrea (ORCID:0000-0002-8311-6935), Jordan, Mr, Bennett, De, Wainberg, Ma, Havlir, D, Hammer, S, Yang, C, Morris, L, Peeters, M, Wensing, Am, Parkin, N, Nachega, Jb, Phillips, A, De Luca, Andrea, Geng, E, Calmy, A, Raizes, E, Sandstrom, P, Archibald, Cp, Perriëns, J, Mcclure, Cm, Hong, Sy, Mcmahon, Jh, Dedes, N, Sutherland, D, Bertagnolio, S., and De Luca, Andrea (ORCID:0000-0002-8311-6935)
- Abstract
The HIV drug resistance (HIVDR) prevention and assessment strategy, developed by the World Health Organization (WHO) in partnership with HIVResNet, includes monitoring of HIVDR early warning indicators, surveys to assess acquired and transmitted HIVDR, and development of an accredited HIVDR genotyping laboratory network to support survey implementation in resource-limited settings. As of June 2011, 52 countries had implemented at least 1 element of the strategy, and 27 laboratories had been accredited. As access to antiretrovirals expands under the WHO/Joint United Nations Programme on HIV/AIDS Treatment 2.0 initiative, it is essential to strengthen HIVDR surveillance efforts in the face of increasing concern about HIVDR emergence and transmission.
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- 2012
13. Determinants of HIV drug resistance and public health implications in low- and middle-income countries
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Bertagnolio, S, De Luca, Andrea, Vitoria, M, Essajee, S, Penazzato, M, Hong, Sy, Mcclure, C, Duncombe, C, Jordan, Mr, De Luca, Andrea (ORCID:0000-0002-8311-6935), Bertagnolio, S, De Luca, Andrea, Vitoria, M, Essajee, S, Penazzato, M, Hong, Sy, Mcclure, C, Duncombe, C, Jordan, Mr, and De Luca, Andrea (ORCID:0000-0002-8311-6935)
- Abstract
Global scale-up of antiretroviral therapy (ART) in low- and middle-income countries (LMICs) is an unprecedented public health achievement. With planned efforts of expanded ART access including earlier treatment initiation and the use of antiretroviral (ARV) drugs for prophylaxis, increasing levels of HIV drug resistance (HIVDR) are expected.Several factors may lead to selection and transmission of significant HIVDR in LMICs, which will lead to decreased population-level efficacy of standard first- and second-line ART regimens. These factors include low genetic barrier of some ARVs to resistance development, drug-drug interactions, inappropriate prescribing practices, interruption of drug supply, poor retention in care and lack of routine viral load monitoring.To maximize long-term effectiveness of available ARVs, policy makers and programme managers in LMICs should routinely monitor programme factors associated with emergence and transmission of HIVDR and implement routine HIVDR surveillance following standardized methods. When surveillance results suggest the need for action, specific public health interventions must be taken to adjust ART programme functioning to minimize further emergence and transmission of HIVDR.In this paper, we review ARV drug, HIV, patient and programme-related determinants of HIVDR. Additionally, we summarize the World Health Orgnization's global HIVDR surveillance and prevention strategy and describe resulting public health and policy implications.
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- 2012
14. Drug Resistance Mutations for Surveillance of Transmitted HIV-1 Drug-Resistance: 2009 Update
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Bennett, DE, Camacho, RJ, Otelea, D, Kuritzkes, DR, Fleury, H, Kiuchi, M, Heneine, W, Kantor, R, Jordan, MR, Schapiro, JM, Vandamme, AM, Sandstrom, P, Boucher, Charles, van de Vijver, David, Rhee, SY, Liu, TF, Pilay, D, Shafer, RW, Bennett, DE, Camacho, RJ, Otelea, D, Kuritzkes, DR, Fleury, H, Kiuchi, M, Heneine, W, Kantor, R, Jordan, MR, Schapiro, JM, Vandamme, AM, Sandstrom, P, Boucher, Charles, van de Vijver, David, Rhee, SY, Liu, TF, Pilay, D, and Shafer, RW
- Abstract
Programs that monitor local, national, and regional levels of transmitted HIV-1 drug resistance inform treatment guidelines and provide feedback on the success of HIV-1 treatment and prevention programs. To accurately compare transmitted drug resistance rates across geographic regions and times, the World Health Organization has recommended the adoption of a consensus genotypic definition of transmitted HIV-1 drug resistance. In January 2007, we outlined criteria for developing a list of mutations for drug-resistance surveillance and compiled a list of 80 RT and protease mutations meeting these criteria (surveillance drug resistance mutations; SDRMs). Since January 2007, several new drugs have been approved and several new drug-resistance mutations have been identified. In this paper, we follow the same procedures described previously to develop an updated list of SDRMs that are likely to be useful for ongoing and future studies of transmitted drug resistance. The updated SDRM list has 93 mutations including 34 NRTI-resistance mutations at 15 RT positions, 19 NNRTI-resistance mutations at 10 RT positions, and 40 PI-resistance mutations at 18 protease positions.
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- 2009
15. Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.
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Jordan, MR, Obeng-Aduasare, Y, Sheehan, H, Hong, SY, Terrin, N, Duong, DV, Trung, NV, Wanke, C, Kinh, NV, Tang, AM, Jordan, M R, Hong, S Y, Duong, D V, Trung, N V, Kinh, N V, and Tang, A M
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HIV infections ,INTRAVENOUS drug abusers ,ANTIRETROVIRAL agents ,SEX industry ,HIV infection epidemiology ,INTRAVENOUS drug abuse ,DRUGS ,LONGITUDINAL method ,PATIENT compliance ,VIRAL load ,SOCIOECONOMIC factors ,DRUG abusers ,HIGHLY active antiretroviral therapy ,TREATMENT effectiveness ,ANTI-HIV agents ,DISEASE complications - Abstract
The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9 ± 4.9 years. The median duration on antiretroviral therapy was 16.2 ± 12.7 months; 83% reported ‘very good’ or ‘perfect’ adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30–3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14–1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases. [ABSTRACT FROM PUBLISHER]
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- 2014
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16. Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.
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Jordan MR, La H, Nguyen HD, Sheehan H, Lien TT, Duong DV, Hellinger J, Wanke C, Tang AM, Jordan, M R, La, H, Nguyen, H D, Sheehan, H, Lien, T T M, Duong, D V, Hellinger, J, Wanke, C, and Tang, A M
- Abstract
Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programmes. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1-infected drug users receiving antiretroviral therapy (ART) for at least six months in Hanoi, Vietnam. The mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA <1000 copies/mL). Correlates of viral suppression include self-reported > or = 95% adherence (P < 0.01) and current use of trimethoprim/sulphamethoxazole (P < 0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (P = 0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlight the need for adherence promotion, risk reduction programmes, and population-based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited. [ABSTRACT FROM AUTHOR]
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- 2009
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17. Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.
- Author
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Inzaule S, Easterbrook P, Latona A, Ford NP, Irving W, Matthews PC, Vitoria M, Duncombe C, Giron A, McCluskey S, Lesi O, Tchamgoue S, Halford R, Adda D, Thomson E, Dusheiko G, and Jordan MR
- Abstract
Background: The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy., Methods: We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis., Results: The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors., Discussion: At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment., Competing Interests: Potential conflicts of interest. W. I. reports personal fees from Roche diagnostics, Gilead Sciences, and Source Bioscience Limited outside of the submitted work and stock or stock options in GlaxoSmithKline. P. C. M. reports funding from Francis Crick Institute and University College London Biomedical Research Centre (BRC) and Wellcome Trust during the submitted work, as well as royalties from Oxford University Press and funding from GlaxoSmithKline outside of the submitted work. S. T. reports funding or personal fees ViiV Healthcare and Gilead Sciences outside of the submitted work. D. A. reports funding from Gilead Sciences and Pfizer outside of the submitted work. R. H. serves as the president of World Hepatitis Alliance. All other authors declare no competing interests. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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18. The effect of replication protein A inhibition and post-translational modification on ATR kinase signaling.
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Jordan MR, Oakley GG, Mayo LD, Balakrishnan L, and Turchi JJ
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- Humans, Phosphorylation, DNA-Binding Proteins metabolism, Protein Binding, Carrier Proteins, Nuclear Proteins, Replication Protein A metabolism, Ataxia Telangiectasia Mutated Proteins metabolism, Signal Transduction, Protein Processing, Post-Translational, DNA, Single-Stranded metabolism
- Abstract
The ATR kinase responds to elevated levels of single-stranded DNA (ssDNA) to activate the G2/M checkpoint, regulate origin utilization, preserve fork stability, and allow DNA repair to ensure genome integrity. The intrinsic replication stress in cancer cells makes this pathway an attractive therapeutic target. The ssDNA that drives ATR signaling is sensed by the ssDNA-binding protein replication protein A (RPA), which acts as a platform for ATRIP recruitment and subsequent ATR activation by TopBP1. We have developed chemical RPA inhibitors (RPAi) that block RPA-ssDNA interactions (RPA-DBi) and RPA protein-protein interactions (RPA-PPIi); both activities are required for ATR activation. Here, we biochemically reconstitute the ATR kinase signaling pathway and demonstrate that RPA-DBi and RPA-PPIi abrogate ATR-dependent phosphorylation of target proteins with selectivity advantages over active site ATR inhibitors. We demonstrate that RPA post-translational modifications (PTMs) impact ATR kinase activation but do not alter sensitivity to RPAi. Specifically, phosphorylation of RPA32 and TopBP1 stimulate, while RPA70 acetylation does not affect ATR phosphorylation of target proteins. Collectively, this work reveals the RPAi mechanism of action to inhibit ATR signaling that can be regulated by RPA PTMs and offers insight into the anti-cancer activity of ATR pathway-targeted cancer therapeutics., (© 2024. The Author(s).)
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- 2024
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19. Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review.
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Chu C, Tao K, Kouamou V, Avalos A, Scott J, Grant PM, Rhee SY, McCluskey SM, Jordan MR, Morgan RL, and Shafer RW
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- Humans, Cross-Sectional Studies, Prevalence, Lamivudine therapeutic use, Heterocyclic Compounds, 3-Ring therapeutic use, Heterocyclic Compounds, 3-Ring pharmacology, Mutation, HIV Infections drug therapy, HIV Infections epidemiology, HIV Integrase Inhibitors therapeutic use, HIV Integrase Inhibitors pharmacology, Anti-HIV Agents therapeutic use, Oxazines, Piperazines, Pyridones
- Abstract
Background: Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART., Methods: We performed a PubMed search using the term "Dolutegravir", last updated 18 December 2023, to estimate the prevalence of VF with emergent INSTI DRMs in people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART., Results: Of 2131 retrieved records, 43 clinical trials, 39 cohorts, and 6 cross-sectional studies provided data across 6 clinical scenarios based on ART history, virological status, and co-administered ARVs: (1) ART-naïve PLWH receiving DTG plus two NRTIs; (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on a previous regimen receiving DTG plus two NRTIs; (4) ART-experienced PLWH with virological suppression receiving DTG plus two NRTIs; (5) ART-experienced PLWH with virological suppression receiving DTG and a second ARV; and (6) ART-experienced PLWH with virological suppression receiving DTG monotherapy. The median proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.5% for scenario 3 and 3.4% for scenario 6. In the remaining four trial scenarios, VF prevalence with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, whereas cross-sectional studies yielded prevalence data lacking denominator details., Conclusions: In clinical trials, the prevalence of VF with emergent INSTI DRMs in PLWH receiving DTG-containing regimens has been low. Novel approaches are required to assess VF prevalence with emergent INSTI DRMs in PLWH receiving DTG in real-world settings.
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- 2024
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20. Cardiac Rehabilitation Program Effect on Health-Related Quality of Life Among Patients With Coronary Artery Bypass Grafts.
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Alrahahleh M, Subih M, Megdadi R, Altarabsheh SE, Alfawaeer Z, Saad A, and Khalil T
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- Humans, Quality of Life, Coronary Artery Bypass, Life Style, Cardiac Rehabilitation
- Abstract
Coronary artery bypass graft (CABG) necessitates modification in patients' lifestyle after discharge, which leads to a decrease in their health-related quality of life (HRQOL). Hence, cardiac rehabilitation programs (CRPs) are needed. This study aimed to explore the effect of a CRP on HRQOL and physiological factors on CABG patients after discharge. The study used a quasiexperimental pre-/posttest design. Two experimental and control groups tested with 30 patients with CABG surgery participated in a rehabilitation center after discharge. The Arabic version of the Nottingham Health Profile for measuring HRQOL was used. In addition to several sociodemographic and physiological variables, findings indicated a significant improvement in HRQOL and its domains for the experimental group after CRP (mean = 2.06, SD = 1.7) when compared with the control group (mean = 19.9, SD = 3.1; P = .01), as well as some physiological variables 3 months after surgery. The CRP is an important intervention that administrators and cardiologists should take into consideration for CABG patients. It improves not just their HRQOL but also many physiological indicators., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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21. High viral suppression and detection of dolutegravir-resistance associated mutations in treatment-experienced Tanzanian adults living with HIV-1 in Dar es Salaam.
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Bwire GM, Aiko BG, Mosha IH, Kilapilo MS, Mangara A, Kazonda P, Swai JP, Swalehe O, Jordan MR, Vercauteren J, Sando D, Temba D, Shao A, Mauka W, Decouttere C, Vandaele N, Sangeda RZ, Killewo J, and Vandamme AM
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- Humans, Adult, Male, Female, Child, Tanzania, Cross-Sectional Studies, Drug Resistance, Viral genetics, Reverse Transcriptase Inhibitors pharmacology, Reverse Transcriptase Inhibitors therapeutic use, Mutation, Integrases genetics, Viral Load, HIV Infections, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, HIV-1 genetics, HIV Seropositivity drug therapy
- Abstract
To curb HIV infection rate in Tanzania, antiretroviral therapy (ART) has been scaled up since 2006, and in 2019, the country shifted to regimen including dolutegravir as a default first line. We assessed the success of ART and the contribution of HIV drug resistance (HIVDR) to unsuppressed viral loads. Between February and May 2023 a cross-sectional survey with random sampling was conducted in the six clinics in an urban cohort in Dar es Salaam. Patients with unsuppresed viral loads (local criteria viral load (VL) ≥ 1000 copies/mL) were tested for HIVDR mutations using the WHO adapted protocol for plasma samples. Mutations were interpreted using the Stanford HIVDR database. In total 600 individuals participated in this survey, the majority were female (76.83%), mean age ([Formula: see text] standard deviation) was 44.0 ([Formula: see text] 11.6) years. The median duration on ART (interquartile range) was 6.5 (3.9-10.2) years. Approximately 99% were receiving tenofovir + lamivudine + dolutegravir as a fixed dose combination. VL testing was successful in 99.67% (598/600) of survey patients and only 33 had VL ≥ 1000 copies/mL, resulting in a viral suppression level of 94.48% (565/598, 95% CI 92.34-96.17%). For 23 samples, protease and reverse transcriptase (RT) genotyping were successful, with 13 sequences containing RT inhibitor surveillance drug resistance mutations (SDRMs) (56.5%). No SDRM against protease inhibitors were detected. Thirty samples were successfully genotyped for integrase with 3 sequences (10.08%) containing integrase strand transfer inhibitor (INSTI) SDRMs. In samples successfully genotyped in the three genetic regions, 68.18% (16/22) had a genotypic susceptibility score (GSS) ≥ 2.5 for the concurrent regimen, implying factors beyond drug resistance caused the unsuppressed viral load. For five patients, GSS indicated that HIVDR may have caused the unsuppressed viral load. All three patients with INSTI resistance mutations were highly resistant to dolutegravir and accumulated nucleoside and non-nucleoside RT inhibitor HIVDR mutations. Although in this cohort the last 95 UNAIDS target was almost achieved, HIVDR mutations, including INSTIs resistance mutations were detected in HIV-positive individuals taking ART for at least one year. We recommend the design and implementation of high-impact interventions to prevent the increase of HIVDR, failure of dolutegravir and address the non-resistance factors in the study area., (© 2023. The Author(s).)
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- 2023
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22. First case report of a perinatally HIV-infected infant with HIV resistance to dolutegravir associated with tenofovir/lamivudine/dolutegravir use in mothers.
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Francois K, Van Onacker JD, Jordan MR, Journel I, Buteaue J, Pierre E, Duval N, Dos Santos G, Giron A, Geffrard H, Sued O, and Inzaule SC
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- Pregnancy, Infant, Female, Humans, Lamivudine therapeutic use, Tenofovir therapeutic use, Mothers, Heterocyclic Compounds, 3-Ring therapeutic use, Oxazines therapeutic use, HIV Infections complications, HIV Infections drug therapy, HIV Infections prevention & control, Anti-HIV Agents therapeutic use
- Abstract
Perinatally HIV-infected infants can be infected with a drug-resistant virus or select for drug resistance by exposure to sub-therapeutic levels of maternal antiretroviral drugs present in breastmilk or from sub-therapeutic infant prophylaxis. We report a case of dolutegravir resistance detected in a treatment-naive perinatally HIV-infected infant whose mother was receiving tenofovir/lamivudine/dolutegravir. This case was detected during a national survey of HIV drug resistance in Haiti amongst infants testing positive for HIV through the national early infant diagnosis program between April 2020 and March 2021. This unique case underscores the need for prompt management of high viral loads in pregnant and breastfeeding women and supports HIV drug resistance surveillance efforts targeted at antiretroviral therapy-naive infants born to mothers in low-and middle-income countries., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2023
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23. Checklist for studies of HIV drug resistance prevalence or incidence: rationale and recommended use.
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Mbuagbaw L, Garcia C, Brenner B, Cecchini D, Chakroun M, Djiadeu P, Holguin A, Mor O, Parkin N, Santoro MM, Ávila-Ríos S, Fokam J, Phillips A, Shafer RW, and Jordan MR
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- Humans, Checklist, Prevalence, Research Design, Drug Resistance, Viral, HIV, HIV Infections drug therapy, HIV Infections epidemiology
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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. After preliminary consultations with experts on HIVDR and establishing the need for guidance on HIVDR reporting, we used a sequential, explanatory, mixed methods approach to create the checklist; together with the accompanying articles, the checklist was reviewed by the authors and validated externally. The checklist for studies on HIVDR prevalence or incidence (CEDRIC-HIV) includes 15 recommended items that would enhance transparency and facilitate interpretation, comparability, and replicability of HIVDR studies. CEDRIC-HIV will help authors of HIVDR studies prepare research reports and assist reviewers and editors in assessments of completeness of reporting. The checklist will also facilitate statistical pooling and interpretation of HIVDR data., Competing Interests: Declaration of interests MMS declares receiving compensation from Theratechnologies, Janssen-Cilag, and ViiV Healthcare. RWS declares receiving compensation from Gilead Sciences, Vir Biotechnology, and GlaxoSmithKline. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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24. Recommendations on data sharing in HIV drug resistance research.
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Inzaule SC, Siedner MJ, Little SJ, Avila-Rios S, Ayitewala A, Bosch RJ, Calvez V, Ceccherini-Silberstein F, Charpentier C, Descamps D, Eshleman SH, Fokam J, Frenkel LM, Gupta RK, Ioannidis JPA, Kaleebu P, Kantor R, Kassaye SG, Kosakovsky Pond SL, Kouamou V, Kouyos RD, Kuritzkes DR, Lessells R, Marcelin AG, Mbuagbaw L, Minalga B, Ndembi N, Neher RA, Paredes R, Pillay D, Raizes EG, Rhee SY, Richman DD, Ruxrungtham K, Sabeti PC, Schapiro JM, Sirivichayakul S, Steegen K, Sugiura W, van Zyl GU, Vandamme AM, Wensing AMJ, Wertheim JO, Gunthard HF, Jordan MR, and Shafer RW
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- Humans, Phylogeny, Drug Resistance, Viral genetics, Anti-Retroviral Agents therapeutic use, Mutation, HIV Infections drug therapy, HIV Infections epidemiology, HIV-1 genetics, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use
- Abstract
• 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. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV., Competing Interests: SJL has received research funding paid to her institution from Gilead Sciences. VC has received travel grants, advisor honorarium and research grant from Merck Sharp & Dohme, ViiV Healthcare and Gilead Sciences. FCS has been a consultant to ViiV Healthcare, Gilead Sciences and Merck Sharp & Dohme, and received research grants paid to her institution from Gilead Sciences. CC has received honoraria and conference travels grants from Merck Sharp & Dohme, Gilead Sciences, and ViiV Healthcare. DD has received honoraria for participation in advisory boards and conference travel grants ViiV Healthcare, Gilead Sciences, Janssen Pharmaceuticals, and Merck Sharp & Dohme. LF has received NIH research grants paid to her institution. RKG has received honoraria for participation on advisory boards from Gilead-Sciences and GlaxoSmithKline. RDK has received research grants from Gilead Sciences paid to his institution. DRK is a consultant to and has received honoraria from AbbVie, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Merck, Roche, and ViiV Healthcare. DRK has also received honoraria from Gilead for expert testimony and speaking fees from Gilead Sciences and Janssen Pharmaceuticals and has received research support paid to his institution from Gilead Sciences, Merck, and ViiV Healthcare. AGM received travel grants, honoraria and study grants from Gilead Sciences, Merck Sharp & Dohme, ViiV Healthcare, GlaxoSmithKline, Roche, and Astra Zeneca. RP has received research grants paid to his institution from Merck Sharp & Dohme and ViiV Healthcare and consulting fees from Gilead Sciences, Merck Sharp & Dohme, GlaxoSmithKline, Atea Pharmaceuticals, Roche, and Shinogi Pharmaceuticals. PCS is a co-founder of, shareholder in, and consultant to Sherlock Biosciences and Delve Bio, and a board member of and shareholder in Danaher Corporation. JMS has received research support, honorarium, or consulting fees from the following: Abbvie, Merck, Gilead Sciences, GlaxoSmithKline, Tibotec-Janssen, Teva, Virology Education and ViiV Healthcare. He has received travel support and stipends for advisory work for the World Health Organization. WS has received speaking honoraria from GlaxoSmithKline, ViiV Healthcare, Merck Sharp & Dohme, Pfizer, and Abbott Pharmaceuticals. AMJW has received research support paid to her institution by Gilead Sciences and has consulted for Gilead Sciences and ViiV Healthcare. JOW receives funding from grants and contracts to his institution from NIH and CDC pertaining to work on HIV molecular epidemiology. HFG has received grants paid to his institution from Gilead Sciences, and Roche, and has received consulting fees from Merck, Gilead Sciences, ViiV Healthcare, Janssen Pharmaceuticals, GlaxoSmithKline, Johnson and Johnson, and Novartis. RWS has received honoraria for participation in advisory boards from Gilead Sciences and GlaxoSmithKline and speaking honoraria from Gilead Sciences and ViiV Healthcare., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
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- 2023
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25. Treatment Emergent Dolutegravir Resistance Mutations in Individuals Naïve to HIV-1 Integrase Inhibitors: A Rapid Scoping Review.
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Tao K, Rhee SY, Chu C, Avalos A, Ahluwalia AK, Gupta RK, Jordan MR, and Shafer RW
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- Humans, Heterocyclic Compounds, 3-Ring pharmacology, Heterocyclic Compounds, 3-Ring therapeutic use, Mutation, HIV Integrase Inhibitors pharmacology, HIV Integrase Inhibitors therapeutic use, HIV-1 genetics
- Abstract
Background : 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. Methods: 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. Results: We identified 36 publications reporting 99 PLWH in whom major nonpolymorphic INSTI-associated DRMs developed on a DTG-containing regimen and 21 publications containing 269 in vitro DTG susceptibility results. DTG-selected DRMs clustered into four largely non-overlapping mutational pathways characterized by mutations at four signature positions: R263K, G118R, N155H, and Q148H/R/K. Eighty-two (82.8%) viruses contained just one signature DRM, including R263K ( n = 40), G118R ( n = 24), N155H ( n = 9), and Q148H/R/K ( n = 9). Nine (9.1%) contained ≥1 signature DRM, and eight (8.1%) contained just other DRMs. R263K and G118R were negatively associated with one another and with N155H and Q148H/K/R. R263K alone conferred a median 2.0-fold (IQR: 1.8-2.2) reduction in DTG susceptibility. G118R alone conferred a median 18.8-fold (IQR:14.2-23.4) reduction in DTG susceptibility. N155H alone conferred a median 1.4-fold (IQR: 1.2-1.6) reduction in DTG susceptibility. Q148H/R/K alone conferred a median 0.8-fold (IQR: 0.7-1.1) reduction in DTG susceptibility. Considerably higher levels of reduced susceptibility often occurred when signature DRMs occurred with additional INSTI-associated DRMs. Conclusions: Among INSTI-naïve PLWH with VF and treatment emergent INSTI-associated DRMs, most developed one of four signature DRMs, most commonly R263K or G118R. G118R was associated with a much greater reduction in DTG susceptibility than R263K.
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- 2023
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26. Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.
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Horwitz LI, Thaweethai T, Brosnahan SB, Cicek MS, Fitzgerald ML, Goldman JD, Hess R, Hodder SL, Jacoby VL, Jordan MR, Krishnan JA, Laiyemo AO, Metz TD, Nichols L, Patzer RE, Sekar A, Singer NG, Stiles LE, Taylor BS, Ahmed S, Algren HA, Anglin K, Aponte-Soto L, Ashktorab H, Bassett IV, Bedi B, Bhadelia N, Bime C, Bind MC, Black LJ, Blomkalns AL, Brim H, Castro M, Chan J, Charney AW, Chen BK, Chen LQ, Chen P, Chestek D, Chibnik LB, Chow DC, Chu HY, Clifton RG, Collins S, Costantine MM, Cribbs SK, Deeks SG, Dickinson JD, Donohue SE, Durstenfeld MS, Emery IF, Erlandson KM, Facelli JC, Farah-Abraham R, Finn AV, Fischer MS, Flaherman VJ, Fleurimont J, Fonseca V, Gallagher EJ, Gander JC, Gennaro ML, Gibson KS, Go M, Goodman SN, Granger JP, Greenway FL, Hafner JW, Han JE, Harkins MS, Hauser KSP, Heath JR, Hernandez CR, Ho O, Hoffman MK, Hoover SE, Horowitz CR, Hsu H, Hsue PY, Hughes BL, Jagannathan P, James JA, John J, Jolley S, Judd SE, Juskowich JJ, Kanjilal DG, Karlson EW, Katz SD, Kelly JD, Kelly SW, Kim AY, Kirwan JP, Knox KS, Kumar A, Lamendola-Essel MF, Lanca M, Lee-Lannotti JK, Lefebvre RC, Levy BD, Lin JY, Logarbo BP Jr, Logue JK, Longo MT, Luciano CA, Lutrick K, Malakooti SK, Mallett G, Maranga G, Marathe JG, Marconi VC, Marshall GD, Martin CF, Martin JN, May HT, McComsey GA, McDonald D, Mendez-Figueroa H, Miele L, Mittleman MA, Mohandas S, Mouchati C, Mullington JM, Nadkarni GN, Nahin ER, Neuman RB, Newman LT, Nguyen A, Nikolich JZ, Ofotokun I, Ogbogu PU, Palatnik A, Palomares KTS, Parimon T, Parry S, Parthasarathy S, Patterson TF, Pearman A, Peluso MJ, Pemu P, Pettker CM, Plunkett BA, Pogreba-Brown K, Poppas A, Porterfield JZ, Quigley JG, Quinn DK, Raissy H, Rebello CJ, Reddy UM, Reece R, Reeder HT, Rischard FP, Rosas JM, Rosen CJ, Rouphael NG, Rouse DJ, Ruff AM, Saint Jean C, Sandoval GJ, Santana JL, Schlater SM, Sciurba FC, Selvaggi C, Seshadri S, Sesso HD, Shah DP, Shemesh E, Sherif ZA, Shinnick DJ, Simhan HN, Singh U, Sowles A, Subbian V, Sun J, Suthar MS, Teunis LJ, Thorp JM Jr, Ticotsky A, Tita ATN, Tragus R, Tuttle KR, Urdaneta AE, Utz PJ, VanWagoner TM, Vasey A, Vernon SD, Vidal C, Walker T, Ward HD, Warren DE, Weeks RM, Weiner SJ, Weyer JC, Wheeler JL, Whiteheart SW, Wiley Z, Williams NJ, Wisnivesky JP, Wood JC, Yee LM, Young NM, Zisis SN, and Foulkes AS
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- Humans, Observational Studies as Topic, Post-Acute COVID-19 Syndrome, Prospective Studies, Retrospective Studies, SARS-CoV-2, Adolescent, Adult, Multicenter Studies as Topic, COVID-19 epidemiology
- Abstract
Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis., Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms., Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options., Registration: NCT05172024., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Helen Chu reported consulting for Merck, GSK, Pfizer, Ellume, Janssen, Vindico CME, and the Bill and Melinda Gates Foundation, and receiving research support from Gates Ventures, Ellume, and Sanofi Pasteur. She also serves as a co-investigator on studies funded by Pfizer, Novavax, and GSK. Maged Costantine reported receiving grant support for work not related to RECOVER work/publications from Baxter International and Siemens Healthcare and personal consulting fees not related to this paper from Progenity, Quidel Ortho, and Siemens Healthcare. Kristine Erlandson reported research funding from Gilead Sciences and consulting payments from Gilead Sciences, Merck, and ViiV Pharmaceuticals, all paid to the University of Colorado. Emily Gallagher reported consulting for Novartis, Flare Therapeutics and Seagen. Edward Gardner reported research support (clinical trials) from Gilead Sciences, ViiV Healthcare, and Cepheid. Jason Goldman reported research support from Gilead, Eli Lilly and Regeneron; grants from Gilead, Merck (BARDA); personal fees for consulting from Gilead, Eli Lilly; and non-financial support from Adaptive Biotechnologies and Labcorp/Monogram Biosciences outside the submitted work. Timothy Heinrich reported grant support from Merck Inc. and consulting fees from Roche. Rachel Hess reported serving as Data Safety Monitoring Board member for Astellas Pharmaceuticals unrelated to the current work. Leora Horwitz reported being a member of the National Academy of Medicine Committee on the Long-Term Health Effects Stemming from COVID-19 and Implications for the Social Security Administration. Priscilla Hsue reported receiving honoraria from Gilead and Merck unrelated to study topic, receiving study drug from Regeneron unrelated to study topic, and receiving a research grant from Novartis. Judith James reported OMRF has licensed her IP to Progentec Biosciences, has received grant support from Progentec Biosciences, and serves on Advisory Committees to Glaxo Smith Klein, Merck and Novartis. Arthur Kim reports providing educational materials to Clinical Care Options and UpToDate and serving on a Data Safety Monitoring board for Kintor Pharmaceuticals, Ltd. Bruce Levy reported serving as a consultant for AstraZeneca, Entrinsic Biosciences, Gossamer Bio and Nocion Therapeutics and receiving research support from Amgen, Genentech, GlaxoSmithKline, Pieris Pharmaceuticals, SRA and Sanofi unrelated to the current work. Vincent Marconi reported receiving grants from NIH during the conduct of the study and grants from NIH, Veteran Affairs, and Centers for Disease Control and Prevention; grants, personal fees, nonfinancial support, and other from Lilly and Gilead; grants and personal fees from ViiV; and nonfinancial support from Bayer outside the submitted work. Grace McComsey reported serving as consultant for Merck, Gilead, ViiV, Janssen and have received research support from Pfizer, Vanda, Genentech, Roche, Redhill and Cognivue. Torri Metz reported being a site PI and a participant in the medical advisory board for the planning of a Pfizer clinical trial of SARS-CoV-2 vaccination in pregnancy. She also reported being a site PI for a Pfizer study evaluating the pharmacokinetics of Paxlovid in pregnant people with COVID-19. Janet Mullington reported support for investigator-initiated research by "Open Medicine Foundation and the Patient-Led Research Collaborative" Princess Ogbogu reported research support from Astrazeneca, GSK, Blueprint medical; advisory board for Astrazeneca, GSK, Sanofi, Kalvista; and consulting for Astrazeneca, GSK Sairam Parthasarathy reported research funding to Institution from Sergey Brin foundation of COVID and Long-COVID research. Michael Peluso reported consulting fees from Gilead Sciences and AstraZeneca, and service on data safety monitoring board for American Gene Technologies. Sean Quigley reported service on speaker Board for Servier, Alnylam, Agios; service on advisory board for Recordati, Alexion. Franz Rischard reported research support from NIH/NHLBI, United Therapeutics, Acceleron/Merck, Janssen, Insmed, Aerovate, and Bayer; and consulting/advisory compensation from Acceleron and Bayer. Nadine Rouphael reported being a consultant for ICON and EMMES as a safety consultant for clinical trials; service on the advisory boards for Moderna; funds to institution from Sanofi, Lilly, Merck, Quidel and Pfizer. PJ Utz reported stock ownership of Gilead and PI of biomarker studies for Pfizer STOP-PASC paxlovid trial Juan Wisnivesky received receiving consulting honorarium from Sanofi, Banook, Prospero, PPD and Atea and research grants from Sanofi, Regeneron, Axella, and Arnold Consultants., (Copyright: © 2023 Horwitz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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27. Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.
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Thaweethai T, Jolley SE, Karlson EW, Levitan EB, Levy B, McComsey GA, McCorkell L, Nadkarni GN, Parthasarathy S, Singh U, Walker TA, Selvaggi CA, Shinnick DJ, Schulte CCM, Atchley-Challenner R, Alba GA, Alicic R, Altman N, Anglin K, Argueta U, Ashktorab H, Baslet G, Bassett IV, Bateman L, Bedi B, Bhattacharyya S, Bind MA, Blomkalns AL, Bonilla H, Brim H, Bush PA, Castro M, Chan J, Charney AW, Chen P, Chibnik LB, Chu HY, Clifton RG, Costantine MM, Cribbs SK, Davila Nieves SI, Deeks SG, Duven A, Emery IF, Erdmann N, Erlandson KM, Ernst KC, Farah-Abraham R, Farner CE, Feuerriegel EM, Fleurimont J, Fonseca V, Franko N, Gainer V, Gander JC, Gardner EM, Geng LN, Gibson KS, Go M, Goldman JD, Grebe H, Greenway FL, Habli M, Hafner J, Han JE, Hanson KA, Heath J, Hernandez C, Hess R, Hodder SL, Hoffman MK, Hoover SE, Huang B, Hughes BL, Jagannathan P, John J, Jordan MR, Katz SD, Kaufman ES, Kelly JD, Kelly SW, Kemp MM, Kirwan JP, Klein JD, Knox KS, Krishnan JA, Kumar A, Laiyemo AO, Lambert AA, Lanca M, Lee-Iannotti JK, Logarbo BP, Longo MT, Luciano CA, Lutrick K, Maley JH, Mallett G, Marathe JG, Marconi V, Marshall GD, Martin CF, Matusov Y, Mehari A, Mendez-Figueroa H, Mermelstein R, Metz TD, Morse R, Mosier J, Mouchati C, Mullington J, Murphy SN, Neuman RB, Nikolich JZ, Ofotokun I, Ojemakinde E, Palatnik A, Palomares K, Parimon T, Parry S, Patterson JE, Patterson TF, Patzer RE, Peluso MJ, Pemu P, Pettker CM, Plunkett BA, Pogreba-Brown K, Poppas A, Quigley JG, Reddy U, Reece R, Reeder H, Reeves WB, Reiman EM, Rischard F, Rosand J, Rouse DJ, Ruff A, Saade G, Sandoval GJ, Santana JL, Schlater SM, Sciurba FC, Shepherd F, Sherif ZA, Simhan H, Singer NG, Skupski DW, Sowles A, Sparks JA, Sukhera FI, Taylor BS, Teunis L, Thomas RJ, Thorp JM, Thuluvath P, Ticotsky A, Tita AT, Tuttle KR, Urdaneta AE, Valdivieso D, VanWagoner TM, Vasey A, Verduzco-Gutierrez M, Wallace ZS, Ward HD, Warren DE, Weiner SJ, Welch S, Whiteheart SW, Wiley Z, Wisnivesky JP, Yee LM, Zisis S, Horwitz LI, and Foulkes AS
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- Female, Adult, Humans, Middle Aged, Male, Prospective Studies, Post-Acute COVID-19 Syndrome, Cohort Studies, Disease Progression, Fatigue, SARS-CoV-2, COVID-19 complications
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Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals., Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections., Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling., Exposure: SARS-CoV-2 infection., Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds)., Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months., Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
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- 2023
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28. HIV Drug Resistance in Adults Initiating or Reinitiating Antiretroviral Therapy in Uruguay-Results of a Nationally Representative Survey, 2018-2019.
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Flieller R, Cabrera S, Ruchansky D, Girón-Callejas A, Brasesco M, Pérez D, Chiparelli H, García-Morales C, Tapia-Trejo D, Monreal-Flores J, Ravasi G, Jordan MR, and Ávila-Ríos S
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- Male, Adult, Humans, Female, Ritonavir, Cross-Sectional Studies, Uruguay epidemiology, Anti-Retroviral Agents, HIV Infections drug therapy, HIV Infections epidemiology, HIV-1 genetics
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The first nationally representative cross-sectional HIV drug resistance (HIVDR) survey was conducted in Uruguay in 2018-2019 among adults diagnosed with HIV and initiating or reinitiating antiretroviral therapy (ART). Protease , reverse transcriptase , and integrase genes of HIV-1 were sequenced. A total of 206 participants were enrolled in the survey; 63.2% were men, 85.7% were >25 years of age, and 35.6% reported previous exposure to antiretroviral (ARV) drugs. The prevalence of HIVDR to efavirenz or nevirapine was significantly higher (OR: 1.82, p < 0.001) in adults with previous ARV drug exposure (20.3%, 95% CI: 18.7-22.0%) compared to adults without previous ARV drug exposure (12.3%, 11.0-13.8%). HIVDR to any nucleoside reverse transcriptase inhibitors was 10.3% (9.4-11.2%). HIVDR to ritonavir-boosted protease inhibitors was 1.5% (1.1-2.1%); resistance to ritonavir-boosted darunavir was 0.9% (0.4-2.1%) among adults without previous ARV drug exposure and it was not observed among adults with previous ARV drug exposure. Resistance to integrase inhibitors was 12.7% (11.7-13.8%), yet HIVDR to dolutegravir, bictegravir, and cabotegravir was not observed. The high level (>10%) of HIVDR to efavirenz highlights the need to accelerate the transition to the WHO-recommended dolutegravir-based ART. Access to dolutegravir-based ART should be prioritised for people reporting previous ARV drug exposure.
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- 2023
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29. Metal retention and replacement in QueD2 protect queuosine-tRNA biosynthesis in metal-starved Acinetobacter baumannii .
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Jordan MR, Gonzalez-Gutierrez G, Trinidad JC, and Giedroc DP
- Subjects
- Humans, Transcription, Genetic, RNA, Transfer genetics, Metals, Nucleoside Q, Acinetobacter baumannii
- Abstract
In response to bacterial infection, the vertebrate host employs the metal-sequestering protein calprotectin (CP) to withhold essential transition metals, notably Zn(II), to inhibit bacterial growth. Previous studies of the impact of CP-imposed transition-metal starvation in A. baumannii identified two enzymes in the de novo biosynthesis pathway of queuosine-transfer ribonucleic acid (Q-tRNA) that become cellularly abundant, one of which is QueD2, a 6-carboxy-5,6,7,8-tetrahydropterin (6-CPH
4 ) synthase that catalyzes the initial, committed step of the pathway. Here, we show that CP strongly disrupts Q incorporation into tRNA. As such, we compare the Ab QueD2 "low-zinc" paralog with a housekeeping, obligatory Zn(II)-dependent enzyme QueD. The crystallographic structure of Zn(II)-bound Ab QueD2 reveals a distinct catalytic site coordination sphere and assembly state relative to QueD and possesses a dynamic loop, immediately adjacent to the catalytic site that coordinates a second Zn(II) in the structure. One of these loop-coordinating residues is an invariant Cys18, that protects QueD2 from dissociation of the catalytic Zn(II) while maintaining flux through the Q-tRNA biosynthesis pathway in cells. We propose a "metal retention" model where Cys18 introduces coordinative plasticity into the catalytic site which slows metal release, while also enhancing the metal promiscuity such that Fe(II) becomes an active cofactor. These studies reveal a complex, multipronged evolutionary adaptation to cellular Zn(II) limitation in a key Zn(II) metalloenzyme in an important human pathogen.- Published
- 2022
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30. Characterization of dolutegravir drug resistance in persons diagnosed with HIV after exposure to long-acting injectable cabotegravir for preexposure prophylaxis.
- Author
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Ahluwalia AK, Inzaule S, Baggaley RC, Vitoria M, Schaefer R, Schmidt HA, Rodolph M, Giron A, and Jordan MR
- Subjects
- Diketopiperazines, Drug Resistance, Heterocyclic Compounds, 3-Ring, Humans, Oxazines, Piperazines, Pyridones therapeutic use, Rilpivirine therapeutic use, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections prevention & control, Pre-Exposure Prophylaxis
- Published
- 2022
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31. Resistance levels to non-nucleoside reverse transcriptase inhibitors among pregnant women with recent HIV infection in Malawi.
- Author
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Bello G, Kagoli M, Chipeta S, Auld A, Chang JC, DeVos JR, Kim E, Mkungudza J, Payne D, Eliya M, Nyirenda R, Jahn A, Mzumara T, Mvula B, Dadabhai S, Namakhoma I, Babaye Y, Giron A, Jordan MR, Bertagnolio S, O'Malley G, and Wadonda-Kabondo N
- Subjects
- Cross-Sectional Studies, Drug Resistance, Viral genetics, Female, HIV Reverse Transcriptase genetics, HIV Reverse Transcriptase therapeutic use, Humans, Mutation, Pregnancy, Pregnant Women, Prevalence, Reverse Transcriptase Inhibitors pharmacology, Reverse Transcriptase Inhibitors therapeutic use, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections epidemiology, HIV-1 genetics
- Abstract
Background: Information on HIV drug resistance (HIVDR) prevalence in people newly diagnosed with HIV is limited. We implemented a cross-sectional study to estimate HIVDR prevalence among pregnant women recently infected with HIV in Malawi., Methods: The HIVDR study was nested within a routine antenatal clinic (ANC) sentinel surveillance survey. Dried blood spot samples were tested for recent infection using a limiting antigen antibody assay together with HIV viral load testing. HIV-1 protease and reverse transcriptase were sequenced using Sanger sequencing. Drug susceptibility was predicted using Stanford HIVdb algorithm (version 8.9). Weighted analysis was performed in Stata 15.1., Results: Of the 21,642 pregnant women enrolled in the ANC survey, 8.4% (1826/21,642) tested HIV positive. Of these, 5.0% (92/1826) had recent HIV infection, and 90.2% (83/92) were tested by PCR. The amplification and sequencing success rate was 57.8% (48/83). The prevalence of any HIVDR was 14.6% (5/45) (95% CI: 4.7-36.8%), all of which indicated HIVDR to nonnucleoside reverse transcriptase inhibitors (NNRTIs). HIVDR to nucleoside reverse transcriptase inhibitors was 7.9% (2/45) (95% CI: 1.4-34.6%). Resistance to protease inhibitors currently in use in Malawi was not observed., Conclusions: Despite the low number of cases with presumed TDR, our study hints that resistance to NNRTIs was high, above the 10% target for regimen change. Further investigation is needed to establish the exact magnitude of presumed TDR among women recently infected with HIV. These findings support the transition to an integrase inhibitor-based first-line regimen for patients initiating or on ART.
- Published
- 2022
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32. HIV and SARS-CoV-2: the interplay of two wicked problems.
- Author
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Kiekens A, Bwire GM, Decouttere C, Jordan MR, Mangara A, Mosha IH, Rinke de Wit T, Sangeda RZ, Swalehe O, Vandaele N, Killewo J, and Vandamme AM
- Subjects
- Humans, Risk Factors, SARS-CoV-2, COVID-19, HIV Infections epidemiology
- Abstract
Competing Interests: Competing interests: A-MV declares consultancy fees from Gilead.
- Published
- 2022
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33. Determining the acceptability of point-of-care urine tenofovir testing and its performance in predicting HIV RNA suppression.
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Marryshow TA, Muhairwe J, Tang A, Molulela MMM, Matta R, and Jordan MR
- Subjects
- Humans, Point-of-Care Systems, Point-of-Care Testing, RNA, Tenofovir therapeutic use, Tenofovir urine, Anti-HIV Agents therapeutic use, HIV Infections diagnosis, HIV Infections drug therapy, HIV Infections prevention & control, Pre-Exposure Prophylaxis
- Abstract
Background: The detection of tenofovir (TFV) metabolites by point-of-care (POC) urine lateral flow immunoassays (LFIA) indicates adherence to tenofovir-containing HIV pre-exposure prophylaxis. However, the association between urine TFV metabolites as detected by LFIA and HIV viral load suppression in people receiving TFV-based antiretroviral therapy (ART) is unknown as is patient and clinician acceptability of POC urine LFIA testing in clinical practice in low- and middle-income country settings., Methods: We enrolled 409 people living with HIV from two HIV clinics in Lesotho and investigated the performance of POC urine LFIA TFV testing in predicting viral suppression. We interviewed 12 study participants and conducted a focus-group discussion with 5 clinicians to gather opinions on POC urine TFV testing., Results: Using a viral load threshold of 1000 copies/mL, 398 (98%) participants were virologically suppressed, and 8 were viremic. Tenofovir was detected in the urine of 405 (99%) participants. The sensitivity of the POC urine LFIA test in detecting TFV in participants with viral suppression was 99.3% (95% CI: 97.8-99.8); the specificity was 12.5% (95% CI: 0.3-52.6). The positive and negative predictive values were 98.3% and 25%, respectively. Point-of-care urine TFV testing was viewed favorably by both participants and clinicians. However, clinicians stated that the 2-3-days detection window of the assay studied limits adherence categorization., Conclusions: In our study cohort, urine POC TFV testing demonstrated high sensitivity in predicting viral suppression, but low specificity and negative predictive value. Urine POC TFV testing was highly acceptable to participants and clinicians; however, clinicians expressed concern about its clinical utility because of its limitations. While further research is needed to assess performance in less adherent populations, this test may support adherence counseling in some clinical settings.
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- 2022
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34. Corporate insecthood.
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Strohminger N and Jordan MR
- Subjects
- Animals, Humans, Morals, Personhood
- Abstract
Whether the corporation should be considered a person is a matter of active academic and public debate. Here, we examine whether, and in what ways, ordinary citizens conceptualize the corporation as a person. We present evidence that corporations are anthropomorphized, but only to a certain degree. Compared with other entities, the average corporation is considered about as similar to a person as an ant. Corporations differ in the extent to which people are willing to grant them personhood however, and this pattern is predicted by how salient the organization's mental and moral traits are. This process of anthropomorphization has important downstream consequences, increasing support for granting legal rights and responsibilities to corporations. Because our studies show that this relationship also obtains for animals, we conclude that perceptions of corporate personhood draw on a more general set of rules for assessing an entity's personhood., (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Published
- 2022
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35. Epidemiology of HIV drug resistance in low- and middle-income countries and WHO global strategy to monitor its emergence.
- Author
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Bertagnolio S, Jordan MR, Giron A, and Inzaule S
- Subjects
- Adult, Developing Countries, Humans, Reverse Transcriptase Inhibitors therapeutic use, Viral Load, World Health Organization, Anti-HIV Agents therapeutic use, Drug Resistance, Viral, HIV Infections drug therapy, HIV Infections epidemiology
- Abstract
Purpose of Review: This review summarises the latest information of the epidemiology of HIV drug resistance (HIVDR) in low- and middle-income countries and the updated WHO global strategy for HIVDR surveillance and monitoring., Recent Findings: Finding from recent national-representative surveys show a rise in pretreatment drug resistance (PDR) to reverse transcriptase inhibitors and especially to the class of nonnucleoside reverse transcriptase inhibitors. Levels of PDR are especially high in infants <18 months and adults reporting prior exposure to antiretrovirals. Although viral suppression rates are generally high and increasing among adults on antiretroviral therapy, those with unsuppressed viremia have high levels of acquired drug resistance (ADR). Programmatic data on HIVDR to integrase-transfer-inhibitor resistance is scarce, highlighting the need to increase integrase-inhibitors resistance surveillance. As the landscape of HIV prevention, treatment and monitoring evolves, WHO has also adapted its strategy to effectively support countries in preventing and monitoring the emergence of HIVDR. This includes new survey methods for monitoring resistance emerging from patients diagnosed with HIV while on preexposure prophylaxis, and a laboratory-based ADR survey leveraging on remnant viral load specimens which are expected to strengthen dolutegravir-resistance surveillance., Summary: Monitoring HIVDR remains pivotal to ensure countries attain and sustain the global goals for ending HIV as a public health threat by 2030., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
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36. Zn-regulated GTPase metalloprotein activator 1 modulates vertebrate zinc homeostasis.
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Weiss A, Murdoch CC, Edmonds KA, Jordan MR, Monteith AJ, Perera YR, Rodríguez Nassif AM, Petoletti AM, Beavers WN, Munneke MJ, Drury SL, Krystofiak ES, Thalluri K, Wu H, Kruse ARS, DiMarchi RD, Caprioli RM, Spraggins JM, Chazin WJ, Giedroc DP, and Skaar EP
- Subjects
- Animals, GTP Phosphohydrolases metabolism, Homeostasis, Metallochaperones metabolism, Metalloproteins genetics, Mice, Zebrafish metabolism, Metalloendopeptidases metabolism, Zinc metabolism
- Abstract
Zinc (Zn) is an essential micronutrient and cofactor for up to 10% of proteins in living organisms. During Zn limitation, specialized enzymes called metallochaperones are predicted to allocate Zn to specific metalloproteins. This function has been putatively assigned to G3E GTPase COG0523 proteins, yet no Zn metallochaperone has been experimentally identified in any organism. Here, we functionally characterize a family of COG0523 proteins that is conserved across vertebrates. We identify Zn metalloprotease methionine aminopeptidase 1 (METAP1) as a COG0523 client, leading to the redesignation of this group of COG0523 proteins as the Zn-regulated GTPase metalloprotein activator (ZNG1) family. Using biochemical, structural, genetic, and pharmacological approaches across evolutionarily divergent models, including zebrafish and mice, we demonstrate a critical role for ZNG1 proteins in regulating cellular Zn homeostasis. Collectively, these data reveal the existence of a family of Zn metallochaperones and assign ZNG1 an important role for intracellular Zn trafficking., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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37. Public availability of HIV-1 drug resistance sequence and treatment data: a systematic review.
- Author
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Rhee SY, Kassaye SG, Jordan MR, Kouamou V, Katzenstein D, and Shafer RW
- Subjects
- Adult, Child, Drug Resistance, Viral genetics, Humans, Mutation, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Seropositivity drug therapy, HIV-1 genetics
- Abstract
HIV-1 pol sequences from antiretroviral therapy (ART)-naive and ART-experienced people living with HIV-1 are fundamental to understanding the genetic correlates and epidemiology of HIV-1 drug resistance (HIVDR). To assess the public availability of HIV-1 pol sequences and ART histories of the individuals from whom sequenced viruses were obtained, we performed a systematic review of PubMed and GenBank for HIVDR studies published between 2010 and 2019 that reported HIV-1 pol sequences. 934 studies met inclusion criteria, including 461 studies of ART-naive adults, 407 of ART-experienced adults, and 66 of ART-naive and ART-experienced children. Sequences were available for 317 (68·8%) studies of ART-naive individuals, 190 (46·7%) of ART-experienced individuals, and 45 (68·2%) of children. Among ART-experienced individuals, sequences plus linked ART histories were available for 82 (20·1%) studies. Sequences were available for 21 (29·2%) of 72 clinical trials. Among journals publishing more than ten studies, the proportion with available sequences ranged from 8·3% to 86·9%. Strengthened implementation of data sharing policies is required to increase the number of studies with available HIVDR data to support the enterprise of global ART in the face of emerging HIVDR., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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38. Weakness After an Intra-articular Steroid Injection: A Case Report of Acute Steroid-induced Myopathy.
- Author
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Jordan MR, Hensley LA, and Jackson ML
- Abstract
Introduction: Weakness is a common chief complaint in the emergency department, and the use of glucocorticoids is pervasive in medicine. Muscle weakness, or myopathy, is a well documented side effect of chronic glucocorticoid use. However, acute myopathy, with an onset shortly after initiation of glucocorticoids, is much rarer., Case Report: We present a case of acute steroid-induced myopathy after a single intra-articular dose of triamcinolone in a young, healthy, active male. To our knowledge, this is the first case described in the medical literature of acute steroid-induced myopathy following a single intra-articular injection., Conclusion: In a patient who presents with proximal muscle weakness and has a history of glucocorticoid use, the diagnosis of steroid-induced myopathy should be considered. Acute steroid-induced myopathy should be high on the differential in a patient who presents with typical symptoms and has been prescribed glucocorticoids for less than 14 days or, in rare cases, may have recently received a single dose of glucocorticoids. Treatment is supportive and outpatient management is typically indicated, as respiratory muscle involvement is rare.
- Published
- 2022
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39. Predictors of loss to follow-up from HIV antiretroviral therapy in Namibia.
- Author
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Hong SY, Winston A, Mutenda N, Hamunime N, Roy T, Wanke C, Tang AM, and Jordan MR
- Subjects
- Adult, Anti-Retroviral Agents therapeutic use, Female, Follow-Up Studies, Humans, Lost to Follow-Up, Male, Namibia epidemiology, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections epidemiology
- Abstract
Despite progress on population-level HIV viral suppression, unknown outcomes amongst people who have initiated antiretroviral therapy (ART) in low- and middle-income countries, commonly referred to as loss to follow-up (LTFU), remains a barrier. The mean global estimate of LTFU is 20%, exceeding the World Health Organization target of <15%. Pervasive predictors associated with LTFU include younger age, low body mass index, low CD4 count, advanced HIV clinical stage and certain ART regimens. In Namibia, ART use by eligible individuals exceeds 85%, surpassing the global average. Nonetheless, LTFU remains a barrier to achieving viral suppression and requires research to elucidate context-specific factors. An observational cohort study was conducted in Namibia in 2012 by administering surveys to individuals who presented for HIV care and initiated ART for the first time. Additional data were collected from routine medical data monitoring systems. Participants classified as LTFU at 12 months were traced to confirm their status. Predictors of LTFU were analyzed using multivariable logistic regression. Of those who presented consecutively to initiate ART, 524 were identified as eligible to enroll in the study, 497 enrolled, and 474 completed the baseline questionnaire. The cohort had mean age 36 years, 39% were male, mean CD4 cell count 222 cells/mm3, 17% were WHO HIV clinical stage III-IV, and 14% started efavirenz-based regimens. Tracing participants classified as LTFU yielded a re-categorization from 27.8% (n = 132) to 14.3% (n = 68) LTFU. In the final multivariable model, factors associated with confirmed LTFU status were: younger age (OR 0.97, 95% CI 1.00-1.06, p = 0.02); male sex (OR 2.34, CI 1.34-4.06, p = 0.003); difficulty leaving work or home to attend clinic (OR 2.55, CI 1.40-4.65, p = 0.002); and baseline efavirenz-based regimen (OR 2.35, CI 1.22-4.51, p = 0.01). Interventions to reduce LTFU should therefore target young men, particularly those who report difficulty leaving work or home to attend clinic and are on an efavirenz-based regimen., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
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40. Pretreatment Human Immunodeficiency Virus (HIV) Drug Resistance Among Treatment-Naive Infants Newly Diagnosed With HIV in 2016 in Namibia: Results of a Nationally Representative Study.
- Author
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Jordan MR, Bikinesi L, Ashipala L, Mutenda N, Brantuo M, Hunt G, Shiningavamwe A, Mutandi G, Beukes A, Beard S, Battey K, Dziuban EJ, Raizes E, Adjei P, Tang A, Giron A, and Hong SY
- Abstract
Background: The World Health Organization (WHO) recommends routine surveillance of pretreatment human immunodeficiency virus (HIV) drug resistance (HIVDR) in children <18 months of age diagnosed with HIV through early infant diagnosis (EID). In 2016, 262 children <18 months of age were diagnosed with HIV in Namibia through EID. Levels of HIVDR in this population are unknown., Methods: In 2016, Namibia surveyed pretreatment HIVDR among children aged <18 months following WHO guidance. Reverse transcriptase, protease, and integrase regions of HIV-1 were genotyped from remnant dried blood spot specimens from all infants diagnosed with HIV in Namibia in 2016. HIVDR was predicted using the Stanford HIVdb algorithm., Results: Of 262 specimens genotyped, 198 HIV-1 protease and reverse transcriptase sequences and 118 HIV-1 integrase sequences were successfully amplified and analyzed. The prevalence of efavirenz/nevirapine (EFV/NVP), abacavir (ABC), zidovudine, lamivudine/emtricitabine (3TC/FTC), and tenofovir (TDF) resistance was 62.6%, 17.7%, 5.6%, 15.7%, and 10.1%, respectively. No integrase inhibitor resistance was detected., Conclusions: The high level of EFV/NVP resistance is unsurprising; however, levels of ABC and TDF resistance are among the highest observed to date in infants in sub-Saharan Africa. The absence of resistance to dolutegravir (DTG) is reassuring but underscores the need to further study the impact of ABC and 3TC/FTC resistance on pediatric protease inhibitor- and DTG-based regimens and accelerate access to other antiretroviral drugs. Results underscore the need for antiretroviral therapy optimization and prompt management of high viral loads in infants and pregnant and breastfeeding women., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2022
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41. Impact of nucleos(t)ide reverse transcriptase inhibitor resistance on dolutegravir and protease-inhibitor-based regimens in children and adolescents in Kenya.
- Author
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Kingwara L, Inzaule SC, Momanyi L, Jordan MR, Nyanya W, Bowen N, Oramisi V, Kiiru JN, and Ngugi C
- Subjects
- Adolescent, Child, Heterocyclic Compounds, 3-Ring therapeutic use, Humans, Kenya, Lamivudine therapeutic use, Oxazines, Peptide Hydrolases, Piperazines, Protease Inhibitors therapeutic use, Pyridones therapeutic use, Reverse Transcriptase Inhibitors therapeutic use, Tenofovir therapeutic use, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV-1
- Abstract
We assessed the impact of using dolutegravir or a protease inhibitor with an inactive nucleoside-reverse transcriptase inhibitor (NRTI) in children and adolescents. We observed high-levels of viral suppression among those on tenofovir-lamivudine-dolutegravir even in presence of an inactive NRTI backbone but lower levels among those on protease inhibitors, especially those retained on an inactive abacavir. Although tenofovir may be recycled with dolutegravir, more studies are needed to determine if abacavir can be reused with dolutegravir or protease inhibitors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
- Full Text
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42. Community Assessment for Public Health Emergency Response (CASPER) Following Hurricane Michael, Bay and Gulf Counties, Florida, 2019.
- Author
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Rodriguez E, Duclos C, Joiner J, Jordan M, Reid K, and Kintziger KW
- Subjects
- Bays, Florida, Humans, Needs Assessment, Public Health, Cyclonic Storms
- Abstract
Context: On October 10, 2018, Hurricane Michael made landfall near Mexico Beach, Florida, as one of the strongest storms on record to hit the US mainland. Hurricane Michael brought strong winds, heavy rain, and life-threatening storm surge, causing extensive damage across the Florida Panhandle., Objectives: To assess community preparedness and effects experienced by Panhandle residents, including structural and economic losses, injury and illness, health care access, and suicide risk and ideation in the counties most severely impacted by Hurricane Michael., Design: The Florida Department of Health conducted a Community Assessment for Public Health Emergency Response (CASPER) in October and November 2019, a year after Hurricane Michael made landfall. CASPER is a 2-stage cluster sampling method designed to provide household-level information about a community's needs in a timely, inexpensive, and representative manner., Setting: A total of 30 clusters were randomly selected from Bay and Gulf Counties, Florida., Participants: In total, 178 face-to-face interviews were completed with adult residents 18 years or older., Main Outcome Measures: Hurricane-related impacts, including structural and economic losses, injury and illness, health care access; and mental health., Results: Almost half of respondents did not evacuate despite mandatory evacuation orders. Most houses (78.1%) received some damage, with more than half still not repaired 1 year later. Access to emergency supply kits, water, nonperishable foods, medications, and health care was common, though many reported needing supplies not included in their kit. Less than half reported having working household carbon monoxide detectors. Injuries and illnesses associated with the hurricane were uncommon; however, anxiety, depression, and insomnia were reported as occurring or worsening by more than one-third of respondents posthurricane., Conclusions: Increased education and communication regarding hurricane preparedness and recovery, which include clearer messaging on evacuation, improving emergency supply kits, importance of carbon monoxide detectors, and proper generator use, could enhance the safety of the community., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
- Full Text
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43. The prevalence of pre-treatment and acquired HIV drug resistance in Vietnam: a nationally representative survey, 2017-2018.
- Author
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Dat VQ, Anh NTL, Van Nghia K, Linh NT, Thu HHK, Tam TTM, Ton T, Anh LQ, Phuc ND, Huong PTT, Nhan DT, Hai NH, Bertagnolio S, Crisp AM, Inzaule S, Dean NE, Jordan MR, and Nguyen VTT
- Subjects
- Drug Resistance, Viral, Humans, Prevalence, Vietnam epidemiology, Viral Load, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections epidemiology
- Abstract
Introduction: Monitoring the population-level emergence and transmission of HIV drug resistance (HIVDR) is necessary for supporting public health programmes. This study provides a nationally representative prevalence estimate of HIVDR in people initiating antiretroviral therapy (ART) and estimates of acquired HIVDR and viral load (VL) suppression in people who have received it for 12 or ≥48 months in Vietnam., Methods: The study was conducted between September 2017 and March 2018 following World Health Organization guidance. Thirty ART clinics were randomly sampled using probability proportional to size sampling from a total of 367 ART clinics in the country., Results and Discussion: In total, 409 patients initiating ART were enrolled into the survey of pre-treatment HIVDR. The prevalence of any pre-treatment HIVDR was 5.8% (95% CI 3.4-9.5%), and the prevalence of non-nucleoside reverse transcriptase inhibitor resistance was 3.4% (95% CI 1.8-6.2%). Four hundred twenty-nine patients on ART for 12±3 months and 723 patients on ART for ≥48 months were enrolled into the surveys of acquired HIVDR. The prevalence of VL suppression (defined as <1000 copies/ml) in patients on ART for 12±3 and ≥48 months was 95.5% (95% CI 91.3-97.8%) and 96.1% (95% CI 93.2-97.8%), respectively. Among individuals with viral non-suppression, any HIVDR was detected in 11/14 (weighted prevalence 74.3%) of those on ART for 12±3 months and in 24/27 (weighted prevalence 88.5%) of those receiving ART for ≥48 months., Conclusions: This nationally representative study of HIVDR found high levels of VL suppression among those on ART for 12 and ≥48 months. Overall, high levels of VL suppression at both time points suggested good adherence among patients receiving ART and quality of treatment services in Vietnam., Clinical Trial Number: Not applicable., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)
- Published
- 2022
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44. Naloxone
- Author
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Jordan MR and Morrisonponce D
- Abstract
Over the past two decades, the rate of overdose from opiates has increased significantly. Opiate misuse is associated with enormous morbidity and mortality; people are reportedly overdosing on opioids nationwide. Naloxone has been the only antidote to opioids for over 50 years, and the drug has been readily available as a parenteral formula. The belief is that naloxone acts as a pure mu-opiate receptor competitive antagonist. Besides being available in hospitals, the drug is carried by emergency medical staff as well as law enforcement personnel. Also, the availability of naloxone over the counter has made it easier for family members and caregivers of those with opioid misuse disorder to administer the drug. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, monitoring, and toxicity of naloxone, so providers can direct patient therapy to optimal outcomes when opioid toxicity is an issue., (Copyright © 2022, StatPearls Publishing LLC.)
- Published
- 2022
45. Asystole
- Author
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Jordan MR, Lopez RA, and Morrisonponce D
- Abstract
Asystole, colloquially referred to as flatline, represents the cessation of electrical and mechanical activity of the heart. Asystole typically occurs as a deterioration of the initial non-perfusing ventricular rhythms: ventricular fibrillation (V-fib) or pulseless ventricular tachycardia (V-tach). Additionally, pulseless electrical activity (PEA) can cease and become asystole. Victims of sudden cardiac arrest who present with asystole as the initial rhythm have an extremely poor prognosis (10% survive to admission, 0 to 2% survival-to-hospital discharge rate). Asystole represents the terminal rhythm of a cardiac arrest. In out-of-hospital cardiac arrest, prolonged resuscitation efforts in a patient who presents in asystole are unlikely to provide a medical benefit. Termination of resuscitation efforts should be considered in these patients, in consultation with online medical direction, as allowed by local protocols. The American College of Emergency Physicians (ACEP) and National Association of Emergency Medical Services Physicians (NAEMSP) both recommend emergency medical services systems and have written protocols that allow for termination of resuscitation efforts by emergency medical services providers for a select group of patients in which further resuscitative measures and transport to the local emergency department would be considered futile., (Copyright © 2022, StatPearls Publishing LLC.)
- Published
- 2022
46. COG0523 proteins: a functionally diverse family of transition metal-regulated G3E P-loop GTP hydrolases from bacteria to man.
- Author
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Edmonds KA, Jordan MR, and Giedroc DP
- Subjects
- Animals, Bacterial Proteins genetics, GTP Phosphohydrolases genetics, Genomics, Humans, Hydrolases genetics, Metallochaperones genetics, Mice, Transition Elements, Bacteria metabolism, Bacterial Proteins metabolism, Biological Evolution, GTP Phosphohydrolases metabolism, Hydrolases metabolism, Metallochaperones metabolism, Metals metabolism
- Abstract
Transition metal homeostasis ensures that cells and organisms obtain sufficient metal to meet cellular demand while dispensing with any excess so as to avoid toxicity. In bacteria, zinc restriction induces the expression of one or more Zur (zinc-uptake repressor)-regulated Cluster of Orthologous Groups (COG) COG0523 proteins. COG0523 proteins encompass a poorly understood sub-family of G3E P-loop small GTPases, others of which are known to function as metallochaperones in the maturation of cobalamin (CoII) and NiII cofactor-containing metalloenzymes. Here, we use genomic enzymology tools to functionally analyse over 80 000 sequences that are evolutionarily related to Acinetobacter baumannii ZigA (Zur-inducible GTPase), a COG0523 protein and candidate zinc metallochaperone. These sequences segregate into distinct sequence similarity network (SSN) clusters, exemplified by the ZnII-Zur-regulated and FeIII-nitrile hydratase activator CxCC (C, Cys; X, any amino acid)-containing COG0523 proteins (SSN cluster 1), NiII-UreG (clusters 2, 8), CoII-CobW (cluster 4), and NiII-HypB (cluster 5). A total of five large clusters that comprise ≈ 25% of all sequences, including cluster 3 which harbors the only structurally characterized COG0523 protein, Escherichia coli YjiA, and many uncharacterized eukaryotic COG0523 proteins. We also establish that mycobacterial-specific protein Y (Mpy) recruitment factor (Mrf), which promotes ribosome hibernation in actinomycetes under conditions of ZnII starvation, segregates into a fifth SSN cluster (cluster 17). Mrf is a COG0523 paralog that lacks all GTP-binding determinants as well as the ZnII-coordinating Cys found in CxCC-containing COG0523 proteins. On the basis of this analysis, we discuss new perspectives on the COG0523 proteins as cellular reporters of widespread nutrient stress induced by ZnII limitation., (© The Author(s) 2021. Published by Oxford University Press.)
- Published
- 2021
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47. Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor-Containing Antiretroviral Therapy: A Systematic Review and Meta-analysis.
- Author
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Bertagnolio S, Hermans L, Jordan MR, Avila-Rios S, Iwuji C, Derache A, Delaporte E, Wensing A, Aves T, Borhan ASM, Leenus A, Parkin N, Doherty M, Inzaule S, and Mbuagbaw L
- Subjects
- Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, Humans, Reverse Transcriptase Inhibitors therapeutic use, Viral Load drug effects, Drug Resistance, Viral drug effects, HIV Infections drug therapy, HIV-1 drug effects, HIV-1 genetics
- Abstract
Background: Increased access to antiretroviral therapy (ART) has resulted in rising levels of pretreatment human immunodeficiency virus drug resistance (PDR). This is the first systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, including the combination of efavirenz (EFV), tenofovir (TDF), and lamivudine or emtricitabine (XTC)., Methods: We systematically reviewed studies and conference proceedings comparing treatment outcomes in populations initiating NNRTI-based ART with and without PDR. We conducted subgroup analyses by regimen: (1) NNRTIs + 2 nucleoside reverse transcriptase inhibitors (NRTIs), (2) EFV + 2 NRTIs, or (3) EFV/TDF/XTC; by population (children vs adults); and by definition of resistance (PDR vs NNRTI PDR)., Results: Among 6197 studies screened, 32 were analyzed (31 441 patients). We found that individuals with PDR initiating NNRTIs across all the subgroups had increased risk of virological failure compared to those without PDR. Risk of acquisition of new resistance mutations and ART switch was also higher in people with PDR., Conclusions: This review shows poorer treatment outcomes in the presence of PDR, supporting the World Health Organization's recommendation to avoid using NNRTIs in countries where levels of PDR are high., (© World Health Organization, 2020. All rights reserved. The World Health Organization has granted the Publisher permission for the reproduction of this article.)
- Published
- 2021
- Full Text
- View/download PDF
48. High-Fidelity Wrist Fracture Phantom as a Training Tool to Develop Competency in Orthopaedic Surgical Trainees.
- Author
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Raeker-Jordan EA, Martinez M, Aziz KT, Miles MR, Means KR Jr, LaPorte DM, Giladi AM, and Shimada K
- Subjects
- Clinical Competence, Humans, Wrist, Internship and Residency, Orthopedics education, Radius Fractures
- Abstract
Background: This article will describe the development of a low-cost 3D-printed medical phantom of the arm with a distal radius fracture (DRF) to facilitate training of reduction and splinting techniques. The phantom incorporates tactile responses and visual stimuli from fluoroscopy to assist skill acquisition in a clinical setting. This provides feedback to trainees to help them develop competency and knowledge before providing care to patients., Methods: Phantoms were developed through advice and feedback from fellowship-trained hand surgeons and orthopaedic senior and junior residents. Phantoms were then pilot tested during a surgical skills examination, with residents having minimal previous exposure to distal radial reduction techniques. Residents were evaluated on procedure speed and accuracy by attending surgeons using the objective structured assessment of technical skills. Residents then completed a written knowledge examination about relevant requirements of DRF management and feedback on their opinion of the exercise using the Likert scale., Results: Residents who passed the hands-on examination also scored higher on the written examination. All residents reported that the phantom was beneficial and motivating as part of their overall training., Discussion: Real-time feedback using a phantom limb and fluoroscopic imaging, in conjunction with guidance from surgeons, allows residents to learn and practice DRF reduction and splinting techniques. These educational exercises are relatively low-cost and remove the risk of potential harm to patients during early skill acquisition. This training method may be a predictor of surgical performance in addition to providing assessment of background knowledge. Additional training sessions will be required to determine the effect of repeat exposure to residents' proficiency and comprehension., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)
- Published
- 2021
- Full Text
- View/download PDF
49. Effect of the Helping Babies Breathe Training Program: An Experimental Study on Jordanian Midwives' Knowledge and Skills.
- Author
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Hatamleh R, Abujilban S, Abuhammad S, Ariag DMA, and Joseph RA
- Subjects
- Clinical Competence, Curriculum, Female, Humans, Pregnancy, Resuscitation, Midwifery
- Abstract
The Helping Babies Breathe (HBB) training program trains providers in effective resuscitation of infants in developing countries. This study evaluated the effectiveness of the HBB training program on midwives' knowledge and skills in Northern Jordan. Using a nonequivalent control group design, 50 midwives (control, n = 25; experimental, n = 25) from 3 public hospitals in Northern Jordan were recruited and their knowledge and skills were evaluated before and after the training. The program has 3 aspects: 2 hours of teaching, 1 hour of testing, and 25 minutes of skills assessment per participant. The skills were tested individually for each participant, and they were reevaluated at 8 months after. The control and experimental groups significantly differed in posttest scores on knowledge, Objective Structured Clinical Examination A and B skills, and bag-mask application after adjusting for covariates. The HBB training program significantly enhanced knowledge of midwives in the experimental group (P < .05) and demonstrated skills. The HBB training program was helpful in improving midwives' knowledge and practices on immediate care of a newborn baby. Therefore, training midwives using the HBB training program can improve their knowledge and skills and thereby improve infant outcomes in Jordan., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
50. Distinct correlates of empathy and compassion with burnout and affective symptoms in health professionals and students.
- Author
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Romani-Sponchiado A, Jordan MR, Stringaris A, and Salum GA
- Subjects
- Affective Symptoms, Cross-Sectional Studies, Humans, Students, Surveys and Questionnaires, Burnout, Professional, Empathy
- Abstract
Objective: The causes of high rates of psychological distress among health professionals and students are largely unknown. Health professionals respond to those who are in distress with empathy (feeling what others feel) or compassion (caring about what others feel). This study aims to investigate whether empathy and compassion are distinct traits and how both traits are associated with negative affect (burnout, depression, anxiety and anger symptoms) in undergraduate students and professionals in medicine, psychology and nursing., Methods: A sample of 464 students and professionals filled out an online protocol with a sociodemographic data questionnaire and self-report questionnaires covering the variables of interest., Results: The findings indicate that empathy is associated with higher negative affect, while compassion is associate with lower negative affect, which suggests that they are different traits., Conclusion: Our findings provide new evidence that the well-being of health professionals might be affected differently depending on socioemotional traits relevant to emotional connection.
- Published
- 2021
- Full Text
- View/download PDF
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