scholarly journals HIV Pretreatment Drug Resistance Trends in Mexico City, 2017–2020

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1587
Author(s):  
Claudia García-Morales ◽  
Daniela Tapia-Trejo ◽  
Margarita Matías-Florentino ◽  
Verónica Sonia Quiroz-Morales ◽  
Vanessa Dávila-Conn ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mexico City ◽  
Drug Users ◽  
Second Generation ◽  
Care Center ◽  
Primary Care Center ◽  
Strand Transfer ◽  
Hiv Diagnosis ◽  
Lower Education Level ◽  
Lost To Follow Up

In response to increasing pretreatment drug resistance (PDR), Mexico changed its national antiretroviral treatment (ART) policy, recommending and procuring second-generation integrase strand-transfer inhibitor (INSTI)-based regimens as preferred first-line options since 2019. We present a four-year observational study describing PDR trends across 2017–2020 at the largest HIV diagnosis and primary care center in Mexico City. A total of 6688 baseline protease-reverse transcriptase and 6709 integrase sequences were included. PDR to any drug class was 14.4% (95% CI, 13.6–15.3%). A significant increasing trend for efavirenz/nevirapine PDR was observed (10.3 to 13.6%, p = 0.02). No increase in PDR to second-generation INSTI was observed, remaining under 0.3% across the study period. PDR was strongly associated with prior exposure to ART (aOR: 2.9, 95% CI: 1.9–4.6, p < 0.0001). MSM had higher odds of PDR to efavirenz/nevirapine (aOR: 2.0, 95% CI: 1.0–3.7, p = 0.04), reflecting ongoing transmission of mutations such as K103NS and E138A. ART restarters showed higher representation of cisgender women and injectable drug users, higher age, and lower education level. PDR to dolutegravir/bictegravir remained low in Mexico City, although further surveillance is warranted given the short time of ART optimization. Our study identifies demographic characteristics of groups with higher risk of PDR and lost to follow-up, which may be useful to design differentiated interventions locally.

A Retrospective Cohort Study of SARS-CoV-2 Infection in Hypertenses Patients in a Primary Care Center

2020 ◽  
Author(s):  
Esther Hernandez Castilla ◽  
Lucia Vallejo Serrano ◽  
Monica Saenz Ausejo ◽  
Beatriz Pax Sanchez ◽  
Katharina Ramrath ◽  
...  
Keyword(s):  
Primary Care ◽  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Care Center ◽  
Primary Care Center

KNOWLEDGE, ATTITUDE, AND PRACTICE OF PHARMACISTS ABOUT PHARMACEUTICAL CARE FOR DIABETES MELLITUS PATIENTS IN A PRIMARY CARE CENTER IN SAUDI ARABIA

2020 ◽  
Vol 76 (3) ◽  
Author(s):  
Maha Aldraimly ◽  
Sayed Azhar Suliman ◽  
Ahmed Ibrahim Nouri ◽  
Manahel Mohammed Alshaer ◽  
Norah Mohammed Almaghrabi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Primary Care ◽  
Saudi Arabia ◽  
Pharmaceutical Care ◽  
Care Center ◽  
Primary Care Center ◽  
Attitude And Practice ◽  
Knowledge Attitude And Practice

A Critical Review of Second-generation anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Daniel Sur ◽  
Andrei Havasi ◽  
Alecsandra Gorzo ◽  
Claudia Burz
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Second Generation ◽  
Current Data ◽  
Braf Mutations ◽  
Durable Response ◽  
Ongoing Research

Background: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. Objective: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. Conclusion: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.

Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir

2020 ◽  
Author(s):  
Hanh T Pham ◽  
Brunna M Alves ◽  
Sunbin Yoo ◽  
Meng A Xiao ◽  
Jing Leng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Binding ◽  
Drug Resistant ◽  
Strand Transfer ◽  
Viral Genomes ◽  
Proviral Dna ◽  
Viral Loads ◽  
Subtype B ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Objectives The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. Our objective was to study the effects of these substitutions. Methods Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results. Results R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints. Conclusions Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.

scholarly journals Primary drug resistance in antiretroviral-naïve injection drug users

2009 ◽  
Vol 13 (5) ◽  
pp. 577-583 ◽  
Author(s):  
Harout K. Tossonian ◽  
Jesse D. Raffa ◽  
Jason Grebely ◽  
Mark Viljoen ◽  
Annabel Mead ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Injection Drug Users ◽  
Drug Users ◽  
Injection Drug ◽  
Primary Drug Resistance ◽  
Primary Drug

Primary HIV-1 Drug Resistance and Polymorphic Patterns Among Injecting Drug Users (IDUs) in Chennai, Southern India

2009 ◽  
Vol 8 (5) ◽  
pp. 323-327 ◽  
Author(s):  
H. Syed Iqbal ◽  
Sunil S. Solomon ◽  
Vidya Madhavan ◽  
Suniti Solomon ◽  
P. Balakrishnan
Keyword(s):  
Drug Resistance ◽  
Drug Users ◽  
Injecting Drug Users ◽  
Southern India ◽  
Hiv 1

scholarly journals Brigatinib versus other second-generation ALK inhibitors as initial treatment of anaplastic lymphoma kinase positive non-small cell lung cancer with deep phenotyping: study protocol of the ABP trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Petros Christopoulos ◽  
Farastuk Bozorgmehr ◽  
Lena Brückner ◽  
Inn Chung ◽  
Johannes Krisam ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Anaplastic Lymphoma Kinase ◽  
Second Generation ◽  
Search Query ◽  
Alk Inhibitors ◽  
Anaplastic Lymphoma ◽  
Link Type ◽  
Biomarker Analysis ◽  
Nsclc Patients

Abstract Background Availability of potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) has pushed the median survival of ALK+ non-smallcell lung cancer (NSCLC) patients to over five years. In particular, second-generation ALK TKI have demonstrated superiority compared to the first-generation compound crizotinib and are meanwhile standard first-line treatment. However, clinical courses of individual patients vary widely, with secondary development of drug resistance and intracranial progression remaining important problems. While these limitations highlight the need for better disease monitoring and additional therapeutic tools, molecular tumor features are increasingly recognized as crucial determinants of clinical outcome. This trial aims to optimize management of ALK+ NSCLC by analyzing the efficacy of second-generation ALK inhibitors in conjunction with deep longitudinal phenotyping across two treatment lines. Methods/design In this exploratory prospective phase II clinical trial, newly diagnosed ALK+ NSCLC patients will be randomized into two treatment arms, stratified by presence of brain metastases and ECOG performance status: brigatinib (experimental arm) vs. any other approved second-generation ALK TKI. Tumor tissue and blood samples will be collected for biomarker analysis at the beginning and throughout the study period to investigate baseline molecular tumor properties and analyze the development of acquired drug resistance. In addition, participating investigators and patients will have the possibility of fast-track molecular tumor and ctDNA profiling at the time of disease progression using state-of-the-art next-generation sequencing (NGS), in order to support decisions regarding next-line therapy. Discussion Besides supporting therapeutic decisions for enrolled patients, the ABP trial primarily aims to deepen the understanding of the underlying biology and facilitate development of a framework for individualized management of ALK+ NSCLC according to molecular features. Patients with low molecular risk and the perspective of a “chronic disease” will be distinguished from “high-risk” cases, molecular properties of which will be utilized to elaborate improved methods of non-invasive monitoring and novel preclinical models in order to advance therapeutic strategies. Trial registration Clinicaltrials.gov, NCT04318938. Registered March 182,020, https://www.clinicaltrials.gov/ct2/show/NCT04318938 Eudra-CT, 2019–001828-36. Registered September 302,019, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-001828-36

scholarly journals Management and leadership: analysis of nurse manager's knowledge

2005 ◽  
Vol 13 (4) ◽  
pp. 469-473 ◽  
Author(s):  
Maria Regina Lourenço ◽  
Gilberto Tadeu Shinyashiki ◽  
Maria Auxiliadora Trevizan
Keyword(s):  
Nurse Managers ◽  
Care Center ◽  
Visionary Leadership ◽  
Nurse Manager ◽  
Team Work ◽  
Primary Care Center ◽  
Leadership Analysis ◽  
Leadership Management ◽  
Management Positions ◽  
Management And Leadership

Nurses have assumed management positions in many health institutions. To properly accomplish the demands of this role, it is important that they be competent in both management and leadership. For appropriate performance, knowledge of management and supervision styles is a priority. Therefore, the goal of this investigation is to identify the nurse manager's knowledge regarding management and leadership. A structured questionnaire containing twenty-seven questions was applied to twelve Brazilian nurse managers of primary care center called "Family Basic Health Units". Data analysis suggested that the nurse manager lower knowledge in management and leadership is related to visionary leadership, management and leadership conceptual differences, leader's behavior, and situational leadership. And, nurse manager greater knowledge is related to power; team work, and coherence between values and attitudes.

scholarly journals Identification of Novel Mutations Responsible for Resistance to MK-2048, a Second-Generation HIV-1 Integrase Inhibitor

2010 ◽  
Vol 84 (18) ◽  
pp. 9210-9216 ◽  
Author(s):  
Tamara Bar-Magen ◽  
Richard D. Sloan ◽  
Daniel A. Donahue ◽  
Björn D. Kuhl ◽  
Alexandra Zabeida ◽  
...  
Keyword(s):  
Viral Replication ◽  
First Generation ◽  
Second Generation ◽  
Integrase Inhibitor ◽  
Replication Capacity ◽  
Strand Transfer ◽  
Viral Replication Capacity ◽  
Transfer Inhibitor ◽  
Potential Basis

ABSTRACT MK-2048 represents a prototype second-generation integrase strand transfer inhibitor (INSTI) developed with the goal of retaining activity against viruses containing mutations associated with resistance to first-generation INSTIs, raltegravir (RAL) and elvitegravir (EVG). Here, we report the identification of mutations (G118R and E138K) which confer resistance to MK-2048 and not to RAL or EVG. These mutations were selected in vitro and confirmed by site-specific mutagenesis. G118R, which appeared first in cell culture, conferred low levels of resistance to MK-2048. G118R also reduced viral replication capacity to approximately 1% that of the isogenic wild-type (wt) virus. The subsequent selection of E138K partially restored replication capacity to ≈13% of wt levels and increased resistance to MK-2048 to ≈8-fold. Viruses containing G118R and E138K remained largely susceptible to both RAL and EVG, suggesting a unique interaction between this second-generation INSTI and the enzyme may be defined by these residues as a potential basis for the increased intrinsic affinity and longer “off” rate of MK-2048. In silico structural analysis suggests that the introduction of a positively charged arginine at position 118, near the catalytic amino acid 116, might decrease Mg2+ binding, compromising enzyme function and thus leading to the significant reduction in both integration and viral replication capacity observed with these mutations.

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