scholarly journals Sustained HIV viral suppression with dolutegravir, tenofovir, and emtricitabine as initial therapy despite high-level transmitted multi-class resistance

2021 ◽  
Author(s):  
Ellen H Nagami ◽  
Kinna Thakarar ◽  
Paul E Sax
Keyword(s):  
Viral Suppression ◽  
Drug Class ◽  
Drug Regimen ◽  
Initial Therapy ◽  
Strand Transfer ◽  
Antiretroviral Drug ◽  
Integrase Strand Transfer Inhibitors ◽  
Hiv Viral Suppression ◽  
High Level ◽  
Selection Of

Abstract Multi-class high-level transmitted HIV drug resistance is uncommon, and the selection of the optimal initial antiretroviral drug regimen may be challenging. We report a case of extensive transmitted multi-class resistance successfully treated with dolutegravir, tenofovir, and emtricitabine even though the baseline genotype demonstrated full susceptibility to only one drug class, the integrase strand transfer inhibitors. Our case highlights both the high resistance barrier of dolutegravir and the residual antiviral activity of nucleoside reverse transcriptase inhibitors despite extensive resistance on genotype.

Impact of Integrase Strand Transfer Inhibitors use during Pregnancy on Viral Suppression at Delivery and Infant Outcomes

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
A. Hayden Latham ◽  
Oriel A. Nissim ◽  
Marjorie C. Spitznagel ◽  
Stephanie E. Kirk ◽  
Jessica L. Tarleton ◽  
...  
Keyword(s):  
Viral Suppression ◽  
Strand Transfer ◽  
Infant Outcomes ◽  
Integrase Strand Transfer Inhibitors

scholarly journals Association of Antiretroviral Drug Regimen With Viral Suppression in HIV-positive Children on Antiretroviral Therapy in Eswatini

2019 ◽  
Vol 38 (8) ◽  
pp. 835-839 ◽  
Author(s):  
Caspian Chouraya ◽  
Kim Ashburn ◽  
Philisiwe Khumalo ◽  
Lydia Mpango ◽  
Nobuhle Mthethwa ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Viral Suppression ◽  
Drug Regimen ◽  
Hiv Positive ◽  
Antiretroviral Drug

Antiretroviral drug reduction in highly experienced HIV-infected patients receiving a multidrug regimen: the ECOVIR study

2019 ◽  
Vol 74 (9) ◽  
pp. 2716-2722
Author(s):  
Marc-Antoine Valantin ◽  
Lise Durand ◽  
Marc Wirden ◽  
Lambert Assoumou ◽  
Fabienne Caby ◽  
...  
Keyword(s):  
Viral Suppression ◽  
Drug Regimen ◽  
Antiretroviral Drugs ◽  
Expert Advice ◽  
Resistance Mutations ◽  
Duration Of Treatment ◽  
Kaplan Meier ◽  
Virological Success ◽  
High Level ◽  
A Prospective Study

Abstract Objectives In a context of life-long therapy, we asked whether it could be possible to reduce the number of antiretroviral drugs without jeopardizing viral suppression. Methods ECOVIR was a prospective study aiming to assess whether in patients on combination ART with ≥4 antiretrovirals for ≥24 weeks and virally suppressed for ≥48 weeks, a drug-reduced (DR) regimen could be proposed. The intervention consisted of discontinuing genotypically less susceptible drugs to reach a DR regimen with ≤3 antiretrovirals. The primary endpoint was the proportion of patients maintaining viral suppression at week (W) 24. Results From 89 eligible individuals for the study, a DR regimen was proposed in 86 (97%) patients, of whom 71 were switched to a DR regimen. Baseline characteristics [median (IQR)] were: age 58 (53–65) years, duration of treatment 24 (21–26) years and viral suppression 8 (6–11) years. The cumulative resistance profile showed full resistance to lamivudine/emtricitabine (91%), abacavir (74%), efavirenz/nevirapine (70%), rilpivirine (56%), darunavir (q24h/q12h) (42%/29%), lopinavir (69%), atazanavir (71%) and raltegravir (24%). The final DR regimen consisted of a two-drug or three-drug regimen in 54 patients (76%) and in 17 patients (24%), respectively. The success rate of a DR regimen at W24 was 93.9% (95% CI 84.4–97.6, Kaplan–Meier estimate). Four patients experienced virological failure (at W4, W8 and W12), all with plasma viral load (pVL) <600 copies/mL and no emergence of resistance mutations. The DR strategy allowed a monthly cost saving of 36%. Conclusions In experienced patients with high-level resistance, individualized strategies based on expert advice can offer DR regimen options with fewer drug–drug interactions and a significant economic impact while ensuring virological success.

scholarly journals Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir

2018 ◽  
Vol 5 (10) ◽  
Author(s):  
Jomy M George ◽  
Safia S Kuriakose ◽  
Nicola Dee ◽  
Pam Stoll ◽  
Tahaniyat Lalani ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Rapid Development ◽  
Fold Increase ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Integrase Strand Transfer Inhibitors ◽  
Single Addition ◽  
High Level ◽  
Level Resistance

Abstract HIV integrase mutation T97A emerges after suboptimal therapy with integrase strand transfer inhibitors (INSTIs), but the contribution of T97A to dolutegravir resistance remains uncertain. Here we report &gt;10-fold increase in dolutegravir resistance after the single addition of T97A in 2 individuals with prior INSTI resistance receiving dolutegravir salvage therapy.

SBA MCQs for the MRCS Part A

2012 ◽  
Author(s):  
Sri G. Thrumurthy ◽  
Tania Samantha De Silva ◽  
Zia Moinuddin ◽  
Stuart Enoch
Keyword(s):  
Clinical Case ◽  
Multiple Choice ◽  
Surgical Anatomy ◽  
Surgical Patients ◽  
Multiple Choice Questions ◽  
Basic Sciences ◽  
Self Assessment ◽  
High Level ◽  
Factual Recall ◽  
Selection Of

Specifically designed to help candidates revise for the MRCS exam, this book features 350 Single Best Answer multiple choice questions, covering the whole syllabus. Containing everything candidates need to pass the MRCS Part A SBA section of the exam, it focuses intensively on the application of basic sciences (applied surgical anatomy, physiology, and pathology) to the management of surgical patients. The high level of detail included within the questions and their explanations allows effective self-assessment of knowledge and quick identification of key areas requiring further attention. Varying approaches to Single Best Answer multiple choice questions are used, giving effective exam practice and guidance through revision and exam technique. This includes clinical case questions, 'positively-worded' questions, requiring selection of the most appropriate of relatively correct answers; 'two-step' or 'double-jump' questions, requiring several cognitive steps to arrive at the correct answer; as well as 'factual recall' questions, prompting basic recall of facts.

Lower perception of pharmacological treatment increases risk of non-adherence to medication

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
CB Graversen ◽  
JB Valentin ◽  
ML Larsen ◽  
S Riahi ◽  
T Holmberg ◽  
...  
Keyword(s):  
Pharmacological Treatment ◽  
Poisson Regression ◽  
Drug Class ◽  
Angiotensin Receptor Blockers ◽  
Adverse Outcomes ◽  
Adherence To Medication ◽  
Increased Risk ◽  
Patient Reported ◽  
High Level

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Background A large proportion of patients fail to reach optimal adherence to medication following incident ischemic heart disease (IHD) despite amble evidence of the beneficial effect of medication. Non-adherence to medication increases risk of disease-related adverse outcomes but none has explored how perception about pharmacological treatment detail on non-adherence using register-based follow-up data. Purpose To investigate the association between patients’ perception of pharmacological treatment and risk of non-initiation and non-adherence to medication in a population with incident IHD. Methods This cohort study followed 871 patients until 365 days after incident IHD. The study combined patient-reported survey data on perception about pharmacological treatment (categorised by ‘To a high level’, ‘To some level’, and ‘To a lesser level’) with register-based data on reimbursed prescription of cardiovascular medication (antithrombotics, statins, ACE-inhibitors/angiotensin receptor blockers, and β-blockers). Non-initiation was defined as no pick-up of medication in the first 180 days following incident IHD and analysed by Poisson regression. Two different measures evaluated non-adherence in patients initiating treatment: 1) proportion of days covered (PDC) analysed by Poisson regression, and 2) risk of discontinuation analysed by Cox proportional hazard regression. All analyses were adjusted for confounding variables (age, sex, ethnicity, income, educational level, civil status, occupation, charlson comorbidity index, supportive relatives, and individual consultation in medication) identified by directed acyclic graph and obtained from national registers and the survey. Item non-response was handled by multiple imputation and item consistency was evaluated by McDonalds omega. Results Lower perceptions about pharmacological treatment was associated with increased risk of non-initiation and non-adherence to medication irrespectively of drug class and adherence measure in the multiple adjusted analyses (please see figure illustrating results on antithrombotics). A dose-response relationship was observed both at 180- and 365-days of follow-up, but the steepest decline in adherence differed when comparing the two adherence measures (results not shown). Moderate internal consistency was found for the summed measure of perception (McDonalds omega = 0.67). Conclusion Lower perception of pharmacological treatment was associated with subsequent non-initiation and non-adherence to medication, irrespectively of measurement method and drug class. Abstract Figure. Figre: Multiple adjusted analyses

Inflammatory Myositis Secondary to Anti-Retroviral Therapy in a Child; Case Report and Review of the Literature

2021 ◽  
pp. 1-7
Author(s):  
Marie Monaghan ◽  
Charlotte Loh ◽  
Stephen Jones ◽  
Agyepong Oware ◽  
Kathryn Urankar ◽  
...  
Keyword(s):  
Drug Regimen ◽  
Dramatic Improvement ◽  
Strand Transfer ◽  
Inflammatory Myositis ◽  
Once Daily ◽  
Immune Mediated ◽  
Show Evidence ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Here, we describe a five year old girl with congenital HIV who had a six-week onset of rapidly deteriorating mobility and progressive proximal muscle weakness, associated with a raised Creatine Kinase (CK) level of 4330 U/L [25–200 U/L], subsequently diagnosed with an inflammatory myositis. Potential causes were investigated by paediatric neurology and immunology teams. Her viral load had been undetectable over the preceding two years, excluding a primary HIV myositis. While MRI scanning did not show evidence of definite myositis, a muscle biopsy showed evidence of an inflammatory process, comprising a moderate endomysial, perimysial and perivascular mononuclear (CD8 + T cell) infiltrate with increased MHC expression. No particular features of dermatomyositis or immune-mediated necrotising myopathy were identified and there were no features of an inclusion body myositis. Given the absence of active HIV infection, the role of anti-retroviral medications was considered. She had had a recent switch in medication, from twice daily Raltegravir (an Integrase Strand Transfer Inhibitor, INSTI) to once daily Dolutegravir (an INSTI) while continuing on an established daily protocol of Abacavir and Lamivudine (Nucleoside Reverse Transcriptase Inhibitors). Changing the Dolutegravir back to Raltegravir, in combination with continuing Lamivudine and Abacavir for two months made no difference to her weakness or CK levels. Moreover, this drug regimen had been well-tolerated over the preceding 19 month period. Changing the anti-retroviral regime completely to a single drug class (Protease Inhibitors) of Ritonavir and Darunavir, resulted in a dramatic improvement in her symptomatology. Within ten days she regained the ability to stand and walk, with a reduction in her CK from 1700 U/L at time of switch to 403 U/L [25–200]. This case highlights the potential risk of developing inflammatory myositis from anti-retrovirals even 19 months into treatment.

scholarly journals Photodynamic Therapy Combined with Antibiotics or Antifungals against Microorganisms That Cause Skin and Soft Tissue Infections: A Planktonic and Biofilm Approach to Overcome Resistances

2021 ◽  
Vol 14 (7) ◽  
pp. 603
Author(s):  
Vanesa Pérez-Laguna ◽  
Isabel García-Luque ◽  
Sofía Ballesta ◽  
Antonio Rezusta ◽  
Yolanda Gilaberte
Keyword(s):  
Photodynamic Therapy ◽  
Soft Tissues ◽  
Combined Treatment ◽  
Resistance Pattern ◽  
Antimicrobial Photodynamic Therapy ◽  
Antimicrobial Drugs ◽  
Bacteria And Fungi ◽  
High Level ◽  
Selection Of

The present review covers combination approaches of antimicrobial photodynamic therapy (aPDT) plus antibiotics or antifungals to attack bacteria and fungi in vitro (both planktonic and biofilm forms) focused on those microorganisms that cause infections in skin and soft tissues. The combination can prevent failure in the fight against these microorganisms: antimicrobial drugs can increase the susceptibility of microorganisms to aPDT and prevent the possibility of regrowth of those that were not inactivated during the irradiation; meanwhile, aPDT is effective regardless of the resistance pattern of the strain and their use does not contribute to the selection of antimicrobial resistance. Additive or synergistic antimicrobial effects in vitro are evaluated and the best combinations are presented. The use of combined treatment of aPDT with antimicrobials could help overcome the difficulty of fighting high level of resistance microorganisms and, as it is a multi-target approach, it could make the selection of resistant microorganisms more difficult.

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