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https://www.readbyqxmd.com/read/28923862/antiviral-activity-of-bictegravir-and-cabotegravir-against-integrase-inhibitor-resistant-sivmac239-and-hiv-1
#1
Said A Hassounah, Ahmad Alikhani, Maureen Oliveira, Simrat Bharaj, Ruxandra-Ilinca Ibanescu, Nathan Osman, Hong-Tao Xu, Bluma G Brenner, Thibault Mesplède, Mark A Wainberg
Animal models are essential to study novel antiretroviral drugs, resistance-associated mutations (RAMs), and treatment strategies. Bictegravir (BIC) is a novel potent integrase (IN) strand transfer inhibitor (INSTI) that has shown promising results against HIV-1 infection in vitro and in vivo and against clinical isolates with resistance against INSTIs. BIC has a higher genetic barrier to the development of resistance than two clinically approved INSTIs termed raltegravir and elvitegravir. Another clinically approved INSTI, dolutegravir (DTG) also possesses a high genetic barrier to resistance while a fourth compound termed cabotegravir (CAB) is currently in late phases of clinical development...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28923179/drugs-and-hyperglycemia-a-practical-guide
#2
REVIEW
Vandana Jain, Ronak Kumar Patel, Zaureen Kapadia, Sneha Galiveeti, Maryann Banerji, Lisel Hope
Drug-induced diabetes is one of the factors contributing to the increasing incidence of diabetes worldwide. This review considers the frequency, pathogenesis and treatment of drug-induced diabetes. Drugs that induce diabetes include hormonal therapy, especially glucocorticoids and androgen blockers, cardiovascular drugs, especially statins, beta-blockers and diuretics, antipsychotics, especially clozapine, olanzapine and quetiapine, antiretrovirals (protease inhibitors and non-reverse transcriptase inhibitors - NRTIs) and other drugs (mechanistic target of rapamycin inhibitors -mTORs, post organ transplantation drugs, tyrosine kinase inhibitors and interferon-alpha)...
October 2017: Maturitas
https://www.readbyqxmd.com/read/28922979/a-review-of-drug-drug-interactions-in-older-hiv-infected-patients
#3
Aarthi Chary, Nancy N Nguyen, Kimberly Maiton, Mark Holodniy
The number of older HIV-infected people is growing due to increasing life expectancies resulting from the use of antiretroviral therapy (ART). Both HIV and aging increase the risk of other comorbidities, such as cardiovascular disease, osteoporosis, and some malignancies, leading to greater challenges in managing HIV with other conditions. This results in complex medication regimens with the potential for significant drug-drug interactions and increased morbidity and mortality. Area covered: We review the metabolic pathways of ART and other medications used to treat medical co-morbidities, highlight potential areas of concern for drug-drug interactions, and where feasible, suggest alternative approaches for treating these conditions as suggested from national guidelines or articles published in the English language...
September 19, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28919833/conventional-culture-versus-nucleic-acid-amplification-tests-for-screening-of-urethral-neisseria-gonorrhea-infection-among-asymptomatic-men-who-have-sex-with-men
#4
Jiratha Budkaew, Bandit Chumworathayi, Chamsai Pientong, Tipaya Ekalaksananan
BACKGROUND: Many methods are used to detect urethral Neisseria gonorrhea (NG) infection among asymptomatic men who have sex with men (MSM). The objective of this study was to define the performance of conventional culture compared to real-time polymerase chain reaction (PCR) for diagnosis of asymptomatic urethral gonorrhea among MSM. METHODS: In this cross-sectional study, 147 clinical specimens for NG testing from asymptomatic participants were evaluated. MSM >18 years old who consented to undergo urethral swab and collection of urine samples from two clinics (one was the sexually transmitted diseases (STDs) mobile clinic and the second was the antiretroviral clinic) located in Khon Kaen, Thailand, were recruited...
2017: Pragmatic and Observational Research
https://www.readbyqxmd.com/read/28919720/text-messaging-to-decrease-tuberculosis-treatment-attrition-in-tb-hiv-coinfection-in-uganda
#5
Sabine M Hermans, Sawsan Elbireer, Harriet Tibakabikoba, Bas J Hoefman, Yukari C Manabe
BACKGROUND: Low tuberculosis (TB) treatment completion rates in sub-Saharan Africa are an important driver of multidrug resistance. Mobile technology-based interventions have been shown to improve adherence to antiretroviral therapy in sub-Saharan Africa. We aimed to test the effect of a short-message service (SMS) intervention on loss to follow-up (LFU). MATERIALS AND METHODS: In this quasi-experimental study, all adult, literate, HIV-infected patients with mobile phone access diagnosed with TB between November 2010 and October 2011 in an urban clinic in Uganda were eligible to receive adherence and appointment reminders and educational quizzes during the first 8 weeks of TB treatment...
2017: Patient Preference and Adherence
https://www.readbyqxmd.com/read/28914169/development-of-an-algorithm-for-determination-of-the-likelihood-of-virological-failure-in-hiv-positive-adults-receiving-antiretroviral-therapy-in-decentralized-care
#6
Anton Reepalu, Taye Tolera Balcha, Sten Skogmar, Per-Erik Isberg, Patrik Medstrand, Per Björkman
BACKGROUND: Early identification of virological failure (VF) limits occurrence and spread of drug-resistant viruses in patients receiving antiretroviral treatment (ART). Viral load (VL) monitoring is therefore recommended, but capacities to comply with this are insufficient in many low-income countries. Clinical algorithms might identify persons at higher likelihood of VF to allocate VL resources. OBJECTIVES: We aimed to construct a VF algorithm (the Viral Load Testing Criteria; VLTC) and compare its performance to the 2013 WHO treatment failure criteria...
2017: Global Health Action
https://www.readbyqxmd.com/read/28911353/persistently-high-early-mortality-despite-rapid-diagnostics-for-drug-resistant-tuberculosis-cases-in-south-africa
#7
K Schnippel, C Firnhaber, N Ndjeka, F Conradie, L Page-Shipp, R Berhanu, E Sinanovic
OBJECTIVE: To describe the timing and predictors of mortality among multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) patients reported in the South African electronic drug-resistant TB register (EDRweb), 2012-2014. DESIGN: We present time-to-event survival analysis and Cox proportional hazards regression. Identity numbers were matched to the National Vital Statistics Register. RESULTS: Of the 20 653 patients included in the analysis (median age 35 years, interquartile range 28-43), over half were male (n = 10 944, 53...
October 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28904329/latest-advances-in-the-efficacy-tolerability-and-monotherapy-of-integrase-inhibitors
#8
Qi Tang, Hongzhou Lu
More than 30 drugs for antiretroviral therapy (ART), including integrase inhibitors (INIs), have been approved by the U.S. Food and Drug Administration (FDA) as of 2017. Integrase is the third essential enzyme in the cycle of human immunodeficiency virus (HIV) replication. INIs can effectively inhibit the replication of HIV and HIV is less prone to develop resistance to INIs clinically. Previous studies based on 7 phase III clinic trials indicate that INIs have satisfactory efficacy and tolerability in patients infected with HIV...
2017: Bioscience Trends
https://www.readbyqxmd.com/read/28903730/routine-monitoring-and-assessment-of-adults-living-with-hiv-results-of-the-british-hiv-association-bhiva-national-audit-2015
#9
A Molloy, H Curtis, F Burns, A Freedman
BACKGROUND: The clinical care of people living with HIV changed fundamentally as a result of the development of effective antiretroviral therapy (ART). HIV infection is now a long-term treatable condition. We report a national audit to assess adherence to British HIV Association guidelines for the routine investigation and monitoring of adult HIV-1-infected individuals. METHODS: All UK sites known as providers of adult HIV outpatient services were invited to complete a case-note review and a brief survey of local clinic practices...
September 13, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28900073/-molecular-mechanisms-of-hiv-1-genetic-diversity
#10
D V Sosin, N A Tchurikov
High genetic diversity of HIV-1 is the main factor behind the fact that HIV infection is widespread and difficult to treat. Although a limited number (or only one) of virus particles enters the blood upon infection, the particles are replicated in infected cells and rapidly produce new genetic variants that are resistant to the host immune system and antiretroviral drugs. This circumstance hampers the development of anti-HIV-1 vaccines and requires new antiretroviral drugs to be designed. The cause of the high variation of HIV-1 is related to the properties of its reverse transcriptase, which is error prone and often makes mistakes when transcribing virus RNA...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28899102/community-based-antiretroviral-treatment-in-rural-zimbabwe
#11
Benjamin Chimukangara, Justen Manasa, Rebecca Mitchell, Georgina Nyabadza, David Katzenstein, Collen Masimirembwa
INTRODUCTION: Treatment of HIV has reduced HIV/AIDS-related mortality. Sustaining >90% virologic suppression in sub-Saharan Africa requires decentralized care and prevention services to rural communities. In Zimbabwe, the number of people receiving ART has increased rapidly. However, access to treatment monitoring tools such as viral load and drug resistance testing is limited. We assessed virologic treatment outcomes among ART recipients in Nyamutora, a rural community receiving bimonthly ART and prevention services...
September 13, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28893794/effects-of-hiv-1-tat-and-methamphetamine-on-blood-brain-barrier-integrity-and-function-in-vitro
#12
Sulay Patel, Crystal R Leibrand, Preetha Palasuberniam, Pierre-Olivier Couraud, Babette Weksler, Fay M Jahr, Joseph L McClay, Kurt F Hauser, MaryPeace McRae
Human immunodeficiency (HIV) infection results in neurocognitive deficits in about one half of infected individuals. Despite systemic effectiveness, restricted antiretroviral penetration across the blood-brain barrier (BBB) is a major limitation in fighting CNS-localized infection. Drug abuse exacerbates HIV-induced cognitive and pathologic CNS changes. This study's purpose was to investigate the effects of the HIV-1 protein, Tat, and methamphetamine on factors affecting drug penetration across an in vitro BBB model...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28893672/a-situational-analysis-of-current-antimicrobial-governance-regulation-and-utilisation-in-south-africa
#13
Natalie Schellack, Deon Benjamin, Adrian Brink, Adriano Duse, Kim Faure, Debra Goff, Marc Mendelson, Johanna Meyer, Jacqui Miot, Olga Perovic, Troy Pople, Fatima Suleman, Moritza van Vuuren, Sabiha Essack
The Global Action Plan (GAP) on AMR calls for optimising the use of antimicrobial medicines in human and animal health, in tandem with strengthening of the knowledge and evidence base through surveillance and research. However, there is a paucity of consumption data in African countries such as South Africa. Determining antimicrobial consumption data in low resource settings remains a challenge. This paper describes alternative mechanisms of assessing antimicrobial consumption data such as Intercontinental Marketing Services (IMS), and contract data arising from tenders (an open Request for Proposal, RFP) as opposed to the international norms of daily defined doses per 100 patient days, or per 1000 of the population...
September 8, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28893321/prevalence-and-trends-in-transmitted-and-acquired-antiretroviral-drug-resistance-washington-dc-1999-2014
#14
Annette M Aldous, Amanda D Castel, David M Parenti
BACKGROUND: Drug resistance limits options for antiretroviral therapy (ART) and results in poorer health outcomes among HIV-infected persons. We sought to characterize resistance patterns and to identify predictors of resistance in Washington, DC. METHODS: We analyzed resistance in the DC Cohort, a longitudinal study of HIV-infected persons in care in Washington, DC. We measured cumulative drug resistance (CDR) among participants with any genotype between 1999 and 2014 (n = 3411), transmitted drug resistance (TDR) in ART-naïve persons (n = 1503), and acquired drug resistance (ADR) in persons with genotypes before and after ART initiation (n = 309)...
September 11, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28886044/genetic-variants-in-cyp2b6-and-cyp2a6-explain-interindividual-variation-in-efavirenz-plasma-concentrations-of-hiv-infected-children-with-diverse-ethnic-origin
#15
Sandra Soeria-Atmadja, Emma Österberg, Lars L Gustafsson, Marja-Liisa Dahl, Jaran Eriksen, Johanna Rubin, Lars Navér
BACKGROUND: Approximately 2.6 million children live with HIV globally, and efavirenz (EFV) is one of the most widely used antiretroviral agents for HIV treatment in children and adults. There are concerns about the appropriateness of current EFV dosing and it has been discussed whether EFV dosing should be adapted according to genotype in children as suggested for adults. AIM: To investigate if pediatric EFV dosing should be guided by genetic variation in drug metabolizing enzymes rather than by body weight...
2017: PloS One
https://www.readbyqxmd.com/read/28882911/predictors-of-hiv-virological-failure-and-drug-resistance-in-chinese-patients-after-48-months-of-antiretroviral-treatment-2008-2012-a-prospective-cohort-study
#16
Wei Kan, Tao Teng, Shujia Liang, Yanling Ma, Heng Tang, Tuerdi Zuohela, Guoqing Sun, Cui He, Kristin M Wall, Vincent C Marconi, Lingjie Liao, Xuebing Leng, Pengtao Liu, Yuhua Ruan, Hui Xing, Yiming Shao
OBJECTIVE: To explore factors associated with HIV virological failure (VF) and HIV drug resistance (HIVDR) among HIV-positive Chinese individuals 4 years after initiating first-line lamivudine-based antiretroviral treatment (ART) in 2008 at five sentinel sites. DESIGN: First-line ART initiators who were previously treatment naïve were selected using consecutive ID numbers from the 2008 National Surveillance Database into a prospective cohort study. Questionnaires and blood samples were collected in 2011 and 2012 to assess the outcomes of interest: VF (defined as viral load ≥1000 copies/mL) and HIVDR (defined as VF with genetic drug-resistant mutations)...
September 7, 2017: BMJ Open
https://www.readbyqxmd.com/read/28879787/moving-forward-with-treatment-options-for-hiv-infected-children
#17
Jean-Christophe Beghin, Jean Cyr Yombi, Jean Ruelle, Dimitri Van der Linden
Current international guidelines recommend to treat all HIV-1 infected patients regardless of CD4 cell count. Despite the remarkable worldwide progress for universal access to antiretroviral during the last decade, the pediatric population remains fragile due to lack of randomized studies, inappropriate antiretroviral formulations, adherence difficulties, drug toxicity and development of resistance. Areas covered: This review summarizes the latest recommendations and advances for the treatment of HIV-infected children and highlights the potential complications of a lifelong antiretroviral treatment initiated early in life...
September 7, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28870148/accumulation-of-hiv-1-drug-resistance-in-patients-on-a-standard-thymidine-analogue-based-first-line-antiretroviral-therapy-after-virological-failure-implications-for-the-activity-of-next-line-regimens-from-a-longitudinal-study-in-mozambique
#18
Andrea De Luca, Zita Jorge Sidumo, Giacomo Zanelli, Noorjehan Abdul Magid, Richard Luhanga, Davide Brambilla, Giuseppe Liotta, Sandro Mancinelli, Maria Cristina Marazzi, Leonardo Palombi, Susanna Ceffa
BACKGROUND: We describe the accumulation of HIV-1 drug resistance and its effect on the activity of next-line components in patients with virological failure (HIV-1 RNA >1000 copies/mL) after 1 year (t1) of first-line antiretroviral therapy (ART) not switching to second-line drugs for one additional year (t2) in low-middle income countries (LMIC). METHODS AND RESULTS: We selected 48 patients from the DREAM cohort (Maputo, Mozambique); their median pre-ART CD4+ cell count was 165 cells/μl...
September 5, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28867497/bictegravir-emtricitabine-and-tenofovir-alafenamide-versus-dolutegravir-abacavir-and-lamivudine-for-initial-treatment-of-hiv-1-infection-gs-us-380-1489-a-double-blind-multicentre-phase-3-randomised-controlled-non-inferiority-trial
#19
Joel Gallant, Adriano Lazzarin, Anthony Mills, Chloe Orkin, Daniel Podzamczer, Pablo Tebas, Pierre-Marie Girard, Indira Brar, Eric S Daar, David Wohl, Jürgen Rockstroh, Xuelian Wei, Joseph Custodio, Kirsten White, Hal Martin, Andrew Cheng, Erin Quirk
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended components of initial antiretroviral therapy with two nucleoside reverse transcriptase inhibitors. Bictegravir is a novel, potent INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug-drug interactions. We aimed to assess the efficacy and safety of bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination versus coformulated dolutegravir, abacavir, and lamivudine...
August 31, 2017: Lancet
https://www.readbyqxmd.com/read/28865281/design-strategies-in-the-prodrugs-of-hiv-1-protease-inhibitors-to-improve-the-pharmaceutical-properties
#20
REVIEW
Murugaiah A M Subbaiah, Nicholas A Meanwell, John F Kadow
Combination antiretroviral therapy (cART) is currently the most effective treatment for HIV-1 infection. HIV-1 protease inhibitors (PIs) are an important component of some regimens of cART. However, PIs are known for sub-optimal ADME properties, resulting in poor oral bioavailability. This often necessitates high drug doses, combination with pharmacokinetic enhancers and/or special formulations in order to effectively deliver PIs, which may lead to a high pill burden and reduced patient compliance. As a remedy, improving the ADME properties of existing drugs via prodrug and other approaches has been pursued in addition to the development of next generation PIs with improved pharmacokinetic, resistance and side effect profiles...
July 22, 2017: European Journal of Medicinal Chemistry
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