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https://www.readbyqxmd.com/read/28937991/sociodemographic-correlates-of-hiv-drug-resistance-and-access-to-drug-resistance-testing-in-british-columbia-canada
#1
Genevieve Rocheleau, Conrado Franco-Villalobos, Natalia Oliveira, Zabrina L Brumme, Melanie Rusch, Jeannie Shoveller, Chanson J Brumme, P Richard Harrigan
Sociodemographic correlates of engagement in human immunodeficiency virus (HIV) care are well studied, however the association with accessing drug resistance testing (DRT) and the development of drug resistance have not been characterized. Between 1996-2014, 11 801 HIV patients accessing therapy in British Columbia were observed longitudinally. A subset of 9456 patients had testable viral load; of these 8398 were linked to census data. Sociodemographic (census tract-level) and clinical (individual-level) correlates of DRT were assessed using multivariable General Estimating Equation logistic regression adjusted odds ratios (aOR)...
2017: PloS One
https://www.readbyqxmd.com/read/28934422/low-frequency-of-acquired-isoniazid-and-rifampicin-resistance-in-rifampicin-susceptible-pulmonary-tuberculosis-in-a-setting-of-high-hiv-1-infection-and-tuberculosis-coprevalence
#2
Neesha Rockwood, Frederick Sirgel, Elizabeth Streicher, Robin Warren, Graeme Meintjes, Robert J Wilkinson
Background: We estimated the incidence of acquired isoniazid and rifampicin resistance in rifampicin-susceptible tuberculosis in a setting of high human immunodeficiency virus type 1 (HIV-1) infection and tuberculosis coprevalence. Methods: GeneXpert MTB/RIF-confirmed patients with rifampicin-susceptible tuberculosis were recruited at antituberculosis treatment initiation in Khayelitsha, South Africa. Liquid culture and adherence assessment were performed at 2 and 5-6 months...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28926562/generics-for-the-treatment-of-hepatitis-c-in-monoinfected-and-hiv-coinfected-patients-pros-and-cons
#3
Dario Cattaneo, Alessandro Fossati, Chiara Resnati, Massimo Galli, Cristina Gervasoni
The treatment of hepatitis C virus in monoinfected and HIV-coinfected patients has greatly changed over recent years as a result of the introduction of direct-acting antiviral agents (DAAs), which have revolutionized clinical outcomes and led to sustained virological response rates above 90-95%. The discovery of new molecules and the subsequent competition between pharmaceutical companies, together with the negotiated price policies pursued by many national health systems, have led to a gradual reduction in the cost of DAAs, and expand their use to an increasing number of patients, including those with mild liver damage...
September 19, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28923862/antiviral-activity-of-bictegravir-and-cabotegravir-against-integrase-inhibitor-resistant-sivmac239-and-hiv-1
#4
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/28922979/a-review-of-drug-drug-interactions-in-older-hiv-infected-patients
#5
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/28919303/acquisition-of-wild-type-hiv-1-infection-in-a-patient-on-pre-exposure-prophylaxis-with-high-intracellular-concentrations-of-tenofovir-diphosphate-a-case-report
#6
Elske Hoornenborg, Maria Prins, Roel C A Achterbergh, Lycke R Woittiez, Marion Cornelissen, Suzanne Jurriaans, Neeltje A Kootstra, Peter L Anderson, Peter Reiss, Henry J C de Vries, Jan M Prins, Godelieve J de Bree
BACKGROUND: Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of HIV infection, and only two cases of infection with a multidrug-resistant virus have been reported under adequate long-term adherence, as evidenced by tenofovir diphosphate concentrations in dried blood spots. We report a case of wild-type HIV-1 infection despite consistent use of emtricitabine and tenofovir disoproxil fumarate. METHODS: The patient participated in the Amsterdam PrEP project, a demonstration project of daily and event-driven PrEP...
September 14, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28918303/decoding-noises-in-hiv-computational-genotyping
#7
MingRui Jia, Timothy Shaw, Xing Zhang, Dong Liu, Ye Shen, Amara E Ezeamama, Chunfu Yang, Ming Zhang
Lack of a consistent and reliable genotyping system can critically impede HIV genomic research on pathogenesis, fitness, virulence, drug resistance, and genomic-based healthcare and treatment. At present, mis-genotyping, i.e., background noises in molecular genotyping, and its impact on epidemic surveillance is unknown. For the first time, we present a comprehensive assessment of HIV genotyping quality. HIV sequence data were retrieved from worldwide published records, and subjected to a systematic genotyping assessment pipeline...
September 14, 2017: Virology
https://www.readbyqxmd.com/read/28915040/elucidating-the-interdependence-of-drug-resistance-from-combinations-of-mutations
#8
Debra A Ragland, Troy W Whitfield, Sook-Kyung Lee, Ronald Swanstrom, Konstantin B Zeldovich, Nese Kurt Yilmaz, Celia A Schiffer
HIV-1 protease is responsible for the cleavage of 12 non-homologous sites within the Gag and Gag-Pro-Pol polyproteins in the viral genome. Under the selective pressure of protease inhibition, the virus evolves mutations within (primary) and outside of (secondary) the active site allowing the protease to process substrates while simultaneously countering inhibition. The primary protease mutations impede inhibitor binding directly, while the secondary mutations are considered accessory mutations that compensate for a loss in fitness...
September 15, 2017: Journal of Chemical Theory and Computation
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
#9
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
#10
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
#11
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/28903800/predicting-treatment-failure-death-and-drug-resistance-using-a-computed-risk-score-among-newly-diagnosed-tb-patients-in-tamaulipas-mexico
#12
B E Abdelbary, M Garcia-Viveros, H Ramirez-Oropesa, M H Rahbar, B I Restrepo
The purpose of this study was to develop a method for identifying newly diagnosed tuberculosis (TB) patients at risk for TB adverse events in Tamaulipas, Mexico. Surveillance data between 2006 and 2013 (8431 subjects) was used to develop risk scores based on predictive modelling. The final models revealed that TB patients failing their treatment regimen were more likely to have at most a primary school education, multi-drug resistance (MDR)-TB, and few to moderate bacilli on acid-fast bacilli smear. TB patients who died were more likely to be older males with MDR-TB, HIV, malnutrition, and reporting excessive alcohol use...
September 14, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28900073/-molecular-mechanisms-of-hiv-1-genetic-diversity
#13
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/28899424/clade-homogeneity-and-low-rate-of-delta-virus-despite-hyperendemicity-of-hepatitis-b-virus-in-ethiopia
#14
Yeshambel Belyhun, Uwe Gerd Liebert, Melanie Maier
BACKGROUND: Although hepatitis B virus (HBV) is hyperendemic and heterogeneous in its genetic diversity in Ethiopia, little is known about hepatitis D virus (HDV) circulating genotypes and molecular diversity. METHODS: A total of 321 hepatitis B surface antigen (HBsAg) positives (125 HIV co-infected, 102 liver disease patients and 94 blood donors) were screened for anti-HDV antibody. The anti-HDV positive sera were subjected to Real time PCR for HDV-RNA confirmation...
September 12, 2017: Virology Journal
https://www.readbyqxmd.com/read/28899102/community-based-antiretroviral-treatment-in-rural-zimbabwe
#15
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
#16
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/28893790/combinatorial-crispr-cas9-and-rnai-attack-on-hiv-1-dna-and-rna-can-lead-to-cross-resistance
#17
Na Zhao, Gang Wang, Atze T Das, Ben Berkhout
Many potent antiviral drugs have been developed against HIV-1 and their combined action is usually successful in achieving durable virus suppression in infected individuals. This success is based on two effects: additive or even synergistic virus inhibition and an increase in the genetic threshold for development of drug-resistance. More recently, several genetic approaches have been developed to attack the HIV-1 genome in a gene therapy setting. We set out to test the combinatorial possibilities for a therapy based on the CRISPR-Cas9 and RNA interference (RNAi) mechanisms that attack the viral DNA and RNA, respectively...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28893361/colworth-prize-lecture-2016-exploiting-new-biological-targets-from-a-whole-cell-phenotypic-screening-campaign-for-tb-drug-discovery
#18
Patrick Joseph Moynihan, Gurdyal S Besra
Mycobacterium tuberculosis is the aetiological agent of tuberculosis (TB) and is the leading bacterial cause of mortality and morbidity in the world. One third of the world's population is infected with TB, and in conjunction with HIV represents a serious problem that urgently needs addressing. TB is a disease of poverty and mostly affects young adults in their productive years, primarily in the developing world. The most recent report from the World Health Organisation states that 8 million new cases of TB were reported and that ~1...
September 12, 2017: Microbiology
https://www.readbyqxmd.com/read/28893321/prevalence-and-trends-in-transmitted-and-acquired-antiretroviral-drug-resistance-washington-dc-1999-2014
#19
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/28893193/light-emitting-diode-fluorescent-microscopy-and-xpert-mtb-rif%C3%A2-assay-for-diagnosis-of-pulmonary-tuberculosis-among-patients-attending-ambo-hospital-west-central-ethiopia
#20
Alemu Gadissa Gelalcha, Abebaw Kebede, Hassen Mamo
BACKGROUND: The relatively simple and cheaper light-emitting diode fluorescent microscopy (LED-FM) was recommended by the World Health Organization (WHO) to replace the conventional tuberculosis (TB) microscopy in both high- and low-volume laboratories. More recently the WHO also endorsed one more technique, Xpert MTB/RIF® assay (Xpert), for improved TB diagnosis particularly among human immunodeficiency virus (HIV)-infected cases. However, the relative performance of both of these tools differs from setting to setting in reference to the conventional TB diagnostics...
September 11, 2017: BMC Infectious Diseases
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