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https://www.readbyqxmd.com/read/29329318/erythrocyte-inosine-triphosphatase-activity-a-potential-biomarker-for-adverse-events-during-combination-antiretroviral-therapy-for-hiv
#1
N Chantal Peltenburg, Jörgen Bierau, Jaap A Bakker, Jolanda A Schippers, Selwyn H Lowe, Aimée D C Paulussen, Bianca J C van den Bosch, Mathie P G Leers, Bettina E Hansen, Annelies Verbon
The purine analogues tenofovir and abacavir are precursors of potential substrates for the enzyme Inosine 5'-triphosphate pyrophosphohydrolase (ITPase). Here, we investigated the association of ITPase activity and ITPA genotype with the occurrence of adverse events (AEs) during combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV-seropositive patients, AEs were defined as events that led to stop of cART regimen. ITPase activity ≥4 mmol IMP/mmol Hb/hour was considered as normal...
2018: PloS One
https://www.readbyqxmd.com/read/29319822/an-animal-model-of-abacavir-induced-hla-mediated-liver-injury
#2
Binbin Song, Shigeki Aoki, Cong Liu, Takeshi Susukida, Kousei Ito
Genome-wide association studies indicate that several idiosyncratic adverse drug reactions are highly associated with specific human leukocyte antigen (HLA) alleles. For instance, abacavir, a human immunodeficiency virus reverse transcriptase inhibitor, induces multi-organ toxicity exclusively in patients carrying the HLA-B*57:01 allele. However, the underlying mechanism is unclear due to a lack of appropriate animal models. Previously, we developed HLA-B*57:01 transgenic mice and found that topical application of abacavir to the ears induced proliferation of CD8+ lymphocytes in local lymph nodes...
January 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29318459/incidence-and-predictors-of-single-drug-discontinuation-according-to-the-presence-of-hcv-coinfection-in-hiv-patients-from-the-icona-foundation-cohort-study
#3
Sebastiano Leone, Milensu Shanyinde, Alessandro Cozzi Lepri, Fiona C Lampe, Pietro Caramello, Andrea Costantini, Andrea Giacometti, Andrea De Luca, Antonella Cingolani, Francesca Ceccherini Silberstein, Massimo Puoti, Andrea Gori, Antonella d'Arminio Monforte
To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation...
January 9, 2018: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/29242412/hla-b-5701-allele-in-hiv-infected-indian-children-and-its-association-with-abacavir-hypersensitivity
#4
Mamta V Manglani, Yashwant R Gabhale, Mamatha M Lala, Rohini Sekhar, Dipti More
OBJECTIVE: To determine the prevalence of HLA-B*5701 allele in HIV-infected children, and to find its association with Abacavir hypersensitivity. METHODS: Children (2 to 18 y) already on, or to be initiated on Abacavir were included for PCR sequencing to detect HLA-B*5701. Outcome measures included prevalence of the HLA B*5701 allele and hypersensitivity with Abacavir. Abacavir was stopped if patient tested positive for HLA-B*5701 allele. RESULTS: 100 children (median age 11 y) were enrolled; 10 were already on Abacavir...
December 14, 2017: Indian Pediatrics
https://www.readbyqxmd.com/read/29227461/population-pharmacokinetics-of-lopinavir-in-severely-malnourished-hiv-infected-children-and-the-effect-on-treatment-outcomes
#5
Moherndran Archary, Helen Mcllleron, Raziya Bobat, Phillip La Russa, Thobekile Sibaya, Lubbe Wiesner, Stefanie Hennig
BACKGROUND: In developing countries, malnutrition remains a common clinical syndrome at antiretroviral treatment (ART) initiation. Physiological changes due to malnutrition and during nutritional recovery could affect the pharmacokinetics of antiretroviral drugs. METHODS: HIV-infected children admitted with severe acute malnutrition were randomised to early or delayed initiation of lopinavir/ritonavir, abacavir and lamivudine using WHO weight-band dosage charts...
December 8, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29210336/simplification-to-dual-therapy-containing-lamivudine-and-darunavir-ritonavir-or-atazanavir-ritonavir-in-hiv-infected-patients-on-virologically-suppressive-antiretroviral-therapy
#6
Leonardo Calza, Matteo Cafaggi, Vincenzo Colangeli, Marco Borderi, Enrico Barchi, Massimiliano Lanzafame, Stefano Nicole', Anna Maria Degli Antoni, Isabella Bon, Maria Carla Re, Pierluigi Viale
BACKGROUND: The ritonavir-boosted protease inhibitor (PI/r)-based dual regimens are warranted in order to optimize the combination antiretroviral therapy (cART), prevent the long-term toxicity and reduce the cost of treatments. METHODS: We performed an observational, retrospective study of HIV-infected patients on suppressive antiretroviral therapy who switched to a dual regimen containing lamivudine (3TC) plus darunavir/ritonavir (DRV/r) 800/100 mg qd or atazanavir/ritonavir (ATV/r) 300/100 mg qd...
December 6, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/29195713/generic-antiretroviral-drug-use-in-hiv-infected-patients-a-cohort-study-from-the-french-health-insurance-database
#7
Joseph Rwagitinywa, Maryse Lapeyre-Mestre, Robert Bourrel, Agnès Sommet
OBJECTIVE: This study aimed to estimate the rate of generic users among HIV-infected patients treated by antiretroviral (ARV) drugs potentially substitutable and to determine factors associated with switch from brand to generic ARV in real-life settings in a French region. METHODS: Cohort of HIV-infected patients aged of ≥18 years, exposed to at least one of the generic of lamivudine (3TC-150mg/300mg), zidovudine/lamivudine (AZT-200mg/3TC-150mg), nevirapine (NVP-200mg), efavirenz (EFV-600mg) and those exposed to brand 3TC, AZT/3TC, NVP, EFV, the fixed-dose combination abacavir/lamivudine (ABC/3TC) or the single-tablet regimen efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF) as recorded in the French health insurance database between January 2012 and May 2015 were included...
November 2, 2017: Thérapie
https://www.readbyqxmd.com/read/29177645/ledipasvir-sofosbuvir-for-8%C3%A2-weeks-in-non-cirrhotic-patients-with-previously-untreated-genotype-1-hcv-infection%C3%A2-%C3%A2-%C3%A2-hiv-1-co-infection
#8
Vasily Isakov, Natalia Gankina, Viacheslav Morozov, Kathryn Kersey, Sophia Lu, Anu Osinusi, Evguenia Svarovskaia, Diana M Brainard, Riina Salupere, Elena Orlova-Morozova, Konstantin Zhdanov
BACKGROUND AND OBJECTIVES: The efficacy of < 12 weeks of hepatitis C virus (HCV) treatment in patients co-infected with HCV and human immunodeficiency virus type 1 (HIV-1) has not been established. We assessed the efficacy and safety of ledipasvir-sofosbuvir for 8 weeks in HCV mono-infected and HCV/HIV-1 co-infected patients. METHODS: We enrolled patients mono-infected with genotype 1 HCV or co-infected with HCV and HIV-1 who were HCV treatment-naive and did not have cirrhosis...
November 24, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29171940/human-leukocyte-antigens-key-regulators-of-t-cell-mediated-drug-hypersensitivity
#9
REVIEW
A J Redwood, R K Pavlos, K D White, E J Phillips
Adverse drug reactions (ADR) can be broadly categorised as either on-target or off-target. On-target ADRs arise as a direct consequence of the pharmacological properties of the drug and are therefore predictable and dose dependant. On-target ADRs comprise the majority (>80%) of ADRs, relate to the drug's interaction with its known pharmacological target and are a result of a complex interplay of genetic and ecologic factors. In contrast off-target ADRs, including immune mediated ADRs (IM-ADRs), are due to unintended pharmacological interactions such as inadvertent ligation of host cell receptors or non-pharmacological interactions mediated through an adaptive immune response...
November 24, 2017: HLA
https://www.readbyqxmd.com/read/29150704/evaluation-of-immune-mediated-idiosyncratic-drug-toxicity-using-chimeric-hla-transgenic-mice
#10
Takeshi Susukida, Shigeki Aoki, Kotaro Kogo, Sota Fujimori, Binbin Song, Cong Liu, Shuichi Sekine, Kousei Ito
Immune-mediated idiosyncratic drug toxicity (IDT) is a rare adverse drug reaction, potentially resulting in death. Although genome-wide association studies suggest that the occurrence of immune-mediated IDT is strongly associated with specific human leukocyte antigen (HLA) allotypes, these associations have not yet been prospectively demonstrated. In this study, we focused on HLA-B*57:01 and abacavir (ABC)-induced immune-mediated IDT, and constructed transgenic mice carrying chimeric HLA-B*57:01 (B*57:01-Tg) to determine if this in vivo model may be useful for evaluating immune-mediated IDT...
November 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29136032/virological-response-and-resistance-among-hiv-infected-children-receiving-long-term-antiretroviral-therapy-without-virological-monitoring-in-uganda-and-zimbabwe-observational-analyses-within-the-randomised-arrow-trial
#11
Alexander J Szubert, Andrew J Prendergast, Moira J Spyer, Victor Musiime, Philippa Musoke, Mutsa Bwakura-Dangarembizi, Patricia Nahirya-Ntege, Margaret J Thomason, Emmanuel Ndashimye, Immaculate Nkanya, Oscar Senfuma, Boniface Mudenge, Nigel Klein, Diana M Gibb, A Sarah Walker
BACKGROUND: Although WHO recommends viral load (VL) monitoring for those on antiretroviral therapy (ART), availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring. METHODS AND FINDINGS: In the ARROW factorial trial, 1,206 children initiating ART in Uganda and Zimbabwe between 15 March 2007 and 18 November 2008, aged a median 6 years old, with median CD4% of 12%, were randomised to monitoring with or without 12-weekly CD4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2NRTI, mainly abacavir+lamivudine) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or 3 NRTIs as long-term ART...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29126299/cns-penetration-of-art-in-hiv-infected-children
#12
Malon Van den Hof, Charlotte Blokhuis, Sophie Cohen, Henriette J Scherpbier, Ferdinand W N M Wit, M C M Pistorius, Neeltje A Kootstra, Charlotte E Teunissen, Ron A A Mathot, Dasja Pajkrt
Background: Paediatric data on CNS penetration of antiretroviral drugs are scarce. Objectives: To evaluate CNS penetration of antiretroviral drugs in HIV-infected children and explore associations with neurocognitive function. Patients and methods: Antiretroviral drug levels were measured in paired CSF and blood samples of clinically stable HIV-infected children between 8 and 18 years old on long-term combined ART. Plasma drug concentrations were corrected for protein binding...
November 8, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29118985/acute-development-of-cushing-syndrome-in-an-hiv-infected-child-on-atazanavir-ritonavir-based-antiretroviral-therapy
#13
Gueorgui Dubrocq, Andrea Estrada, Shannon Kelly, Natella Rakhmanina
An 11-year-old male with perinatally acquired human immune deficiency virus (HIV) infection on antiretroviral regimen, which included abacavir plus lamivudine (Epzicom), didanosine, ritonavir and atazanavir presented with bilateral axillary striae, increased appetite, fatigue, facial swelling and acute weight gain. Two months prior to presentation, the patient had received a diagnostic and therapeutic intra-articular triamcinolone injection in the knee for pain relief and subsequently became progressively swollen in the face, developed striae bilaterally at the axillae, experienced increased appetite, fatigue and an 8 pound weight gain...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29105160/strength-in-amalgamation-newer-combination-agents-for-hiv-and-implications-for-practice
#14
Christopher McCoy, Melissa Badowski, Elizabeth Sherman, Rustin Crutchley, Ethan Smith, Daniel B Chastain
Antiretroviral (ART) therapy for treatment of human immunodeficiency virus (HIV) infection has undergone significant changes over the past 30 years. Many single tablet regimens (STR), including newer fixed dose combination (FDC) tablets, are available, offering patients several options for choosing a treatment regimen that works best for them. Given these changes, patients are more likely to adhere to treatment, achieve better clinical outcomes, and experience both fewer side effects and drug-drug interactions...
November 3, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29091219/dolutegravir-plus-abacavir-lamivudine-works-in-adolescents-but-size-matters
#15
Ferran Bossacoma Busquets, Antoni Noguera-Julian, Emilia Sanchez, Claudia Fortuny
No abstract text is available yet for this article.
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29078761/risk-of-cardiovascular-events-from-current-recent-and-cumulative-exposure-to-abacavir-among-persons-living-with-hiv-who-were-receiving-antiretroviral-therapy-in-the-united-states-a-cohort-study
#16
Kunchok Dorjee, Sanjiv M Baxi, Arthur L Reingold, Alan Hubbard
BACKGROUND: There is ongoing controversy regarding abacavir use in the treatment of HIV infection and the risk of subsequent development of cardiovascular disease. It is unclear how the risk varies as exposure accumulates. METHODS: Using an administrative health-plan dataset, risk of cardiovascular disease events (CVDe), defined as the first episode of an acute myocardial infarction or a coronary intervention procedure, associated with abacavir exposure was assessed among HIV-infected individuals receiving antiretroviral therapy across the U...
October 27, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29059031/dolutegravir-induced-liver-injury-leading-to-sub-acute-liver-failure-requiring-transplantation-a-case-report-and-review-of-literature
#17
Bo Wang, Laura Abbott, Kate Childs, Chris Taylor, Kosh Agarwal, Ian Cormack, Rosa Miquel, Abid Suddle
A patient with human immunodeficiency virus-1 infection presented with sub-acute liver failure, temporally related to commencement of an antiretroviral therapy regimen containing dolutegravir (Triumeq). The patient was not a carrier of HLA-B5701, and abacavir hypersensitivity was unlikely. We believe this is the first report of severe dolutegravir-related hepatotoxicity resulting in sub-acute liver failure and transplantation and highlights a potential need for closer monitoring after drug initiation.
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29058481/effects-of-antiretroviral-treatment-and-nadir-cd4-count-in-progression-to-cardiovascular-events-and-related-comorbidities-in-a-hiv-brazilian-cohort-a-multi-stage-approach
#18
Raquel de Vasconcellos Carvalhaes de Oliveira, Silvia Emiko Shimakura, Dayse Pereira Campos, Yara Hahr Marques Hökerberg, Flaviana Pavan Victoriano, Sayonara Ribeiro, Valdiléa G Veloso, Beatriz Grinsztejn, Marilia Sá Carvalho
The use of highly active antiretroviral therapy has resulted in changes of comorbidity profile in people living with HIV (PLHIV), increasing non-AIDS-related events. The occurrence of cardiovascular events is greater in PLHIV, but the mechanism responsible for it is still controversial. This article aimed to investigate factors associated with the progression to cardiovascular events in PLHIV using HAART. A 15-years cohort study with 1135 PLHIV was conducted in Rio de Janeiro-Brazil. Clinical progression was stratified in five states: No comorbidities (s1), arterial hypertension (s2), lipid abnormalities (s3), hypertension and lipid abnormalities (s4) and major cardiovascular events (stroke, coronary artery disease, thrombosis or death) (s5)...
October 23, 2017: AIDS Care
https://www.readbyqxmd.com/read/29054871/engineering-the-enantioselectivity-and-thermostability-of-a-%C3%AE-lactamase-from-microbacterium-hydrocarbonoxydans-for-the-kinetic-resolution-of-vince-lactam
#19
Shuaihua Gao, Shaozhou Zhu, Rong Huang, Hongxia Li, Hao Wang, Guojun Zheng
To produce promising biocatalysts, natural enzymes often need to be engineered to increase their catalytic performance. In this study, the enantioselectivity and thermostability of a (+)-γ-lactamase from Microbacterium hydrocarbonoxydans as the catalyst in the kinetic resolution of Vince lactam were improved. Enantiomerically pure (-)-Vince lactam is the key synthon in the synthesis of antiviral drugs such as carbovir and abacavir, which are used to fight against human HIV and hepatitis B viruses. The work was initialized by using the combinatorial active-site saturation test strategy to engineer the enantioselectivity of the enzyme...
October 20, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29040422/pharmacogenetics-a-general-review-on-progress-to-date
#20
Ann K Daly
Background: Pharmacogenetics is not a new subject area but its relevance to drug prescribing has become clearer in recent years due to developments in gene cloning and DNA genotyping and sequencing. Sources of data: There is a very extensive published literature concerned with a variety of different genes and drugs. Areas of agreement: There is general agreement that pharmacogenetic testing is essential for the safe use of drugs such as the thiopurines and abacavir...
October 11, 2017: British Medical Bulletin
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