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https://www.readbyqxmd.com/read/28627229/cobicistat-versus-ritonavir-similar-pharmacokinetic-enhancers-but-some-important-differences
#1
Alice Tseng, Christine A Hughes, Janet Wu, Jason Seet, Elizabeth J Phillips
OBJECTIVE: To describe properties of cobicistat and ritonavir; compare boosting data with atazanavir, darunavir, and elvitegravir; and summarize antiretroviral and comedication interaction studies, with a focus on similarities and differences between ritonavir and cobicistat. Considerations when switching from one booster to another are discussed. DATA SOURCES: A literature search of MEDLINE was performed (1985 to April 2017) using the following search terms: cobicistat, ritonavir, pharmacokinetic, drug interactions, booster, pharmacokinetic enhancer, HIV, antiretrovirals...
June 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28595364/antiretroviral-unbound-concentration-during-pregnancy-piece-of-interest-in-the-puzzle
#2
D Metsu, P L Toutain, E Chatelut, P Delobel, P Gandia
Atazanavir and darunavir total concentrations (drug bound to plasma proteins plus unbound drug) progressively decrease during pregnancy. This pharmacokinetic variation leads physicians to recommend increasing doses. Conversely, the unbound concentration (Cu), i.e. the pharmacologically active form of the drug, remains unchanged. The explanation of this desynchronization lies in the fact that the clearance of the unbound form, corresponding to the intrinsic metabolic capacity of the hepatocytes, is the only factor driving Cu, and is constant during pregnancy...
June 7, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28590329/antiretroviral-initiation-is-associated-with-increased-skeletal-muscle-area-and-fat-content
#3
Kristine M Erlandson, Suzanne Fiorillo, Fadzai Masawi, Ann Scherzinger, Grace A McComsey, Jordan E Lake, James H Stein, Judith S Currier, Todd T Brown
OBJECTIVE: A greater burden of physical function impairment occurs in HIV-infected adults; the impact of antiretroviral therapy (ART) initiation on muscle density (less dense = more fat), a measure of muscle quality, is unknown. DESIGN: AIDS Clinical Trials Group Study A5260 s, a cardiometabolic substudy of A5257, randomized HIV-infected, ART-naïve adults to ritonavir-boosted atazanavir, darunavir, or raltegravir with tenofovir/emtricitabine backbone. Single-slice abdominal computed tomography (CT) scans from baseline and week 96 were reanalyzed for lean muscle area and density...
June 5, 2017: AIDS
https://www.readbyqxmd.com/read/28582463/drug-resistance-testing-through-remote-genotyping-and-predicted-treatment-options-in-human-immunodeficiency-virus-type-1-infected-tanzanian-subjects-failing-first-or-second-line-antiretroviral-therapy
#4
Jenny Svärd, Sabina Mugusi, Doreen Mloka, Ujjwal Neogi, Genny Meini, Ferdinand Mugusi, Francesca Incardona, Maurizio Zazzi, Anders Sönnerborg
INTRODUCTION: Antiretroviral therapy (ART) has been successfully introduced in low-middle income countries. However an increasing rate of ART failure with resistant virus is reported. We therefore described the pattern of drug resistance mutations at antiretroviral treatment (ART) failure in a real-life Tanzanian setting using the remote genotyping procedure and thereafter predicted future treatment options using rule-based algorithm and the EuResist bioinformatics predictive engine. According to national guidelines, the default first-line regimen is tenofovir + lamivudine + efavirenz, but variations including nevirapine, stavudine or emtricitabine can be considered...
2017: PloS One
https://www.readbyqxmd.com/read/28579422/atazanavir-associated-crystalline-nephropathy
#5
Dominick Santoriello, Majdi Al-Nabulsi, Aravinda Reddy, Julius Salamera, Vivette D D'Agati, Glen S Markowitz
Crystalline nephropathy can occur following treatment with multiple therapeutic agents. We describe a human immunodeficiency virus (HIV)-infected patient treated for 2 years with combination antiretroviral therapy including atazanavir (ATV). Kidney biopsy revealed a crystalline nephropathy associated with diffuse chronic and granulomatous interstitial inflammation. Following the biopsy, treatment with ATV was discontinued and kidney function returned to pretreatment baseline levels. ATV, which has a well-established association with nephrolithiasis, is a rare but important cause of crystalline nephropathy...
June 2, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28553415/use-of-proviral-dna-to-investigate-virus-resistance-mutations-in-hiv-infected-zimbabweans
#6
Tutsirai V Musingwini, Danai T Zhou, Doreen Mhandire, Kerina Duri, Exnevia Gomo, Olav Oktedalen, Benjamin Chimukangara, Tinei Shamu, Sandra Shawarira-Bote, Collet Dandara, Babill Stray-Pedersen
BACKGROUND: Antiretroviral therapy (ART) to suppress HIV replication has reduced morbidity and mortality yet effectiveness of current HIV drugs is threatened by HIV drug resistance (HIVDR) mutations. OBJECTIVE: To determine HIVDR mutations using proviral DNA from specimens of patients presenting to an HIV treatment clinic. METHODS: DNA from 103 patients, 86 treatment-experienced, 17 treatment-naïve, were genotyped for the HIV-1C reverse transcriptase gene (RT; codons 21-304) using Sanger sequencing and sequences analyzed using Sequencher software...
2017: Open Microbiology Journal
https://www.readbyqxmd.com/read/28553123/the-hiv-protease-inhibitor-nelfinavir-as-a-novel-therapeutic-approach-for-the-treatment-of-refractory-pediatric-leukemia
#7
Vanessa Meier-Stephenson, Justin Riemer, Aru Narendran
PURPOSE: Refractory pediatric leukemia remains one of the leading causes of death in children. Intensification of current chemotherapy regimens to improve the outcome in these children is often limited by the effects of drug resistance and cumulative toxicity. Hence, the search for newer agents and novel therapeutic approaches are urgently needed to formulate the next-generation early-phase clinical trials for these patients. MATERIALS AND METHODS: A comprehensive library of antimicrobials, including eight HIV protease inhibitors (nelfinavir [NFV], saquinavir, indinavir, ritonavir, amprenavir, atazanavir, lopinavir, and darunavir), was tested against a panel of pediatric leukemia cells by in vitro growth inhibition studies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28522147/cardiovascular-risk-in-advanced-na%C3%A3-ve-hiv-infected-patients-starting-antiretroviral-therapy-comparison-of-three-different-regimens-prevaleat-ii-cohort
#8
Paolo Maggi, Chiara Bellacosa, Armando Leone, Anna Volpe, Elena Delfina Ricci, Nicoletta Ladisa, Stefania Cicalini, Elisabetta Grilli, Rosaria Viglietti, Antonio Chirianni, Lara Ines Bellazzi, Renato Maserati, Canio Martinelli, Paola Corsi, Benedetto Maurizio Celesia, Federica Sozio, Gioacchino Angarano
BACKGROUND AND AIMS: PREVALEAT (PREmature VAscular LEsions and Antiretroviral Therapy) II is a multicenter, longitudinal cohort study aimed at the evaluation of cardiovascular risk among advanced HIV-positive, treatment-naïve patients starting their first therapy. We hypothesized that these patients, present a higher cardiovascular (CV) risk. METHODS: The study included all consecutive naïve patients with less than 200 CD4 cells/ml starting antiretroviral therapy...
May 5, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28520618/defining-a-cut-off-for-atazanavir-in-hair-samples-associated-with-virological-failure-among-adolescents-failing-second-line-antiretroviral-treatment
#9
Tariro Dianah Chawana, Monica Gandhi, Kusum Nathoo, Bernard Ngara, Alexander Louie, Howard Horng, David Katzenstein, John Metcalfe, Charles Fungai Brian Nhachi
BACKGROUND: Adequate antiretroviral exposure is crucial for virological suppression. We assessed the relationship between atazanavir hair levels with self-reported adherence, virological outcomes, and the effect of a home-based adherence intervention in HIV-infected adolescents failing 2-line antiretroviral treatment in Zimbabwe. METHODS: HIV-infected adolescents on atazanavir/ritonavir-based 2-line treatment for ≥6 months with viral load (VL) >1,000 copies/ml were randomised to either standard care (control) or standard care plus modified directly administered antiretroviral therapy (mDAART) (intervention)...
May 17, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28492392/predictors-of-estimated-glomerular-filtration-rate-progression-stabilization-or-improvement-after-chronic-renal-impairment-in-hiv-positive-individuals
#10
Lene Ryom, Amanda Mocroft, Ole Kirk, Peter Reiss, Michael Ross, Colette Smith, Olivier Moranne, Philippe Morlat, Christoph A Fux, Caroline Sabin, Andrew Phillips, Matthew Law, Jens D Lundgren
OBJECTIVES: The objectives of this analysis were to investigate predictors of progression, stabilization or improvement in estimated glomerular filtration rate (eGFR) after development of chronic renal impairment (CRI) in HIV-positive individuals. DESIGN: Prospective observational study. METHODS: The Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study participants progressing to CRI defined as confirmed, at least 3 months apart, and eGFR 70 ml/min per 1...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28482097/once-daily-atazanavir-cobicistat-and-darunavir-cobicistat-exposure-over-72%C3%A2-h-post-dose-in-plasma-urine-and-saliva-contribution-to-drug-pharmacokinetic-knowledge
#11
Emilie R Elliot, Alieu Amara, Nicole Pagani, Laura Else, Graeme Moyle, Alex Schoolmeesters, Chris Higgs, Saye Khoo, Marta Boffito
No abstract text is available yet for this article.
May 6, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28458569/erratum-budget-impact-analysis-of-the-simplification-to-atazanavir-ritonavir-lamivudine-dual-therapy-of-hiv-positive-patients-receiving-atazanavir-based-triple-therapies-in-italy-starting-from-data-of-the-atlas-m-trial-corrigendum
#12
https://www.readbyqxmd.com/read/28443391/atazanavir-sulfate-cobicistat-for-the-treatment-of-hiv-infection
#13
Francisco Antunes
During last two decades several drugs were developed to offer long-term benefits in terms of virologic efficacy, favourable tolerability and toxicity profiles in treatment of HIV infection. Pharmacokinetics boosting of protease inhibitor allows a higher genetic barrier, as few or no drug-resistant mutations are detected in patients with virologic failure. Areas covered: Atazanavir sulfate + cobicistat (ATV/c) was recently approved for the treatment of HIV-1 infection. Bioequivalence between cobicistat (COBI) and ritonavir (RTV) as a pharmacoenhancer of ATV was established...
June 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28438550/lipophilic-salts-of-poorly-soluble-compounds-to-enable-high-dose-lipidic-sedds-formulations-in-drug-discovery
#14
Michael Morgen, Ajay Saxena, Xue-Qing Chen, Warren Miller, Richard Nkansah, Aaron Goodwin, Jon Cape, Roy Haskell, Ching Su, Olafur Gudmundsson, Michael Hageman, Anoop Kumar, Gajendra Singh Chowan, Abhijith Rao, Vinay K Holenarsipur
Self-emulsifying drug delivery systems (SEDDS) have been used to solubilize poorly water-soluble drugs to improve exposure in high-dose pharmacokinetic (PK) and toxicokinetic (TK) studies. However, the absorbable dose is often limited by drug solubility in the lipidic SEDDS vehicle. This study focuses on increasing solubility and drug loading of ionizable drugs in SEDDS vehicles using lipophilic counterions to prepare lipophilic salts of drugs. SEDDS formulations of two lipophilic salts-atazanavir-2-naphthalene sulfonic acid (ATV-2-NSA) and atazanavir-dioctyl sulfosuccinic acid (ATV-Doc)-were characterized and their performance compared to atazanavir (ATV) free base formulated as an aqueous crystalline suspension, an organic solution, and a SEDDS suspension, using in vitro, in vivo, and in silico methods...
April 21, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28424561/response-by-gender-of-hiv-1-infected-subjects-treated-with-abacavir-lamivudine-plus-atazanavir-with-or-without-ritonavir-for-144-weeks
#15
Kathleen E Squires, Benjamin Young, Lizette Santiago, Robin H Dretler, Sharon L Walmsley, Henry H Zhao, Gary E Pakes, Lisa L Ross, Mark S Shaefer
PURPOSE: The 144-week results of the open-label, multicenter Atazanavir/Ritonavir Induction with Epzicom Study (ARIES) were stratified by gender to compare treatment responses. METHODS: A total of 369 HIV-infected, antiretroviral-naïve subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r) whose HIV-1 RNA was <50 copies/mL by week 30 were randomized 1:1 at week 36 to maintain or discontinue ritonavir for 108 subsequent weeks. Between- and within-treatment gender-related efficacy and safety differences were analyzed...
2017: HIV/AIDS: Research and Palliative Care
https://www.readbyqxmd.com/read/28407075/once-daily-atazanavir-cobicistat-and-darunavir-cobicistat-exposure-over-72%C3%A2-h-post-dose-in-plasma-urine-and-saliva-contribution-to-drug-pharmacokinetic-knowledge
#16
Emilie R Elliot, Alieu Amara, Nicole Pagani, Laura Else, Graeme Moyle, Alex Schoolmeesters, Chris Higgs, Saye Khoo, Marta Boffito
Background: We investigated the pharmacokinetics (PK) of atazanavir/cobicistat and darunavir/cobicistat once daily over 72 h following drug intake cessation in plasma, saliva and urine. Methods: Healthy volunteers received a fixed-dose combination of 300/150 mg of atazanavir/cobicistat once daily for 10 days, followed by a 10 day washout period and then a fixed-dose combination of 800/150 mg of darunavir/cobicistat once daily for 10 days. Full PK profiles were assessed for each phase for 72 h following day 10 and parameters determined to the last measurable concentration in plasma, saliva and urine by non-compartmental methods...
April 12, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28403692/severe-hypokalemia-due-to-a-possible-drug-drug-interaction-between-vinblastine-and-antiretrovirals-in-a-hiv-infected-patient-with-hodgkin-s-lymphoma
#17
Ezequiel Cordova, Laura Morganti, Andrea Odzak, Florencia Arcondo, Mariana Silva, Marcelo Zylberman, Claudia Rodriguez
A 60-year-old HIV-1 infected woman on antiretroviral therapy (emtricitabine/tenofovir, and ritonavir-boosted atazanavir) developed Hodgkin's lymphoma. The patient initiated ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy and presented with neutropenia and severe hypokalemia. Hypokalemia was considered as part of a proximal tubular renal dysfunction, and other causes of hypokalemia were excluded. Due to suspicion of drug--drug interactions between antiretrovirals and vinblastine, ritonavir-boosted atazanavir was switched to dolutegravir and the patient continued emtricitabine/tenofovir...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28403052/second-and-third-line-antiretroviral-therapy-for-children-and-adolescents-a-scoping-review
#18
REVIEW
Erica Lazarus, Simone Nicol, Lisa Frigati, Martina Penazzato, Mark F Cotton, Elizabeth Centeno-Tablante, Avy Violari, Liesl Nicol
BACKGROUND: The World Health Organization identified a need for evidence to inform revision of second- and third-line antiretroviral therapy (ART) options in children failing ART. We performed an in-depth scoping review of all available literature on second-line and subsequent ART regimens in children younger than 18 years. METHODS: We comprehensively searched, without language or date limitations, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials...
May 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28399819/comparison-of-atazanavir-ritonavir-and-darunavir-ritonavir-based-antiretroviral-therapy-for-antiretroviral-na%C3%A3-ve-patients
#19
Tony Antoniou, Leah Szadkowski, Sharon Walmsley, Curtis Cooper, Ann N Burchell, Ahmed M Bayoumi, Julio S G Montaner, Mona Loutfy, Marina B Klein, Nima Machouf, Christos Tsoukas, Alexander Wong, Robert S Hogg, Janet Raboud
BACKGROUND: Atazanavir/ritonavir and darunavir/ritonavir are common protease inhibitor-based regimens for treating patients with HIV. Studies comparing these drugs in clinical practice are lacking. METHODS: We conducted a retrospective cohort study of antiretroviral naïve participants in the Canadian Observational Cohort (CANOC) collaboration initiating atazanavir/ritonavir- or darunavir/ritonavir-based treatment. We used separate Fine and Gray competing risk regression models to compare times to regimen failure (composite of virologic failure or discontinuation for any reason)...
April 11, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28398959/emergence-of-untreatable-multidrug-resistant-hiv-1-in-patients-failing-second-line-therapy-in-kenya
#20
Seth C Inzaule, Raph L Hamers, Irene Mukui, Kennedy Were, Prestone Owiti, Daniel Kwaro, Tobias F Rinke de Wit, Clement Zeh
: We performed a countrywide assessment of HIV drug resistance among 123 patients with virological failure on second-line antiretroviral therapy (ART) in Kenya. The percentage of patients harbouring intermediate-to-high-level resistance was 27% for lopinavir-ritonavir, 24% for atazanavir-ritonavir and 7% for darunavir-ritonavir, and 25% had complete loss of activity to all available first and second-line drugs. Overall, one in four patients failing second-line ART have completely exhausted available antiretrovirals in Kenya, highlighting the need for increased access to third-line drugs...
June 19, 2017: AIDS
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