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https://www.readbyqxmd.com/read/29165225/prevalence-of-asymptomatic-parasitemia-and-gametocytemia-in-hiv-infected-children-on-differing-antiretroviral-therapy
#1
Charlotte V Hobbs, Erin E Gabriel, Portia Kamthunzi, Gerald Tegha, Jean Tauzie, Yonghua Li, Tiina Ilmet, Elena Artimovich, Jillian Neal, Ted Hall, Sunil Parikh, Brian Kirmse, Patrick Jean-Philippe, Jingyang Chen, William R Prescott, Paul Palumbo, Patrick E Duffy, William Borkowsky, For The P S Study Team
Laboratory data and prior pediatric reports indicate that HIV protease inhibitor (PI)-based antiretroviral therapy (ARV) kills gametocytes and reduces rates of gametocytemia, but not asymptomatic parasitemia, in a high malaria-transmission area. To determine whether ARV regimen impacts these rates in areas with less-intense malaria transmission, we compared asymptomatic parasitemia and gametocytemia rates in HIV-infected children by ARV regimen in Lilongwe, Malawi, an area of low-to-moderate transmission intensity...
November 20, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29161753/improving-the-efficacy-of-proteasome-inhibitors-in-the-treatment-of-renal-cell-carcinoma-by-combination-with-the-hiv-protease-inhibitors-lopinavir-or-nelfinavir
#2
Dominik Abt, Andrej Besse, Lenka Sedlarikova, Marianne Kraus, Juergen Bader, Tobias Silzle, Martina Vodinska, Ondrej Slaby, Hans-Peter Schmid, Daniel Stephan Engeler, Christoph Driessen, Lenka Besse
OBJECTIVES: To assess the potential of second-generation proteasome inhibition by carfilzomib and its combination with the HIV-protease inhibitors (HIV-PIs) lopinavir and nelfinavir in vitro for improved treatment of clear cell renal cell cancer (ccRCC). MATERIALS AND METHODS: Cytotoxicity, reactive oxygen species (ROS) production and unfolded protein response (UPR) activation of proteasome inhibitors, HIV-PIs and their combination was assessed in 3 cell lines and primary cells derived from 3 ccRCC tumors by MTS assay, flow cytometry, quantitative PCR and western blot, respectively...
November 21, 2017: BJU International
https://www.readbyqxmd.com/read/29159965/improvement-in-lipids-after-switch-to-boosted-atazanavir-or-darunavir-in-children-adolescents-with-perinatally-acquired-hiv-on-older-protease-inhibitors-results-from-the-pediatric-hiv-aids-cohort-study
#3
J Jao, W Yu, K Patel, T L Miller, B Karalius, M E Geffner, L A DiMeglio, A Mirza, J S Chen, M Silio, E J McFarland, R B Van Dyke, D Jacobson
OBJECTIVES: Dyslipidaemia is common in perinatally HIV-infected (PHIV) youth receiving protease inhibitors (PIs). Few studies have evaluated longitudinal lipid changes in PHIV youth after switch to newer PIs. METHODS: We compared longitudinal changes in fasting lipids [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and TC:HDL-C ratio] in PHIV youth enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) study who switched to atazanavir/ritonavir (ATV/r)- or darunavir/ritonavir (DRV/r)-based antiretroviral therapy (ART) from an older PI-based ART and those remaining on an older PI...
November 21, 2017: HIV Medicine
https://www.readbyqxmd.com/read/29143565/hiv-1-resistance-rarely-observed-in-subjects-using-darunavir-once-daily-regimens-across-clinical-studies
#4
Erkki Lathouwers, Eric Y Wong, Donghan Luo, Sareh Seyedkazemi, Sandra De Meyer, Kimberley Brown
BACKGROUND: Darunavir 800 mg once daily (QD) is indicated for HIV-1-infected treatment-naïve and treatment-experienced (without darunavir resistance-associated mutations [RAMs]) individuals, and has been evaluated in phase 2/3 studies with durations between 48 and 192 weeks. OBJECTIVE: To summarize the development (or identification) of post-baseline resistance (RAMs and antiretroviral phenotypic susceptibility) among subjects receiving darunavir QD dosing. METHODS: Seven phase 2/3 studies with available genotypes/phenotypes for subjects treated with ritonavir- or cobicistat-boosted darunavir 800 mg QD regimens were assessed: ARTEMIS (NCT00258557; n = 343), GS-US-299-0102 (NCT01565850; n = 153), GS-US-216-0130 (NCT01440569; n = 313), ODIN (NCT00524368; n = 294), INROADS (NCT01199939; n = 54), MONET (NCT00458302; n = 256), and PROTEA (NCT01448707; n = 273)...
November 16, 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/29140932/characteristics-of-treatment-experienced-hiv-infected-african-children-and-adolescents-initiating-darunavir-and-or-etravirine-based-antiretroviral-treatment
#5
Bethany Corrigan, Irene Mukui, Lloyd Mulenga, Nobuhle Mthethwa, Mosilinyane Letsie, Stephanie Bruno, Natella Rakhmanina
BACKGROUND: Data are limited on the selection and sequencing of second and third-line pediatric antiretroviral treatment (ART) in resource-limited settings. This study aimed to evaluate characteristics of African pediatric patients initiated on darunavir (DRV) and/or etravirine (ETR) through a specific drug donation program. METHODS: This was a cross-sectional study of baseline immunologic, virologic and demographic characteristics of children and adolescents initiating DRV- and/or ETR-based ART...
November 14, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29136115/estradiol-levels-are-altered-in-human-immunodeficiency-virus-infected-pregnant-women-randomized-to-efavirenz-versus-lopinavir-ritonavir-based-antiretroviral-therapy
#6
Chloe R McDonald, Andrea L Conroy, Joel L Gamble, Eszter Papp, Michael Hawkes, Peter Olwoch, Paul Natureeba, Moses Kamya, Michael Silverman, Deborah Cohan, Catherine A Koss, Grant Dorsey, Kevin C Kain, Lena Serghides
Background: Combination antiretroviral therapy (cART) use in pregnancy has been associated with hormonal dysregulation. We performed a secondary retrospective analysis of longitudinal progesterone and estradiol levels in pregnancy using specimens from the Protease Inhibitors to Reduce Malaria Morbidity in HIV-infected Pregnant Women study, which randomized Ugandan human immunodeficiency virus (HIV)-infected ART-naive women to initiate either lopinavir/ritonavir (LPV/r)-based or efavirenz (EFV)-based cART...
November 10, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29135577/protease-inhibitors-and-preterm-delivery-another-piece-in-the-puzzle
#7
Graziella Favarato, Claire L Townsend, Heather Bailey, Helen Peters, Pat Tookey, Graham P Taylor, Claire Thorne
BACKGROUND: Questions remain regarding preterm delivery (PTD) risk in HIV-infected women on antiretroviral therapy (ART), including the role of ritonavir-boosted protease inhibitors (PI/r), timing of ART initiation and immune status. METHODS: We examined data from the UK/Ireland National Study of HIV in Pregnancy and Childhood on women with HIV delivering a singleton live infant in 2007-2015, including those pregnancies receiving PI/r-based (n=4184) or non-nucleoside reverse transcriptase inhibitors (NNRTI)-based regimens (n = 1889)...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29133558/pharmacokinetics-and-drug-drug-interactions-of-lopinavir-ritonavir-administered-with-first-and-second-line-antituberculosis-drugs-in-hiv-infected-children-treated-for-multidrug-resistant-tuberculosis
#8
Louvina E van der Laan, Anthony J Garcia-Prats, H Simon Schaaf, Tjokosela Tikiso, Lubbe Wiesner, Mine de Kock, Jana Winckler, Jennifer Norman, Helen McIlleron, Paolo Denti, Anneke C Hesseling
Background Lopinavir/ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs in young children in high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir/ritonavir. We describe the pharmacokinetics of and potential drug-drug interactions between lopinavir/ritonavir and routine drugs used for MDR-TB treatment in HIV-infected children.Methods A combined population pharmacokinetic model was developed to jointly describe the pharmacokinetics of lopinavir and ritonavir in 32 HIV-infected children (16 on MDR-TB treatment with combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, a fluoroquinolone, and amikacin: and 16 without TB), who were established on a lopinavir/ritonavir-containing antiretroviral regimen...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29126299/cns-penetration-of-art-in-hiv-infected-children
#9
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/29112069/neuropsychological-performance-in-african-children-with-hiv-enrolled-in-a-multi-site-anti-retroviral-clinical-trial
#10
Michael J Boivin, Linda Barlow-Mosha, Miriam Chernoff, Barbara Laughton, Bonnie Zimmer, Celeste Joyce, Mutsa Bwakura-Dangarembizi, Mmule Ratswana, Nasreen Abrahams, Lee Fairlie, Hermien Gous, Portia Kamthunzi, Katie McCarthy, Itziar Familiar-Lopez, Patrick Jean-Phillippe, Joan Coetzee, Avy Violari, Mark Cotton, Paul Palumbo
OBJECTIVE & DESIGN: Children with HIV infection (HIV+) are at neuropsychological risk, but few studies have evaluated this at multiple sites in low and middle income countries (LMICs). We compared neuropsychological outcomes at enrollment (>5 yrs age) among HIV+, HIV-uninfected perinatally-exposed (HEU), and HIV unexposed (HU) children from 4 sub-Saharan countries. METHODS: IMPAACT P1060 compared Nevirapine (NVP) versus Lopinavir/Ritonavir (LPVr)-based ART in HIV-infected children 6 to 35 months of age...
November 2, 2017: AIDS
https://www.readbyqxmd.com/read/29108797/lopinavir-plus-nucleoside-reverse-transcriptase-inhibitors-lopinavir-plus-raltegravir-or-lopinavir-monotherapy-for-second-line-treatment-of-hiv-earnest-144-week-follow-up-results-from-a-randomised-controlled-trial
#11
James G Hakim, Jennifer Thompson, Cissy Kityo, Anne Hoppe, Andrew Kambugu, Joep J van Oosterhout, Abbas Lugemwa, Abraham Siika, Raymond Mwebaze, Aggrey Mweemba, George Abongomera, Margaret J Thomason, Philippa Easterbrook, Peter Mugyenyi, A Sarah Walker, Nicholas I Paton
BACKGROUND: Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings...
November 3, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29099779/self-emulsifying-granules-and-pellets-composition-and-formation-mechanisms-for-instant-or-controlled-release
#12
REVIEW
Ioannis Nikolakakis, Ioannis Partheniadis
Many articles have been published in the last two decades demonstrating improvement in the dissolution and absorption of low solubility drugs when formulated into self-emulsifying drug delivery systems (SEDDS). Several such pharmaceutical products have appeared in the market for medium dose (Neoral(®) for Cyclsoprin A, Kaletra(®) for Lopinavir and Ritonavir), or low dose medications (Rocaltrol(®) for Calcitriol and Avodart(®) for Dutasteride). However, these are in the form of viscous liquids or semisolid presentations, characterized by the disadvantages of high production cost, stability problems and the requirement of large quantities of surfactants...
November 3, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29098809/gp41-and-gag-amino-acids-linked-to-hiv-1-protease-inhibitor-based-second-line-failure-in-hiv-1-subtype-a-from-western-kenya
#13
Mia Coetzer, Lauren Ledingham, Lameck Diero, Emmanuel Kemboi, Millicent Orido, Rami Kantor
INTRODUCTION: Failure of protease-inhibitor (PI)-based second-line antiretroviral therapy (ART) with medication adherence but no protease drug resistance mutations (DRMs) is not well understood. This study investigated the involvement of gp41 and gag as alternative mechanisms, not captured by conventional resistance testing and particularly relevant in resource-limited settings where third-line ART is limited. METHODS: We evaluated gp41 and gag for unique amino acids in seven subtype A infected Kenyans failing second-line therapy with no PI resistance yet detectable lopinavir (query dataset), compared to seven similar-setting patients with PI resistance or undetectable lopinavir and 69 publically available subtype A Kenyan whole-genomes sequences...
November 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/29091279/hbv-hcv-and-hbv-hcv-co-infection-among-hiv-positive-patients-in-hunan-province-china-regimen-selection-hepatotoxicity-and-antiretroviral-therapy-outcome
#14
Shu Su, Christopher Kincaid Fairley, Joe Sasadeusz, Jianmei He, Xiuqing Wei, Huan Zeng, Jun Jing, Limin Mao, Xi Chen, Lei Zhang
Background Co-infection with hepatitis B (HBV) and C (HCV) is common among people living with HIV (PLHIV). This study investigates the impacts of hepatitis co-infection on antiretroviral therapy (ART) outcomes and hepatotoxicity in PLHIV. Methods The cohort study included 1,984 PLHIV. Hepatotoxicity was defined by elevated alanine aminotransferase (ALT) levels. ART outcomes were measured by CD4 cell counts, viral load and mortality rate in patients. Results Among 1,984 PLHIV, 184 (9.3%) were co-infected with HBV and 198 (10...
November 1, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29091217/tenofovir-disoproxil-fumarate-emtricitabine-plus-ritonavir-boosted-lopinavir-or-cobicistat-boosted-elvitegravir-as-a-single-tablet-regimen-for-hiv-post-exposure-prophylaxis
#15
A Inciarte, L Leal, E González, A León, C Lucero, J Mallolas, B Torres, M Laguno, J Rojas, M Martínez-Rebollar, A González-Cordón, A Cruceta, J A Arnaiz, J M Gatell, F García
Objectives: To assess HIV-1 post-exposure prophylaxis (PEP) non-completion at day 28, comparing ritonavir-boosted lopinavir versus cobicistat-boosted elvitegravir as a single-tablet regimen (STR), using tenofovir disoproxil fumarate/emtricitabine with both of these therapies. Methods: A prospective, open, randomized clinical trial was performed. Individuals attending the emergency room due to potential sexual exposure to HIV and who met criteria for PEP were randomized 1:3 into two groups receiving either 400/100 mg of lopinavir/ritonavir (n = 38) or 150/150 mg of elvitegravir/cobicistat (n = 119), with both groups also receiving 245/200 mg of tenofovir disoproxil fumarate/emtricitabine...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29082041/ritonavir-boosted-darunavir-plus-two-nucleoside-reverse-transcriptase-inhibitors-versus-other-regimens-for-initial-antiretroviral-therapy-for-people-with-hiv-infection-a-systematic-review
#16
REVIEW
Tatevik Balayan, Hacsi Horvath, George W Rutherford
BACKGROUND: Darunavir is a second-generation protease-inhibitor used with ritonavir (DRV/r) and two nucleoside reverse-transcriptase inhibitors as an option in first-line antiretroviral treatment (ART). METHODS: We systematically reviewed randomized controlled trials (RCTs) of DRV/r versus other regimens in patients initiating ART. We searched five bibliographic databases and other key resources. We had no language limitations. We assessed bias risk with the Cochrane tool and used GRADE to assess evidence quality...
2017: AIDS Research and Treatment
https://www.readbyqxmd.com/read/29064386/the-role-of-pxr-genotype-and-transporter-expression-in-the-placental-transport-of-lopinavir-in-mice
#17
Sarabjit S Gahir, Micheline Piquette-Miller
Lopinavir (LPV), an antiretroviral protease inhibitor frequently prescribed in HIV-positive pregnancies, is a substrate of Abcb1 and Abcc2. As differences in placental expression of these transporters were seen in Pregnane X Receptor (PXR) -/- mice, we examined the impact of placental transporter expression and fetal PXR genotype on the fetal accumulation of LPV. PXR +/- dams bearing PXR +/+, PXR +/-, and PXR -/- fetuses were generated by mating PXR +/- female mice with PXR +/- males. On gestational day 17, dams were administered 10 mg/kg LPV (i...
October 24, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29061086/pharmacogenetics-based-population-pharmacokinetic-analysis-of-tenofovir-in-thai-hiv-infected-patients
#18
Kanokrat Rungtivasuwan, Anchalee Avihingsanon, Narukjaporn Thammajaruk, Siwaporn Mitruk, David M Burger, Kiat Ruxrungtham, Chonlaphat Sukasem, Baralee Punyawudho
AIM: To develop a population pharmacokinetic model and identify sources of variability, genetic and nongenetic factors, of tenofovir. METHODS: The ABCC2 and ABCC4 polymorphisms were genotyped in 342 patients. A nonlinear mixed effects model was used to develop the population pharmacokinetic model and investigate the influence of these polymorphisms and other patient specific covariates on the pharmacokinetics of tenofovir. RESULTS: The estimated glomerular filtration rate calculated by the Cockcroft and Gault equation, concomitant use of lopinavir/ritonavir and ABCC4 3463A>G polymorphism were associated with tenofovir apparent oral clearance (CL/F)...
October 24, 2017: Pharmacogenomics
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
#19
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/29052340/absence-of-neurocognitive-disadvantage-associated-with-paediatric-hiv-subtype-a-infection-in-children-on-antiretroviral-therapy
#20
Paul Bangirana, Theodore D Ruel, Michael J Boivin, Satish K Pillai, Leila B Giron, Alla Sikorskii, Asish Banik, Jane Achan
INTRODUCTION: Infection with HIV subtype A has been associated with poorer neurocognitive outcomes compared to HIV subtype D in Ugandan children not eligible for antiretroviral therapy (ART). In this study, we sought to determine whether subtype-specific differences are also observed among children receiving ART. MATERIALS AND METHODS: Children were recruited from a clinical trial in which they were randomized to receive either lopinavir (LPV)- or non-nucleoside reverse transcriptase inhibitor (NNRTI)- based ART (NCT00978068)...
October 2017: Journal of the International AIDS Society
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