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https://www.readbyqxmd.com/read/27901085/wide-variation-in-susceptibility-of-transmitted-founder-hiv-1-subtype-c-isolates-to-protease-inhibitors-and-association-with-in-vitro-replication-efficiency
#1
Katherine A Sutherland, Dami A Collier, Daniel T Claiborne, Jessica L Prince, Martin J Deymier, Richard A Goldstein, Eric Hunter, Ravindra K Gupta
The gag gene is highly polymorphic across HIV-1 subtypes and contributes to susceptibility to protease inhibitors (PI), a critical class of antiretrovirals that will be used in up to 2 million individuals as second-line therapy in sub Saharan Africa by 2020. Given subtype C represents around half of all HIV-1 infections globally, we examined PI susceptibility in subtype C viruses from treatment-naïve individuals. PI susceptibility was measured in a single round infection assay of full-length, replication competent MJ4/gag chimeric viruses, encoding the gag gene and 142 nucleotides of pro derived from viruses in 20 patients in the Zambia-Emory HIV Research Project acute infection cohort...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895016/are-prophylactic-and-therapeutic-target-concentrations-different-the-case-of-lopinavir-ritonavir-or-lamivudine-administered-to-infants-for-the-prevention-of-mother-to-child-hiv-1-transmission-during-breastfeeding
#2
Frantz Foissac, Jörn Blume, Jean-Marc Tréluyer, Thorkild Tylleskär, Chipepo Kankasa, Nicolas Meda, James K Tumwine, Mandisa Singata-Madliki, Kim Harper, Silvia M Illamola, Naïm Bouazza, Nicolas Nagot, Philippe Van de Perre, Stéphane Blanche, Déborah Hirt
The ANRS 12174 trial assessed the efficacy and tolerance of LPV/r versus 3TC prophylaxis administered to breastfed infants, whose HIV-infected mothers were not on ART. In this sub-study, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at week 6, 26 and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters based on previously published pharmacokinetic models for HIV-infected children...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27890952/a-study-of-antiretroviral-resistance-patterns-in-treatment-experienced-and-naive-human-immunodeficiency-virus-infected-patients
#3
Raj Harjani, Ram Malkani
BACKGROUND: About 10% of the patients had surveillance drug-related mutations for nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in an Indian study. It was also reported that resistance was maximum for nucleoside reverse transcriptase inhibitors (NRTIs) and minimum for PIs. METHODS: The present study was a cross-sectional assessment of 21 human immunodeficiency virus (HIV)-infected individuals attending a HIV care center in a tertiary care center in Mumbai, Maharashtra, India...
July 2016: Indian Journal of Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/27889708/mir-34a-is-a-common-link-in-both-hiv-and-antiretroviral-therapy-induced-vascular-aging
#4
Jiaxin Zhan, Shanshan Qin, Lili Lu, Xiamin Hu, Jun Zhou, Yeying Sun, Jian Yang, Ying Liu, Zunzhe Wang, Ning Tan, Jiyan Chen, Chunxiang Zhang
Both HIV and antiretroviral therapy could induce vascular aging with unclear mechanisms. In this study, via microarray analysis, we identified, for the first time, that miR-34a expression was significantly increased in both HIV-infected, and antiretroviral agents-treated vessels and vascular endothelial cells (ECs) from these vessels. In cultured ECs, miR-34a expression was significantly increased by HIV-Tat protein and by the antiretroviral agents, lopinavir/ritonavir. Both HIV-Tat protein and antiretroviral agents could induce EC senescence, which was inhibited by miR-34a inhibition...
November 26, 2016: Aging
https://www.readbyqxmd.com/read/27888600/-darunavir-cobicistat-monotherapy-experience-in-a-tertiary-hospital
#5
L Yunquera-Romero, R Asensi-Díez, J C Del Rio-Valencia, I Muñoz-Castillo, M A Castaño-Carracedo
OBJECTIVE: Ritonavir-boosted protease inhibitor (IP/r) monotherapy: darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pretreated patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), reduce costs and simplify antiretroviral treatment. To start IP/r monotherapy, according to GESIDA guidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, plasma viral load <50 copies/ mL for at least 6 months and absence of protease inhibitors mutations or previous virologic failures to IP/r...
December 2016: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/27875362/relationship-between-hiv-infection-antiretroviral-therapy-inflammatory-markers-and-cerebrovascular-endothelial-function-among-adults-in-urban-china
#6
Felicia C Chow, Yanling Li, Yinghuan Hu, Joy Chan, Huanling Wang, Weihai Xu, Richard W Price, Farzaneh A Sorond, Taisheng Li
BACKGROUND: Cerebrovascular risk is increased in people living with HIV infection compared with age-matched uninfected individuals. Cerebrovascular endothelial dysfunction related to antiretroviral therapy and inflammation may contribute to higher stroke risk in HIV infection. METHODS: We compared cerebral vasoreactivity-a measure of cerebrovascular endothelial function assessed by the breath holding index (BHI) using transcranial Doppler ultrasound-between virologically suppressed Chinese HIV-infected individuals followed in an HIV clinic in Beijing, China and uninfected controls...
November 21, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/27828808/managing-chronic-kidney-disease-in-the-older-adults-living-with-hiv
#7
Frank A Post
PURPOSE OF REVIEW: HIV replication and immunodeficiency are important risk factors for chronic kidney disease (CKD). Widespread use of antiretrovirals that may affect kidney function underscores the need for monitoring kidney function, allowing early detection of drug-induced kidney injury and identification of patients who may benefit from antiretroviral therapy switches. RECENT FINDINGS: Several cohorts have reported an increased incidence of CKD with tenofovir [tenofovir disoproxil fumarate (TDF)], atazanavir, and lopinavir, and CKD risk scores have been developed to identify those most at risk of kidney disease progression while receiving these agents...
November 8, 2016: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/27821443/altered-plasmodium-falciparum-sensitivity-to-the-antiretroviral-protease-inhibitor-lopinavir-associated-with-polymorphisms-in-pfmdr1
#8
Ebere Sonoiki, Christian Nsanzabana, Jennifer Legac, Kirthana Mysore Vasudevarao Sindhe, Joseph DeRisi, Philip J Rosenthal
The HIV protease inhibitor lopinavir inhibits Plasmodium falciparum aspartic proteases (plasmepsins) and parasite development, and children receiving lopinavir-ritonavir experienced fewer episodes of malaria than those receiving other antiretroviral regimens. Resistance to lopinavir was selected in vitro over ∼9 months, with ∼4-fold decreased sensitivity. Whole genome sequencing of resistant parasites showed a mutation and increased copy number in pfmdr1, a mutation in a protein of unknown function, but no polymorphisms in plasmepsin genes...
November 7, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27815068/body-composition-and-metabolic-outcomes-after-96-weeks-of-treatment-with-ritonavir-boosted-lopinavir-plus-either-nucleoside-or-nucleotide-reverse-transcriptase-inhibitors-or-raltegravir-in-patients-with-hiv-with-virological-failure-of-a-standard-first-line
#9
Mark A Boyd, Janaki Amin, Patrick W G Mallon, Nagalingeswaran Kumarasamy, Johan Lombaard, Robin Wood, Ploenchan Chetchotisakd, Praphan Phanuphak, Lerato Mohapi, Iskandar Azwa, Waldo H Belloso, Jean-Michel Molina, Jennifer Hoy, Cecilia L Moore, Sean Emery, David A Cooper
BACKGROUND: Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir...
November 1, 2016: Lancet HIV
https://www.readbyqxmd.com/read/27806243/benefits-and-risks-of-antiretroviral-therapy-for-perinatal-hiv-prevention
#10
Mary G Fowler, Min Qin, Susan A Fiscus, Judith S Currier, Patricia M Flynn, Tsungai Chipato, James McIntyre, Devasena Gnanashanmugam, George K Siberry, Anne S Coletti, Taha E Taha, Karin L Klingman, Francis E Martinson, Maxensia Owor, Avy Violari, Dhayendre Moodley, Gerhard B Theron, Ramesh Bhosale, Raziya Bobat, Benjamin H Chi, Renate Strehlau, Pendo Mlay, Amy J Loftis, Renee Browning, Terence Fenton, Lynette Purdue, Michael Basar, David E Shapiro, Lynne M Mofenson
Background Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. Methods We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART)...
November 3, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27803888/genetic-and-epigenetic-interspecies-networks-for-cross-talk-mechanisms-in-human-macrophages-and-dendritic-cells-during-mtb-infection
#11
Cheng-Wei Li, Yun-Lin Lee, Bor-Sen Chen
Tuberculosis is caused by Mycobacterium tuberculosis (Mtb) infection. Mtb is one of the oldest human pathogens, and evolves mechanisms implied in human evolution. The lungs are the first organ exposed to aerosol-transmitted Mtb during gaseous exchange. Therefore, the guards of the immune system in the lungs, such as macrophages (Mϕs) and dendritic cells (DCs), are the most important defense against Mtb infection. There have been several studies discussing the functions of Mϕs and DCs during Mtb infection, but the genome-wide pathways and networks are still incomplete...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27767027/accelerated-oral-nanomedicine-discovery-from-miniaturized-screening-to-clinical-production-exemplified-by-paediatric-hiv-nanotherapies
#12
Marco Giardiello, Neill J Liptrott, Tom O McDonald, Darren Moss, Marco Siccardi, Phil Martin, Darren Smith, Rohan Gurjar, Steve P Rannard, Andrew Owen
Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral...
October 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27759759/human-immunodeficiency-virus-in-institutionalized-elderly-people
#13
Milton Luiz Gorzoni, Sueli Luciano Pires, Lilian de Fátima Costa Faria, Márcia Regina Valadares Aguado, Miriam Carmen Santana
CONTEXT AND OBJECTIVE: A search in the SciELO and PubMed databases showed few studies on human immunodeficiency virus (HIV) positive individuals in long-term care institutions (LTCIs), thus prompting the present study. The aim of this study was to ascertain whether there were any HIV-positive individuals in LTCIs for the elderly. DESIGN AND SETTING: Cross-sectional study in which the Hospital Infection Control Committee (HICC) of a 405-bed LTCI was consulted. METHODS: The medical records of 405 individuals interned in the LTCI who had been tested for HIV infection were requested for analysis of the following variables: [1] age and gender; [2] length of stay at LTCI (months); [3] causes and diagnoses on admission to LTCI according to International Classification of Diseases, 10th edition; [4] date of HIV diagnosis; [5] seropositivity for syphilis and hepatitis B and C viruses; [6] medications used at last prescription in medical file; and [7] mean CD4 lymphocyte count based on: total lymphocyte count/6 and total lymphocyte count x 0...
October 13, 2016: São Paulo Medical Journal, Revista Paulista de Medicina
https://www.readbyqxmd.com/read/27749514/therapeutic-drug-monitoring-of-lopinavir-in-hiv-infected-children-on-second-line-antiretroviral-therapy-in-asia
#14
Linda Aurpibul, Sirinya Teerananchai, Wasana Prasitsuebsai, Tavitiya Sudjaritruk, Pope Kosalaraksa, Nia Kurniati, Khanh Huu Truong, Viet Chau Do, Lam Van Nguyen, Kulkanya Chokephaibulkit, Thida Singtoroj, Stephen J Kerr
BACKGROUND: Failure rates of second-line boosted protease inhibitor antiretroviral therapy regimens in children rise over time. Therapeutic drug monitoring can contribute to assessments of adherence. The authors assessed the performance characteristics of the US DHHS-recommended lopinavir (LPV) concentration of 1.0 mg/L for predicting virologic failure (VF) and intermediate- to high-level LPV resistance in Asian children. METHODS: LPV concentration, HIV RNA level, and adherence data from study participants in Thailand, Vietnam, and Indonesia receiving second-line LPV-based ART and followed for ≥24 weeks were analyzed...
December 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27747685/dosing-recommendations-of-aripiprazole-depot-with-strong-cytochrome-p450-3a4-inhibitors-a-relapse-risk
#15
Martina Hahn, Sibylle C Roll
A 50-year-old male patient with comorbid human immunodeficiency virus developed a relapse of bipolar disorder after a switch from oral aripiprazole 10 mg/day to intramuscular aripiprazole depot 200 mg every 28 days plus oral aripiprazole 5 mg/day. The patient was concomitantly taking lopinavir, saquinavir, ritonavir, silybum marianum extract, and omeprazole. Only 1 week after the switch, the patient developed mood swings, irritability, depressive mood, and lack of drive. The oral aripiprazole was increased again to stabilize the patient...
December 2016: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/27746450/therapeutic-drug-monitoring-of-anti-human-immunodeficiency-virus-drugs-in-a-patient-with-short-bowel-syndrome
#16
Motoko Ikuma, Dai Watanabe, Hiroki Yagura, Misa Ashida, Masaaki Takahashi, Masaaki Shibata, Tadafumi Asaoka, Munehiro Yoshino, Tomoko Uehira, Wataru Sugiura, Takuma Shirasaka
An elderly woman with human immunodeficiency virus-1 infection developed short bowel syndrome as a result of extensive intestinal resection. Considering the possibility of poor absorption of antiretroviral drugs (ARVs), therapeutic drug monitoring (TDM) was performed. A single-dose test of 6 ARVs (darunavir, ritonavir, lopinavir, etravirine, maraviroc, and raltegravir) did not provide information on the appropriate ARV, and repeated TDM under continuous antiretroviral therapy resulted in viral suppression below 50 copies/mL, which was considered to be treatment success...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27740537/hyperlipidaemia-in-hiv-infected-patients-on-lopinavir-ritonavir-monotherapy-in-resource-limited-settings
#17
Mitch M Matoga, Mina C Hosseinipour, Evgenia Aga, Heather J Ribaudo, Nagalingeswaran Kumarasamy, John Bartlett, Michael D Hughes
BACKGROUND: Cardiovascular disease (CVD) is an emerging concern for HIV-infected patients. Hyperlipidemia is a risk factor for CVD and a complication of protease-inhibitor-based antiretroviral therapy, but little is known about its incidence and risk factors in treated patients in resource-limited settings (RLS). METHODS: We conducted a secondary analysis of ACTG A5230 trial in which HIV-infected adults from India, Malawi, Tanzania, Thailand and South Africa, with virologic relapse on first line therapy were initiated on lopinavir/ritonavir (LPV/r) monotherapy...
October 14, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27708251/an-open-label-randomized-study-of-the-impact-on-insulin-sensitivity-lipid-profile-and-vascular-inflammation-by-treatment-with-lopinavir-ritonavir-or-raltegravir-in-hiv-negative-male-volunteers
#18
Paul Randell, Akil Jackson, Ana Milinkovic, Marta Boffito, Graeme Moyle
BACKGROUND: We aimed to measure the effect of raltegravir (RAL) on insulin sensitivity and surrogates of CV risk in healthy HIV-seronegative volunteers compared to that of lopinavir/r (LPV/r), a positive control. METHODS: An open label, two phase crossover study in HIV-negative male subjects randomized 1:1 to receive either 2 weeks of LPV/r followed by a two week washout period and two weeks of RAL, or RAL initially followed by LPV/r. A hyperinsulinaemic euglycaemic clamp was performed prior to and following each 2-week dosing phase...
October 6, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27704010/human-immunodeficiency-virus-1-sequence-changes-and-drug-resistance-mutation-among-virologic-failures-of-lopinavir-ritonavir-monotherapy-aids-clinical-trials-group-protocol-a5230
#19
Saran Vardhanabhuti, David Katzenstein, John Bartlett, Nagalingeswaran Kumarasamy, Carole L Wallis
Background.  The mechanism of virologic failure (VF) of lopinavir/ritonavir (LPV/r) monotherapy is not well understood. We assessed sequence changes in human immunodeficiency virus-1 reverse-transcriptase (RT) and protease (PR) regions. Methods.  Human immunodeficiency virus-1 pol sequences from 34 participants who failed second-line LPV/r monotherapy were obtained at study entry (SE) and VF. Sequence changes were evaluated using phylogenetic analysis and hamming distance. Results.  Human immunodeficiency virus-1 sequence change was higher over drug resistance mutation (DRM) sites (median genetic distance, 2...
September 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27665573/evaluation-of-concomitant-antiretrovirals-and-cyp2c9-cyp2c19-polymorphisms-on-the-pharmacokinetics-of-etravirine
#20
Bruce Green, Herta Crauwels, Thomas N Kakuda, Simon Vanveggel, Anne Brochot
BACKGROUND: Etravirine is a non-nucleoside reverse transcriptase inhibitor indicated in combination with other antiretrovirals for treatment-experienced HIV patients ≥6 years of age. Etravirine is primarily metabolized by cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A. This analysis determined the impact of concomitant antiretrovirals and CYP2C9/CYP2C19 phenotype on the pharmacokinetics of etravirine. METHODS: We used 4728 plasma concentrations from 817 adult subjects collected from four clinical studies to develop the population pharmacokinetic model...
September 24, 2016: Clinical Pharmacokinetics
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