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raltegravir

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https://www.readbyqxmd.com/read/29145807/durability-of-switch-regimens-based-on-rilpivirine-or-on-integrase-inhibitors-both-in-association-with-tenofovir-and-emtricitabine-in-hiv-infected-virologically-suppressed-patients
#1
Nicola Gianotti, Andrea Poli, Silvia Nozza, Laura Galli, Nadia Galizzi, Marco Ripa, Marco Merli, Alessia Carbone, Vincenzo Spagnuolo, Adriano Lazzarin, Antonella Castagna
BACKGROUND: Switch strategies based on rilpivirine/tenofovir/emtricitabine or on an integrase inhibitor (InSTI) plus tenofovir/emtricitabine have never been compared in randomized clinical trials. The main aim of the study was to investigate the durability of these two switch regimens in virologically suppressed, HIV-infected patients. METHODS: Retrospective analysis of patients who started rilpivirine or an InSTI (both with tenofovir and emtricitabine) with <50 HIV-RNA copies/mL and had at least one HIV-RNA assessed while receiving the study regimen...
November 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29140932/characteristics-of-treatment-experienced-hiv-infected-african-children-and-adolescents-initiating-darunavir-and-or-etravirine-based-antiretroviral-treatment
#2
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/29112076/virologic-suppression-and-cd4-cell-count-recovery-after-initiation-of-raltegravir-or-efavirenz-containing-hiv-treatment-regimens
#3
Jessie K Edwards, Stephen R Cole, H Irene Hall, W Christopher Mathews, Richard D Moore, Michael J Mugavero, Joseph J Eron
OBJECTIVE: To explore the effectiveness of raltegravir-based antiretroviral therapy (ART) on treatment response among ART-naive patients seeking routine clinical care. DESIGN: Cohort study of adults enrolled in HIV care in the United States. METHODS: We compared virologic suppression and CD4 cell count recovery over a 2.5 year period after initiation of an ART regimen containing raltegravir or efavirenz using observational data from a US clinical cohort, generalized to the US population of people with diagnosed HIV...
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
#4
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/29106584/plasma-trough-concentrations-of-antiretrovirals-in-hiv-infected-persons-treated-with-direct-acting-antiviral-agents-for-hepatitis-c-in-the-real-world
#5
Massimo Tempestilli, Gabriele Fabbri, Ilaria Mastrorosa, Laura Timelli, Stefania Notari, Rita Bellagamba, Raffaella Libertone, Federico Lupi, Mauro Zaccarelli, Andrea Antinori, Chiara Agrati, Adriana Ammassari
Background: Possible drug-drug interactions (DDIs) between antiretrovirals (ARVs) and direct-acting antiviral agents (DAAs) are of some concern. Objectives: To investigate ARV plasma trough concentrations (Ctrough) before and during DAAs in patients treated in the real world. Methods: Single-centre, prospective, observational study including HIV/HCV coinfected persons undergoing DAA treatment. Self-reported adherence was assessed and ARVs Ctrough measured by HPLC-UV...
November 2, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29098203/prospective-analysis-of-lipid-composition-changes-with-antiretroviral-therapy-and-immune-activation-in-persons-living-with-hiv
#6
Martha A Belury, Emily Bowman, Janelle Gabriel, Brandon Snyder, Manjusha Kulkarni, Marilly Palettas, Xiaokui Mo, Jordan E Lake, David Zidar, Scott F Sieg, Benigno Rodriguez, Martin P Playford, Adriana Andrade, Daniel R Kuritzkes, Nehal N Mehta, Michael M Lederman, Nicholas T Funderburg
Background: Lipid profiles are altered by HIV infection and antiretroviral therapy (ART). Among HIV-uninfected (HIV-) populations the concentrations of various lipid classes (ie, lyso-phosphatidylcholine, LPC) and their saturated (SaFA), mono-unsaturated (MUFA), and polyunsaturated fatty acid (PUFA) composition are related to cardiometabolic disease risk. Associations between changes in the lipidome and immune activation in HIV-infected (HIV+) individuals beginning ART have not been described...
2017: Pathogens & Immunity
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
#7
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/29077949/incorporation-of-aptamers-in-the-terminal-loop-of-shrnas-yields-an-effective-and-novel-combinatorial-targeting-strategy
#8
Ka Ming Pang, Daniela Castanotto, Haitang Li, Lisa Scherer, John J Rossi
Gene therapy by engineering patient's own blood cells to confer HIV resistance can potentially lead to a functional cure for AIDS. Toward this goal, we have previously developed an anti-HIV lentivirus vector that deploys a combination of shRNA, ribozyme and RNA decoy. To further improve this therapeutic vector against viral escape, we sought an additional reagent to target HIV integrase. Here, we report the development of a new strategy for selection and expression of aptamer for gene therapy. We developed a SELEX protocol (multi-tag SELEX) for selecting RNA aptamers against proteins with low solubility or stability, such as integrase...
October 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29077766/peripheral-blood-hiv-1-dna-dynamics-in-antiretroviral-treated-hiv-hcv-co-infected-patients-receiving-directly-acting-antivirals
#9
Gabriella Rozera, Gabriele Fabbri, Patrizia Lorenzini, Ilaria Mastrorosa, Laura Timelli, Mauro Zaccarelli, Alessandra Amendola, Alessandra Vergori, Maria Maddalena Plazzi, Stefania Cicalini, Andrea Antinori, Maria Rosaria Capobianchi, Isabella Abbate, Adriana Ammassari
BACKGROUND: Aim was to determine the dynamics of peripheral blood mononuclear cells (PBMC)- associated total HIV-1 DNA in successfully ART-treated HIV/HCV co-infected patients receiving DAA treatment and to explore possible virological hypotheses underlying the phenomenon. METHODS: Longitudinal, single-centre study measuring total HIV-1 DNA before the start of DAA, at the end of treatment (EOT), and 3 months after treatment. Univariable and multivariable analyses were used to assess factors associated with HIV-1 DNA increase ≥0...
2017: PloS One
https://www.readbyqxmd.com/read/29071467/raltegravir-once-daily-tablet-a-review-in-hiv-1-infection
#10
Emma D Deeks
A once-daily tablet formulation (Isentress(®) HD; Isentress(®) 600 mg) of the integrase strand transfer inhibitor raltegravir is now available for the treatment of HIV-1 infection. The 600 mg tablet has improved bioavailability versus the existing twice-daily 400 mg tablet (due, at least in part, to differences in tablet dissolution) and the recommended dosage is 1200 mg (i.e. two 600 mg tablets) once daily. In combination with emtricitabine/tenofovir disoproxil fumarate in treatment-naïve adults, once-daily raltegravir 1200 mg provided virological suppression non-inferior to that seen with twice-daily raltegravir 400 mg over 48 and 96 weeks in the phase 3 ONCEMRK trial...
October 2017: Drugs
https://www.readbyqxmd.com/read/29070877/probing-resistance-mutations-in-retroviral-integrases-by-direct-measurement-of-dolutegravir-fluorescence
#11
Eloïse Thierry, Samuel Lebourgeois, Françoise Simon, Olivier Delelis, Eric Deprez
FDA-approved integrase strand transfer inhibitors (raltegravir, elvitegravir and dolutegravir) efficiently inhibit HIV-1 replication. Here, we present fluorescence properties of these inhibitors. Dolutegravir displays an excitation mode particularly dependent on Mg(2+) chelation, allowing to directly probe its Mg(2+)-dependent binding to the prototype foamy virus (PFV) integrase. Dolutegravir-binding studied by both its fluorescence anisotropy and subsequent emission enhancement, strictly requires a preformed integrase/DNA complex, the ten terminal base pairs from the 3'-end of the DNA reactive strand being crucial to optimize dolutegravir-binding in the context of the ternary complex...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29049331/hiv-dynamics-linked-to-memory-cd4-t-cell-homeostasis
#12
John M Murray, John Zaunders, Sean Emery, David A Cooper, William J Hey-Nguyen, Kersten K Koelsch, Anthony D Kelleher
The dynamics of latent HIV is linked to infection and clearance of resting memory CD4+ T cells. Infection also resides within activated, non-dividing memory cells and can be impacted by antigen-driven and homeostatic proliferation despite suppressive antiretroviral therapy (ART). We investigated whether plasma viral level (pVL) and HIV DNA dynamics could be explained by HIV's impact on memory CD4+ T cell homeostasis. Median total, 2-LTR and integrated HIV DNA levels per μL of peripheral blood, for 8 primary (PHI) and 8 chronic HIV infected (CHI) individuals enrolled on a raltegravir (RAL) based regimen, exhibited greatest changes over the 1st year of ART...
2017: PloS One
https://www.readbyqxmd.com/read/29045448/interferon-free-therapy-with-direct-acting-antivirals-for-hcv-hiv-1-co-infected-japanese-patients-with-inherited-bleeding-disorders
#13
Haruka Uemura, Kunihisa Tsukada, Daisuke Mizushima, Takahiro Aoki, Koji Watanabe, Ei Kinai, Katsuji Teruya, Hiroyuki Gatanaga, Yoshimi Kikuchi, Masaya Sugiyama, Masashi Mizokami, Shinichi Oka
INTRODUCTION: Almost 30 years ago, about 30% of Japanese hemophiliacs became infected with HIV-1 and hepatitis C virus (HCV) after receiving contaminated blood products. While several studies have reported the high efficacy and safety of direct acting antivirals (DAA) in HIV-1 co-infected patients, such data are limited in hemophiliacs. METHODS: We conducted a single-center, open-label study involving 27 Japanese patients (median age; 45 years) with inherited bleeding disorders who were co-infected with HCV/HIV-1...
2017: PloS One
https://www.readbyqxmd.com/read/29039686/prevention-and-treatment-of-hiv-infection-in-neonates-evidence-base-for-existing-who-dosing-recommendations-and-implementation-considerations
#14
Diana F Clarke, Martina Penazzato, Edmund Capparelli, Tim R Cressey, George Siberry, Nandita Sugandhi, Mark Mirochnick
Antiretroviral drugs are used in neonates for prevention and treatment of HIV infection. Use of antiretrovirals to prevent perinatal HIV transmission is well established. Early identification of neonates infected with HIV and rapid initiation of combination antiretroviral treatment during the neonatal period is now recommended by WHO and DHHS. However, few antiretrovirals are available in formulations suitable for neonates and there are limited safety and pharmacokinetic data for most antiretrovirals in neonates...
October 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29021409/hiv-1-viral-load-and-resistance-in-genital-secretions-in-patients-taking-protease-inhibitor-based-second-line-therapy-in-africa
#15
Anne Hoppe, Marina Giuliano, Abbas Lugemwa, Jennifer A Thompson, Marco Floridia, Ann S Walker, Ismail Senoga, Mary C Abwola, Maria F Pirillo, Cissy M Kityo, Alejandro Arenas-Pinto, Nicholas I Paton
BACKGROUND: HIV is transmitted primarily through sexual intercourse, and the objective of this study was therefore to assess whether there is occult viral replication and resistance in genital secretions in patients on protease inhibitor (PI)-based second-line therapy. METHODS: HIV-infected adults taking ritonavir-boosted lopinavir with either two NRTIs, raltegravir, or as monotherapy for 96 weeks were enrolled at seven clinical sites in Uganda. Viral load (VL) was measured in cervico-vaginal secretions or semen and in a corresponding plasma sample...
October 11, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28994443/role-of-raltegravir-in-patients-co-infected-with-hiv-and-hcv-in-the-era-of-direct-antiviral-agents
#16
Lucia Taramasso, Giovanni Cenderello, Niccolò Riccardi, Simone Tunesi, Antonio Di Biagio
Integrase strand transfer inhibitors (INSTIs) are the preferred third agent in first-line antiretroviral therapies. Raltegravir (RAL) was the first INSTI to be approved and used in naïve and experienced patients. Due to its good tolerability and low side effects, RAL has been largely used also in hepatitis co-infected patients. Many years of experience in RAL use now allow literature evidence to be gathered on its safety in HIV/HCV-co-infected patients pre, during and post direct acting agents (DAA) treatment, at all possible stages...
October 10, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28984429/incidence-of-cancer-and-overall-risk-of-mortality-in-individuals-treated-with-raltegravir-based-and-non-raltegravir-based-combination-antiretroviral-therapy-regimens
#17
A Cozzi-Lepri, R Zangerle, L Machala, K Zilmer, M Ristola, C Pradier, O Kirk, H Sambatakou, G Fätkenheuer, I Yust, P Schmid, M Gottfredsson, I Khromova, D Jilich, R Flisiak, J Smidt, B Rozentale, R Radoi, M H Losso, J D Lundgren, A Mocroft
OBJECTIVES: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. METHODS: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007...
October 6, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28969567/long-term-treatment-with-raltegravir-is-associated-with-lowering-triglycerides-and-platelets-count-in-the-older-hiv-population-results-from-the-ral-age-study
#18
Paolo Pavone, Noemi Giustini, Caterina Fimiani, Francesca Paoletti, Mario Falciano, Alessandra Salotti, Fiorella Di Sora, Samir Al Moghazi, Ivano Mezzaroma, Vincenzo Vullo, Gabriella D'Ettorre
BACKGROUND: Raltegravir (RAL) is considered one of the better-tolerated antiretroviral medications, due to limited side effects and minimal drug-drug interactions. Matherials and Methods: We retrospectively evaluated 96 HIV+, over 60 years old, experienced patients who had switched from any antiretroviral drug to raltegravir-based nuc-sparing or standard nucleoside-backbone regimens. RESULTS: The median age of the patients was 66 years (IQR 10.5) (77 M, 19 F); the median time horizon of follow-up was 4 years (IQR 5)...
September 27, 2017: Current HIV Research
https://www.readbyqxmd.com/read/28968669/human-immunodeficiency-virus-type-1-drug-resistance-mutations-update
#19
Robert W Shafer
As treatment options coalesce around a smaller number of antiretroviral drugs (ARVs), data are emerging on the drug resistance mutations (DRMs) selected by the most widely used ARVs and on the impact of these DRMs on ARV susceptibility and virological response to first- and later-line treatment regimens. Recent studies have described the DRMs that emerge in patients receiving tenofovir prodrugs, the nonnucleoside reverse transcriptase inhibitors efavirenz and rilpivirine, ritonavir-boosted lopinavir, and the integrase inhibitors raltegravir and elvitegravir...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28961979/penetration-and-antiviral-efficacy-of-total-and-unbound-maraviroc-raltegravir-and-rilpivirine-in-both-female-and-male-genital-fluids-from-hiv-positive-patients-receiving-regimens-containing-these-antiretrovirals
#20
Minh P Lê, Linda Belarbi, Marie-Laure Chaix, Emmanuel Dulioust, Nadia Mahjoub, Dominique Salmon, Jean-Paul Viard, Claudine Duvivier, Gilles Peytavin, Odile Launay, Jade Ghosn
Background: Sub-optimal penetration of antiretroviral drugs in genital compartments might promote local HIV persistence and increase the risk of HIV transmission. Objectives: To describe the penetration of maraviroc, raltegravir, raltegravir glucuronide and rilpivirine in seminal plasma and cervico-vaginal secretions (CVS) and to assess local antiretroviral efficacy in HIV-1-positive patients. Methods: This was a prospective, multicentre study...
November 1, 2017: Journal of Antimicrobial Chemotherapy
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