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Inhibitors integrase in childrens

Manuel González-González, Consuelo Correa-Sierra, Katherine Hermida-Álava, Ana Machado-Díaz, L Fernando Gómez-Andrade, Martha Castillo-Segovia, C Lissette Pérez-Santos, Vivian Kourí-Cardellá
Background The international recommendations of antiretroviral treatment include resistance tests to guide the treatment regimen in each patient, which is not available on a regular basis in Ecuador. Aim To describe mutations that confer resistance to antiretrovirals in a population of Ecuadorian patients. Methods Plasma samples from 101 HIV-1 patients with failure to antiretroviral therapy, divided into 15 children and 86 adults, were studied with the GS Junior (Roche) and the sequences were analyzed with the DeepChek program...
2018: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
Joseph Fokam, Maria C Bellocchi, Daniele Armenia, Aubin J Nanfack, Luca Carioti, Fabio Continenza, Desire Takou, Edith S Temgoua, Charlotte Tangimpundu, Judith N Torimiro, Paul N Koki, Charles N Fokunang, Giulia Cappelli, Alexis Ndjolo, Vittorio Colizzi, Francesca Ceccherini-Silberstein, Carlo-Federico Perno, Maria M Santoro
With limited and low-genetic barrier drugs used for the prevention of mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa, vertically transmitted HIV-1 drug-resistance (HIVDR) is concerning and might prompt optimal pediatric strategies.The aim of this study was to ascertain HIVDR and viral-tropism in majority and minority populations among Cameroonian vertically infected children.A comparative analysis among 18 HIV-infected children (7 from PMTCT-exposed mothers and 11 from mothers without PMTCT-exposure) was performed...
March 2018: Medicine (Baltimore)
Eugenia Bruzzese, Andrea Lo Vecchio, Andrea Smarrazzo, Orsola Tambaro, Giulia Palmiero, Giovanni Bonadies, Alfredo Guarino
BACKGROUND: Treatment of HIV infection in adolescents is challenging due to long duration of therapy and poor adherence. Recently, the integrase strand transfer inhibitor dolutegravir (DTG) has been approved for the use in adolescents with HIV, but evidence in clinical practice is very limited. METHODS: We describe six cases of HIV-infected children/adolescents successfully treated with DTG-based regimen. Data relative to children/adolescents managed at the Referral Center for Pediatric HIV/AIDS of the University of Naples were reviewed...
March 20, 2018: Italian Journal of Pediatrics
Michael R Jordan, Martina Penazzato, Amandine Cournil, Adolfo Vubil, Ilesh Jani, Gillian Hunt, Sergio Carmona, Gugu Maphalala, Nobuhle Mthethwa, Christine Watera, Pontiano Kaleebu, Christine Chakanyuka Musanhu, Sekesai Mtapuri-Zinyowera, Janet Dzangare, Martine Peeters, Chunfu Yang, Neil Parkin, Silvia Bertagnolio
Background: Programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) have been scaled up in many low- and middle-income countries. However, HIV drug resistance (HIVDR) data among HIV-1-infected young children remain limited. Methods: Surveys of pretreatment HIVDR among children aged <18 months who were diagnosed with HIV through early infant diagnosis were conducted in 5 sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization (WHO) guidance...
November 29, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Ragna S Boerma, Torsak Bunupuradah, Dorothy Dow, Joseph Fokam, Azar Kariminia, Dara Lehman, Cissy Kityo, Victor Musiime, Paul Palumbo, Annelot Schoffelen, Sam Sophan, Brian Zanoni, Tobias F Rinke de Wit, Job C J Calis, Kim C E Sigaloff
INTRODUCTION: The number of HIV-infected children and adolescents requiring second-line antiretroviral treatment (ART) is increasing in low- and middle-income countries (LMIC). However, the effectiveness of paediatric second-line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second-line ART outcomes for children and assessed the need for paediatric third-line ART. METHODS: We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second-line ART in LMIC, contacting the corresponding study groups and including patient-level data on virologic and clinical outcomes...
September 15, 2017: Journal of the International AIDS Society
Walter Dehority, Jacobo Abadi, Andrew Wiznia, Rolando M Viani
Resistance to antiretroviral drugs is an increasingly prevalent challenge affecting both the adult and pediatric HIV-infected populations. Though data on the safety, pharmacokinetics, and efficacy of newer antiretroviral agents in children typically lags behind adult data, newer agents are becoming available for use in HIV-infected children who are failing to respond to or are experiencing toxicities with traditional antiretroviral regimens. Integrase strand transfer inhibitors are one such new class of antiretrovirals...
September 2015: Drugs
(no author information available yet)
The first integrase inhibitor to be approved for children; antiretroviral effect similar to that observed in adults in treatment failure; no first-line evaluation.
September 2014: Prescrire International
Andrea C Tricco, Jesmin Antony, Veroniki A Angeliki, Huda Ashoor, Brian Hutton, Brenda R Hemmelgarn, David Moher, Yaron Finkelstein, Kevin Gough, Sharon E Straus
BACKGROUND: Antiretroviral therapy reduces mother-to-child transmission of human immunodeficiency virus (HIV) during pregnancy, delivery, and breastfeeding. However, these agents have been associated with preterm birth, anemia and low birth weight. We aim to evaluate the comparative safety and effectiveness of the use of antiretroviral drugs among HIV-infected women and the effects on their infants and children through a systematic review and network meta-analysis. METHODS/DESIGN: Studies examining the effects of six antiretroviral drug classes (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion inhibitors, co-receptor inhibitors) administered to HIV-infected pregnant women will be included...
2014: Systematic Reviews
Mario Regazzi, Anna Cristina Carvalho, Paola Villani, Alberto Matteelli
Tuberculosis (TB) and HIV continue to be two of the major causes of morbidity and mortality in the world, and together are responsible for the death of millions of people every year. There is overwhelming evidence to recommend that patients with TB and HIV co-infection should receive concomitant therapy of both conditions regardless of the CD4 cell count level. The principles for treatment of active TB disease in HIV-infected patients are the same as in HIV-uninfected patients. However, concomitant treatment of both conditions is complex, mainly due to significant drug-drug interactions between TB and HIV drugs...
June 2014: Clinical Pharmacokinetics
Elizabeth G Rhee, Matthew L Rizk, Diana M Brainard, Isaias N Gendrano, Bo Jin, Larissa A Wenning, John A Wagner, Marian Iwamoto
BACKGROUND: Raltegravir is an HIV-1 integrase inhibitor approved for use in adults, children and infants ≥4 weeks of age. As alternatives to the original film-coated tablet, a chewable ethylcellulose (EC) tablet and oral granules for suspension (GFS) have been developed for use in children. The purpose of this study was to evaluate these formulations in adults prior to use in paediatric studies. METHODS: This open-label, 4-period, randomized, crossover study investigated the safety, tolerability and pharmacokinetics of raltegravir paediatric formulations and the effect of a high-fat meal on EC tablet pharmacokinetics in healthy adults...
2014: Antiviral Therapy
Kajal B Larson, Jennifer R King, Edward P Acosta
Raltegravir was the first HIV integrase strand-transfer inhibitor to be approved by the US FDA, in October 2007, for the treatment of HIV-1 infection in combination with other antiretroviral agents. Raltegravir can be used in treatment-naïve and -experienced patients, as well as for the treatment of multidrug-resistant infection. Raltegravir exists in two formulations: a film-coated tablet administered orally at 400 mg twice daily, and a chewable tablet administered orally at 300 mg twice daily. In 2011, raltegravir was also approved for the treatment of children and adolescents, ages 2-18 years...
2013: Adolescent Health, Medicine and Therapeutics
Ingo Stock
Integrase inhibitors are a promising new group of antiretroviral drugs that suppress the integrase yielded by human immunodeficiency viruses (HIV) via inhibiting the ,,integration" of the viral deoxyribonucleic acid (DNA) into the hosts' DNA genome. In 2007, raltegravir was the first integrase inhibitor that has been approved for the treatment of HIV-1 infections in antiretroviral-pretreated (-experienced) and antiretroviral-naive patients. Recently, elvitegravir, as a fixed coformulation with cobicistat, tenofovir und emtricitabine, has been approved for the treatment of HIV-1-infected antiretroviral-naive patients...
December 2013: Medizinische Monatsschrift Für Pharmazeuten
Caroline M Perry
Raltegravir (ISENTRESS(®)) is an HIV-1 integrase strand transfer inhibitor that is well established as a component of highly active antiretroviral therapy regimens for the treatment of adults with HIV-1 infection, and has recently been approved for the treatment of HIV-1-infected children and adolescents aged 2-18 years. A new chewable formulation has been introduced and results of a pharmacokinetic study have led to the establishment of dosages for this formulation for children. In a phase I/II, open-label, multicentre, clinical trial, raltegravir (administered as the chewable or the film-coated tablet) in combination with optimized background antiretroviral therapy was an effective treatment for treatment-experienced children and adolescents with HIV-1 infection, in terms of virologic measures of efficacy (i...
February 2014: Paediatric Drugs
R Chris Rathbun, Staci M Lockhart, Misty M Miller, Michelle D Liedtke
OBJECTIVE: To review the pharmacology, safety, and efficacy of dolutegravir, an integrase strand-transfer inhibitor (INSTI), and to discuss its role in the treatment of HIV-1-infected patients. DATA SOURCES: PubMed articles indexed through August 2013 were identified using the search terms S/GSK1349572, dolutegravir, and integrase inhibitor. Information was also identified from the package insert, cited publication references, professional meeting abstracts, and the ClinicalTrials...
March 2014: Annals of Pharmacotherapy
Nathan Ford, Charles Flexner, Stefano Vella, David Ripin, Marco Vitoria
PURPOSE OF REVIEW: The review reflects on opportunities and challenges for HIV treatment optimization for the next 5 years. RECENT FINDINGS: Considering all currently available options, the fixed-dose combination of tenofovir + lamivudine (or emtricitabine) + efavirenz is considered as the best option for first-line treatment for the short to medium term. Second-line therapy will likely continue to be comprised of a boosted protease inhibitor in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), with potential for combining with integrase inhibitors...
November 2013: Current Opinion in HIV and AIDS
Janice Soo Fern Lee, Alexandra Calmy, Isabelle Andrieux-Meyer, Nathan Ford
Integrase inhibitors represent an important new class of antiretroviral drugs. Elvitegravir, the second available integrase inhibitor to be submitted for regulatory approval appears to be a promising once-daily agent when combined with other antiretroviral drugs. Elvitegravir has demonstrated good efficacy and safety, with minimal side effects and no specific requirements in terms of laboratory monitoring. In addition, elvitegravir is available as a fixed-dose combination. However, the drug requires boosting and this leads to a number of drug-drug interactions and necessary dose adjustment when dosing with certain drugs, including dose reduction in the presence of atazanavir, lopinavir, rifabutin, and ketoconazole, and dose increase for ethinyl estradiol when co-administered with boosted elvitegravir...
2012: HIV/AIDS: Research and Palliative Care
Brian S Eley, Tammy Meyers
WHO antiretroviral treatment guidelines for HIV-infected children have influenced the design of treatment programmes in resource-limited settings. This review analyses the latest WHO first- and second-line regimen recommendations. The recommendation to use lopinavir/ritonavir-containing first-line regimens in young children with prior non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure is based on good quality evidence. Recent research suggests that lopinavir/ritonavir-containing first-line regimens should be extended to all young children, irrespective of prior NNRTI exposure...
October 1, 2011: Paediatric Drugs
Yoshiki Katsumi, Tomoko Iehara, Mitsuru Miyachi, Shigeki Yagyu, Satoko Tsubai-Shimizu, Ken Kikuchi, Shinichi Tamura, Yasumichi Kuwahara, Kunihiko Tsuchiya, Hiroshi Kuroda, Tohru Sugimoto, Peter J Houghton, Hajime Hosoi
Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of young children. MRT is characterized by inactivation of integrase interactor 1 (INI1). Cyclin-dependent kinase 4 (CDK4), which acts downstream of INI1, is required for the proliferation of MRT cells. Here we investigated the effects of PD 0332991 (PD), a potent inhibitor of CDK4, against five human MRT cell lines (MP-MRT-AN, KP-MRT-RY, G401, KP-MRT-NS, KP-MRT-YM). In all of the cell lines except KP-MRT-YM, PD inhibited cell proliferation >50%, (IC(50) values 0...
September 16, 2011: Biochemical and Biophysical Research Communications
Amy Slogrove, Helena Rabie, Mark Cotton
INTRODUCTION: HIV-1 infection is a major problem for children in lower income countries. The benefit of early antiretroviral (ARV) therapy started within 12 weeks of life is well documented. Although the development of new drug classes give alternative options for highly treatment experienced patients there is inadequate pharmacokinetic knowledge regarding the already established ARV classes in infants and children. Also, there are many practical challenges to administering these agents to children...
April 2011: Infectious Disorders Drug Targets
Joshua D Courter, Colleen J Teevan, Michael H Li, Jennifer E Girotto, Juan C Salazar
The worldwide emergence of multidrug-resistant human immunodeficiency virus (HIV)-1 strains has the driven the development of new antiretroviral (ARV) agents. Over the past 5 years, HIV-entry and integrase inhibitor ARVs, as well as improved non-nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), have become available for treatment. It is important to assess how these new ARVs might be most judiciously used, paying close attention to viral susceptibility patterns, pharmacodynamic parameters, and the likelihood that patients will adhere to their therapy...
October 5, 2010: Therapeutics and Clinical Risk Management
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