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Dolutegravir in childrens

Pierre Frange, Véronique Avettand-Fenoel, Florence Veber, Stéphane Blanche, Marie-Laure Chaix
Objectives: To describe the prevalence of transmitted drug resistance (TDR) among 84 children newly diagnosed with HIV in France in 2006-17. Methods: HIV-1 resistance-associated mutations (RAMs) were characterized using both the 2009 Stanford list of mutations and the 2017 French National Agency for AIDS Research (ANRS) algorithm. A genotypic susceptibility score (GSS) was estimated for each first-line recommended ART combination. Results: Patients were mainly infected through mother-to-child transmission (MTCT) (73/84; 86...
May 29, 2018: Journal of Antimicrobial Chemotherapy
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
Martina Penazzato, Claudia Palladino, Nandita Sugandhi
PURPOSE OF REVIEW: Initiatives are in place to reach super-fast targets by 2018 for paediatric patients living with HIV. However, these efforts are unlikely to be successful until better paediatric antiretrovirals and treatment strategies are available. This commentary reviews the specific features, challenges, and recent developments in paediatric HIV treatment to determine optimal regimen sequencing and use of available drug options. It also outlines a medium and long-term vision for treatment optimization as endorsed by the paediatric antiretroviral drug optimization group...
July 2017: Current Opinion in HIV and AIDS
Amy L Slogrove, Polly Clayden, Elaine J Abrams
PURPOSE OF REVIEW: As optimized antiretroviral therapy (ART) regimens are prepared for introduction in low-income and middle-income countries (LMIC), we consider the current evidence related to dosing, efficacy and safety during pregnancy and breastfeeding of next-generation first-line and second-line ART regimens proposed for imminent introduction in the global marketplace. RECENT FINDINGS: Pregnancy pharmacokinetic considerations include potentially insufficient efavirenz exposure if dosed at 400 mg/day, the need for twice daily darunavir dosing and the paucity of data related to tenofovir alafenamide and dolutegravir dosing, safety and efficacy...
July 2017: Current Opinion in HIV and AIDS
Rolando M Viani, Carmelita Alvero, Terry Fenton, Edward P Acosta, Rohan Hazra, Ellen Townley, Debra Steimers, Sherene Min, Andrew Wiznia
OBJECTIVE: To assess the pharmacokinetics (PK), safety and efficacy of dolutegravir plus optimized background regimen in HIV-infected treatment-experienced adolescents. METHODS: Children older than 12 to younger than 18 years received dolutegravir weight-based fixed doses at approximately 1.0 mg/kg once daily in a phase I/II multicenter open label 48-week study. Intensive PK evaluation was done at steady state after dolutegravir was added to a failing regimen or started at the end of a treatment interruption...
November 2015: Pediatric Infectious Disease Journal
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
N Wagner, C A Wyler-Lazarevic, S Yerly, C Samer, G Peytavin, K M Posfay-Barbe, A Calmy, J Ambrosioni
The management of multidrug-resistant human immunodeficiency virus (MDR HIV) infections in children is particularly challenging due to the lack of experience with new drugs. Dolutegravir, combined with an optimized antiretroviral background therapy, is promising for the treatment of MDR HIV and has been approved recently for adults and adolescents. Data for children are extremely limited. We describe the efficacy, safety and plasmatic levels of a dolutegravir-based, complex active antiretroviral treatment regimen in a severely overweight 11-year-old child infected with an MDR HIV strain...
July 2015: New Microbes and New Infections
Nathan Ford, Zara Shubber, Anton Pozniak, Marco Vitoria, Meg Doherty, Catherine Kirby, Alexandra Calmy
INTRODUCTION: Efavirenz (EFV) is widely used for the treatment of antiretroviral-naive HIV-positive individuals, but there are concerns about the risk of adverse neuropsychiatric events. We systematically reviewed the safety of EFV in first-line therapy. METHODS: Four databases were searched until October 2014 for randomized trials comparing EFV against non-EFV-based regimens for the treatment of antiretroviral-naive HIV-positive adults and children. The primary outcome was drug discontinuation as a result of any adverse event...
August 1, 2015: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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
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
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