Elvitegravir in childrens

BACKGROUND: Integrase inhibitor (INSTI) with boosted darunavir (DRV/r), a regimen with a high-resistance barrier, avoiding NRTI toxicities, might be a switching option in children living with HIV (CLWHIV). METHODS: SMILE is a randomised non-inferiority trial evaluating safety and antiviral efficacy of once-daily INSTI + DRV/r vs. continuing on current standard-of-care (SOC) triple ART (2NRTI + boosted PI/NNRTI) in virologically-suppressed CLWHIV aged 6-18 years...

INTRODUCTION: Integrase strand transfer inhibitors (INSTIs), including raltegravir (RAL), dolutegravir (DTG), elvitegravir (EVG), bictegravir (BIC), and cabotegravir (CAB), are increasingly used given excellent data on their efficacy, effectiveness, and tolerability profile in adults, while data in children are accumulating. OBJECTIVE AND METHODS: To review the most recent evidence on the efficacy, effectiveness, safety, and resistance of INSTIs in children, a quick narrative review of the available literature data was performed using,the MEDLINE/PubMed and Scopus databases, including only English-language studies, published between 2009-2022...

Integrase strand transfer inhibitors (INSTIs) have improved the treatment of human immunodeficiency virus (HIV). There are currently four approved for use in treatment-naïve individuals living with HIV; these include first generation raltegravir, elvitegravir, and second generation dolutegravir and bictegravir. The most recent INSTI, cabotegravir, is approved for (1) treatment of HIV infection in adults to replace current antiretroviral therapy in individuals who maintain virologic suppression on a stable antiretroviral regimen without history of treatment failure and no known resistance to its components and (2) pre-exposure prophylaxis in individuals at risk of acquiring HIV-1 infection...

BACKGROUND: Although integrase inhibitor (INI)-based regimens are now the first-line choice for all people living with HIV, experience among children and adolescents is still scarce. We describe the characteristics and outcomes of a paediatric/adolescent cohort on INI-based ART. METHODS: Retrospective analysis of HIV-infected patients below 18 years of age who started an INI-based regimen from 2007 to 2019, enrolled in the Spanish National Adult (CoRIS) and Paediatric (CoRISpe) cohorts...

BACKGROUND: Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2-12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. METHODS: An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018...

Integrase strand-transfer inhibitors (INSTI) are the latest class of antiretrovirals registered in Mexico. They include raltegravir (RAL), elvitegravir/cobicistat (EVG/c), dolutegravir (DTG) and bictegravir (BIC). Along with international guidelines, Mexico adopted the use of INSTI about two years ago as initial antiretroviral therapy (ART). This is partially due to the increase in the pre-treatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI), mainly efavirenz (EFV). Furthermore, INSTI depict greater efficacy, safety and less drug-drug interactions than NNRTI and protease inhibitors (PI)...

BACKGROUND AND OBJECTIVE: Integrase strand transfer inhibitors (INSTIs) have become the preferred first-line antiretroviral therapy in adults. There is paucity of published data on their use in children outside of clinical trials, particularly long-term safety and tolerability. This study aimed to describe INSTI use including the number of, and reasons for INSTI discontinuation. METHODS: We conducted a retrospective cohort analysis by database and electronic record review of children aged under 18 years with perinatally acquired human immunodeficiency virus who started INSTI-based antiretroviral therapy between May 2009 and March 2018, in a single tertiary centre...

In spite of remarkable reduction in the number of children born with HIV due to antiretroviral therapy, concerns remain on the short- and long-term effects of antiretroviral drugs at the feto-placental unit. Cardio- and skeletal myopathies have been reported in children exposed to antiretroviral drugs prenatally. These conditions have also been described in perturbed placental transfer of l-carnitine, an essential co-factor in fatty acid oxidation. Due to limited fetal and placental synthesis, carnitine supply is maintained through the placental carnitine uptake from maternal blood by the organic cation/carnitine transporters OCTN1 and OCTN2 (SLC22A4 and SLC22A5, respectively)...

Approximately 2.1 million of the estimated 36 million infected with HIV are children or adolescents. International guidelines for HIV-1 Infection suggest starting antiretrovirals (ARV) at the moment of diagnosis. Many factors limit the optimization of antiretroviral therapy in children and adolescents: lack of pediatric formulations, poor adherence, metabolic and pharmacokinetic changes associated withnormal child development and puberty. Areas covered: Three integrase inhibitors are approved by the US Food and Drug Administration and by European Medical Agency for children and adolescents with HIV-1 infection...

BACKGROUND: The indisputable benefits of antiretroviral therapy (ART) in the reduction of mother-to-child-transmission of HIV have to be carefully balanced with the risks of embryo-fetal toxicities due to fetal exposure to maternal ART. The recent report of a potential safety signal with dolutegravir use in pregnancy and potential increased rate of neural tube defects has raised the question of a potential class effect for integrase strand inhibitors. To contribute real-world evidence, we evaluated data on pregnant women receiving raltegravir (RAL) or elvitegravir (EVG) in the United Kingdom and Ireland...

OBJECTIVE: To evaluate elvitegravir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples after delivery. DESIGN: Nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and their children in the United States. METHODS: Intensive steady-state 24-h pharmacokinetic profiles after 150 mg of elvitegravir and 150 mg of cobicistat given orally in fixed dose combination once-daily were performed during the second trimester, third trimester, and postpartum...

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...

BACKGROUND: The prodrug tenofovir alafenamide is associated with improved renal and bone safety compared with tenofovir disoproxil fumarate. We aimed to assess safety, pharmacokinetics, and efficacy of this single-tablet, fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-infected, treatment-naive adolescents. METHODS: We did a 48 week, single-arm, open-label trial in treatment-naive adolescents with HIV from ten hospital clinics in South Africa, Thailand, Uganda, and the USA...

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...

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...

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...