Darunavir in childrens

In this multicenter pharmacokinetic study in HIV-infected children (6-12 years), we validated the approved once-daily darunavir/ritonavir dosing recommendations.The geometric mean darunavir area under the plasma concentration-time curve was 63.1 h.mg/l, substantially lower than the mean value observed in adults. However, all trough levels were adequate and short-term virological outcome was good. These data support the use of the darunavir/ritonavir once-daily dosing recommendations.

BACKGROUND: There is an increasing need for third-line treatment regimens in HIV-infected children with antiretroviral treatment (ART) failure. Data are limited on darunavir/ritonavir (DRV/r)-, raltegravir (RAL)- and etravirine (ETR)-containing regimens in treatment-experienced children from resource-constrained settings receiving these drugs as part of routine care. OBJECTIVE: To describe the characteristics and early outcomes of treatment-experienced children (<20 years of age) in the Western Cape Province of South Africa treated with DRV/r-, RAL- or ETR-containing regimens...

OBJECTIVES: Dyslipidaemia is common in perinatally HIV-infected (PHIV) youth receiving protease inhibitors (PIs). Few studies have evaluated longitudinal lipid changes in PHIV youth after switch to newer PIs. METHODS: We compared longitudinal changes in fasting lipids [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and TC:HDL-C ratio] in PHIV youth enrolled in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP) study who switched to atazanavir/ritonavir (ATV/r)- or darunavir/ritonavir (DRV/r)-based antiretroviral therapy (ART) from an older PI-based ART and those remaining on an older PI...

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...

PURPOSE: Refractory pediatric leukemia remains one of the leading causes of death in children. Intensification of current chemotherapy regimens to improve the outcome in these children is often limited by the effects of drug resistance and cumulative toxicity. Hence, the search for newer agents and novel therapeutic approaches are urgently needed to formulate the next-generation early-phase clinical trials for these patients. MATERIALS AND METHODS: A comprehensive library of antimicrobials, including eight HIV protease inhibitors (nelfinavir [NFV], saquinavir, indinavir, ritonavir, amprenavir, atazanavir, lopinavir, and darunavir), was tested against a panel of pediatric leukemia cells by in vitro growth inhibition studies...

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...

BACKGROUND: The World Health Organization identified a need for evidence to inform revision of second- and third-line antiretroviral therapy (ART) options in children failing ART. We performed an in-depth scoping review of all available literature on second-line and subsequent ART regimens in children younger than 18 years. METHODS: We comprehensively searched, without language or date limitations, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials...

BACKGROUND: The most-used protease-inhibitor in children is Lopinavir-ritonavir (LPV/r), which provides durable suppression of viral load and increases CD4+T-counts. This study describes the virological outcome of the HIV-1-infected paediatric population exposed to LPV/r during 15 years in Spain. METHODOLOGY: Patients from the Madrid Cohort of HIV-1-infected-children and adolescents exposed to LPV/r as different line therapy during 2000-2014 were selected. The baseline epidemiological-clinical features, viral suppression, changes in CD4+T-CD8+T cell counts and drug susceptibility were recorded before and during LPV/r exposure...

BACKGROUND: The World Health Organization (WHO) identified a need for evidence to inform revision of second and third-line antiretroviral therapy (ART) options in children failing ART. We performed an in-depth scoping review of all available literature on second and subsequent line ART regimens in children younger than 18 years. METHODS: We comprehensively searched, without language or date limitations, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the WHO International Clinical Trials Registry Platform and ClinicalTrials...

BACKGROUND: Limited data are available for once-daily (QD) darunavir (DRV)/ritonavir (r) in the pediatric population. Coadministration of etravirine (ETR) may alter the pharmacokinetics (PK) of DRV. We evaluated the PK interactions between DRV/r (QD) and ETR QD or twice-daily (BID) in children, adolescents, and young adults. METHODS: Human immunodeficiency virus-infected subjects 9 to < 24 years old on optimized background therapy including DRV/r 800/100 mg QD alone or combined with ETR 200 mg BID or ETR 400 mg QD were enrolled...

BACKGROUND: Genotyping tests were developed to attenuate the impact of viral resistance. Information about the efficacy in genotype base antiretroviral therapy in children is rare and even more in low- and middle-income countries. METHODS: Sixteen children with antiretroviral therapy (ART) failure and triple-class drug-resistant viruses were included in this study. Protease and retrotranscriptase genotypes were available for all patients. Switch of ART regimen was guided by genotyping data...

BACKGROUND: Surveillance for mid- and long-term antiretroviral therapy (ART) toxicity in children is important for informing treatment guidelines. We assessed the safety of darunavir (DRV) and atazanavir (ATV), commonly used as second-line protease inhibitors following lopinavir/ritonavir, in Europe and Thailand. METHODS: Cohorts contributed individual patient data on adverse events (AE) in those aged <18 years taking DRV and ATV, respectively, to 02/2014. Rates of Division of AIDS (DAIDS) grade ≥3 laboratory AEs were calculated...

Darunavir (Prezista®), administered in combination with ritonavir and background antiretroviral therapy, is approved in the USA and the EU for the treatment of HIV-1 infection in pediatric patients aged ≥3 years. Ritonavir-boosted darunavir provided effective virologic suppression in treatment-naïve adolescents with HIV-1 infection, according to the results of the noncomparative, phase II DIONE trial. Ritonavir-boosted darunavir also had sustained efficacy in treatment-experienced children and/or adolescents with HIV-1 infection, according to the results of the noncomparative, phase II DELPHI and ARIEL trials...

An existing population pharmacokinetic model of darunavir in adults was updated using pediatric data from two studies evaluating weight-based, once-daily dosing of darunavir/ritonavir (ARIEL, NCT00919854 and DIONE, NCT00915655). The model was then used to provide once-daily dosing recommendations for darunavir/ritonavir in pediatric patients aged ≥3 to <12 years. The final model comprised two compartments with first-order absorption and apparent clearance dependent on the concentration of α1-acid glycoprotein...

Treatment-emergent mutations and drug resistance were analyzed in virus from HIV-infected children meeting virologic failure (VF) criteria over 48 weeks following treatment with unboosted fosamprenavir or fosamprenavir/ritonavir-containing regimens in studies APV20002 and APV29005. Both antiretroviral therapy (ART)-naïve and ART-experienced patients were enrolled. Patients met VF criteria by either failing to suppress HIV-RNA to <400 copies/mL through week 24 or after confirmed viral rebound (≥400 copies/mL) anytime through week 48...

OBJECTIVE: To report the outcomes, clinical management decisions and results of resistance testing among a group of children who developed virologic failure on first-line lopinavir/ritonavir (LPV/r)-based therapy from a large cohort of antiretroviral therapy-treated children in Soweto. DESIGN: Historical cohort study. METHODS: Children with virologic failure were identified from a group of 1692 children <3 years who had initiated first-line LPV/r-containing therapy since 2000 up to the end November 2011...

BACKGROUND: ARIEL (Darunavir in treatment-experienced pediatric population) was a phase II, open-label study assessing safety and antiviral activity of darunavir/ritonavir twice daily with an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected pediatric patients (3 to <6 years, weighing 10 to <20 kg). METHODS: The study consisted of an initial 4-week screening period, 48 weeks of treatment and a 4-week follow-up period. Patients initially received darunavir/ritonavir 20/3 mg/kg twice-daily for 2 weeks...

Drug resistance mutations compromise the success of antiretroviral treatment in human immunodeficiency virus type 1 (HIV-1)-infected children. We report the virologic and clinical follow-up of the Madrid cohort of perinatally HIV-infected children and adolescents after the selection of triple-class drug-resistant mutations (TC-DRM). We identified patients from the cohort carrying HIV-1 variants with TC-DRM to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors according to IAS-USA-2013...

BACKGROUND: Twice-daily darunavir/ritonavir is indicated in treatment-experienced children (≥3 years). This study assessed once-daily administration in treatment-naïve adolescents. METHODS: Phase 2, 48-week, open-label, single-arm study evaluating pharmacokinetics, safety and efficacy of once-daily darunavir/ritonavir 800/100 mg in treatment-naïve, HIV-1-infected adolescents (≥12 to <18 years, ≥40 kg) with zidovudine/lamivudine or abacavir/lamivudine...

OBJECTIVES: To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum. PATIENTS AND METHODS: This was a non-randomized, open-label, multicentre, Phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. HIV-infected pregnant women treated with darunavir (800/100 mg once daily or 600/100 mg twice daily) as part of their combination ART were included. Pharmacokinetic curves were recorded in the third trimester and post-partum...