fumarates and dolutegravir

We evaluated the pharmacokinetics of tenofovir alafenamide fumarate (TAF) and tenofovir in a subset of African children enrolled in the CHAPAS-4 trial.. Children aged 3-15 years with human immunodeficiency virus infection failing first-line antiretroviral therapy were randomized to emtricitabine/TAF versus standard-of-care nucleoside reverse transcriptase inhibitor combination, plus dolutegravir, atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. Daily emtricitabine/TAF was dosed according to World Health Organization (WHO)-recommended weight bands: 120/15 mg in children weighing 14 to <25 kg and 200/25 mg in those weighing ≥25 kg. At steady state, 8-9 blood samples were taken to construct pharmacokinetic curves. Geometric mean (GM) area under the concentration-time curve (AUC) and the maximum concentration (Cmax) were calculated for TAF and tenofovir and compared to reference exposures in adults.. Pharmacokinetic results from 104 children taking TAF were analyzed. GM (coefficient of variation [CV%]) TAF AUClast when combined with dolutegravir (n = 18), darunavir/ritonavir (n = 34), or lopinavir/ritonavir (n = 20) were 284.5 (79), 232.0 (61), and 210.2 (98) ng*hour/mL, respectively, and were comparable to adult reference values. When combined with atazanavir/ritonavir (n = 32), TAF AUClast increased to 511.4 (68) ng*hour/mL. For each combination, tenofovir GM (CV%) AUCtau and Cmax remained below reference values in adults taking 25 mg TAF with a boosted protease inhibitors.. In children, TAF combined with boosted PIs or dolutegravir and dosed according to WHO-recommended weight bands provides TAF and tenofovir concentrations previously demonstrated to be well tolerated and effective in adults. These data provide the first evidence for use of these combinations in African children.. ISRCTN22964075.

Topics: Adult; Anti-HIV Agents; Antiviral Agents; Atazanavir Sulfate; Child; Darunavir; Emtricitabine; Fumarates; HIV Infections; Humans; Lopinavir; Protease Inhibitors; Ritonavir; Tenofovir

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF) and dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) are currently available for HIV patients.. This study evaluated modifications in the renal safety profile in a large real-world cohort of patients who had received EVG/c/FTC/TAF or DTG/ABC/3TC.. A retrospective observational study of HIV-infected patients who received EVG/c/FTC/TAF or DTG/ABC/3TC between March 2015 and June 2019 at a reference hospital in north-western Spain was conducted. Epidemiological, clinical, immunovirological data and information regarding antiretroviral therapy were recorded. The statistical differences between treatments were calculated.. A total of 457 patients were evaluated, 266 using EVG/c/FTC/TAF and 191 using DTG/ABC/3TC. Up to week 120, serum creatinine improved in both study groups among experienced patients (EVG/c/FTC/TAF 1.01±0.24 vs 0.91±0.19, p<0.001; DTG/ABC/3TC 1.08±0.24 vs 1.02±0.31, p<0.001), while in naïve patients serum creatinine remained stable compared with baseline. Statistically significant differences were found in serum creatinine when comparing both treatments at week 48 in experienced (0.94±0.21 vs 1.09±0.28, p<0.001) and naïve patients (0.89±0.16 vs 1.06±0.20, p=0.001), and among experienced patients at week 120 (0.91±0.19 vs 1.02±0.31, p=0.015) for the EVG/c/FTC/TAF and DTG/ABC/3TC groups, respectively. During the follow-up, 39 patients in EVG/c/FTC/TAF and 33 in DTG/ABC/3TC (p=0.449) discontinued treatment. The main reason for stopping treatment was adverse events, which were similar in both groups.. During the follow-up, patients experienced changes that were not clinically relevant in both treatment groups. Differences in renal events were not found.

Topics: Anti-HIV Agents; Cobicistat; Creatinine; Emtricitabine; Fumarates; HIV Infections; Humans; Lamivudine

The purpose of this research was to develop and validate a stability-indicating RP-HPLC technique for simultaneous quantification of Emtricitabine (EMT), Tenofovir Alafenamide Fumarate (TEN), and Dolutegravir Sodium (DOL) in bulk and in their combined formulation.. The developed approach was done on Exterra C18 column (150×4.6mm, 5μm) and Methanol and Buffer (comprising 0.1 (v/v) of Triethylamine and o-phosphoric acid in water, pH 2.6) as mobile phase in the proportion of 75:25 (v/v), eluted at 1mL/min. The analytes were quantified using DAD detector at 265nm.. The approach was validated in accordance with the ICH guidelines. Linearity, precision, accuracy, specificity, Limit of Detection (LOD), Limit of Quantitation (LOQ), and robustness were used to validate the proposed method. Linear response was found in the range of 500-1500μg/mL for EMT, 62.5-187.5μg/mL for TEN and 125-375μg/mL for DOL. The LOD values of EMT, TEN and DOL were found 91.78μg/mL, 10.47μg/mL and 19.28μg/mL correspondingly. The LOQ values of EMT, TEN and DOL were found and 278.11μg/mL, 31.74μg/mL and 58.42μg/mL correspondingly. The assay outcomes for all drugs were observed between 99.11-100.84%. To access the method's stability indicating capabilities, the drugs were exposed to various environmental (acid, alkaline, neutral, oxidative, photolytic and thermal) conditions.. The established approach was considered to be accurate, linear, precise, specific, robust and it can be utilized to analyse the drugs mentioned in its tablet.

Topics: Chromatography, High Pressure Liquid; Drug Stability; Emtricitabine; Fumarates