Clinical Trials Registration
TAF, human immunodeficiency virus (HIV) infection
DISEASE, CHRONIC DISEASE
ISRCTN22964075.In a pharmacokinetic substudy of the CHAPAS-4 second-line antiretroviral therapy trial, pharmacokinetic profiles of 104 children showed adequate exposure to tenofovir alafenamide fumarate (TAF) and tenofovir when TAF is dosed according to WHO-recommended weight bands and combined with dolutegravir or ritonavir-boosted protease inhibitors.Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in children from a disease with high morbidity and mortality to a chronic disease. ART including 2 nucleoside/nucleotide reverse trabscriptase inhibitors (NRTI-backbone) and an anchor drug (also referred to as third drug or agent) from a different class is still currently recommended for first- and second-line treatment in most settings. For children, current World Health Organization (WHO) standard-of-care second-line ART options include a backbone of abacavir or zidovudine with lamivudine combined with dolutegravir (DTG), lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r), or darunavir/ritonavir (DRV/r) [In adults, a 10-mg TAF dose combined with the pharmacokinetic booster ritonavir or cobicistat achieves similar exposure compared to 25 mg TAF without a booster [Previous studies on TAF-containing FDCs in children >2 years have reported good viral efficacy with dosing related to both weight and coadministration with ritonavir or cobicistat [There are currently no data to support the use of 120/15 mg FTC/TAF and 200/25 mg FTC/TAF formulations in children, in combination with boosted PIs or in combination with the preferred anchor drug DTG.Here we describe the results of a substudy nested within the CHAPAS-4 (Children with HIV in Africa – Pharmacokinetics and Acceptability of Simple second-line antiretroviral regimens) second-line ART clinical trial, investigating the pharmacokinetics of TAF and TFV when combined with a boosted PI or DTG in children weighing >14 kg.