Dynamics of the Decay of Human Immunodeficiency Virus (HIV) RNA and Distribution of Bictegravir in the Genital Tract and Rectum in Antiretroviral-naive Adults Living With HIV–1 Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (Spanish HIV/AIDS Research Network, PreEC/RIS 58)
| Autor: | Daniel Podzamczer, Sandra Morenilla, Brian Van Horne, Sofía Scévola, Amanda P. Schauer, Victor Urrea, Pere Domingo, Javier Martinez-Picado, Ana C Silva-Klug, Angela D. M. Kashuba, Eugenia Negredo, Mackenzie L. Cottrell, Benito Garcia, Jordi Niubó, Juan Tiraboschi, Arkaitz Imaz, Ivan Chivite |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Microbiology (medical) Anti-HIV Agents Pyridones 030106 microbiology HIV Infections Emtricitabine Tenofovir alafenamide Piperazines Andrology 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Blood plasma Humans Medicine Genitalia Prospective Studies 030212 general & internal medicine Tenofovir Online Only Articles Alanine Bictegravir business.industry HIV/AIDS research Rectum RNA Amides Infectious Diseases HIV-1 Population study Female business Heterocyclic Compounds 3-Ring medicine.drug |
| Zdroj: | Clin Infect Dis |
| ISSN: | 1537-6591 1058-4838 |
| Popis: | BackgroundThe pharmacokinetics of bictegravir (BIC) and its association with the decay of human immunodeficiency virus (HIV)–1 RNA in genital fluids and the rectum have not yet been addressed.MethodsWe conducted a prospective, multicenter study of antiretroviral-naive people living with HIV-1 and initiating BIC/emtricitabine (FTC)/tenofovir alafenamide (TAF). HIV-1 RNA was measured (limit of quantification, 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline; Days 3, 7, 14, and 28; and Weeks 12 and 24. Total and protein-unbound BIC concentrations at 24 hours postdose (C24h) were quantified in BP, SP, CVF and rectal tissue (RT) on Day 28 and Week 12 using a validated liquid chromatography-tandem mass spectrometry assay.ResultsThe study population comprised 15 males and 8 females. In SP, RF, and CVF, the baseline HIV-1 RNA was >40 copies/mL in 12/15, 13/15, and 4/8 individuals, respectively, with medians of 3.54 (2.41–3.79), 4.19 (2.98–4.70), and 2.56 (1.61–3.56) log10 copies/mL, respectively. The initial decay slope was significantly lower in SP than in RF and BP. The time to undetectable HIV-1 RNA was significantly shorter in SP and RF than in BP. All women achieved undetectable HIV-1 RNA in CVF at Day 14. The median total BIC concentrations in SP, RT, and CVF were 65.5 (20.1–923) ng/mL, 74.1 (6.0–478.5) ng/g, and 61.6 (14.4–1760.2) ng/mL, respectively, representing 2.7%, 2.6%, and 2.8% of the BP concentration, respectively, while the protein-unbound fractions were 51.1%, 44.6%, and 42.6%, respectively.ConclusionsBIC/FTC/TAF led to rapid decay of HIV-1 RNA in genital and rectal fluids. Protein-unbound BIC concentrations in SP, RT, and CVF highly exceeded the half-maximal effective concentration (EC50) value (1.1 ng/mL).Clinical Trials RegistrationEudraCT 2018-002310-12. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|