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). (31st October 2020)

• Record Type: Journal Article
• Authors: Imaz, Arkaitz; Tiraboschi, Juan M; Niubó, Jordi; Martinez-Picado, Javier; Cottrell, Mackenzie L; Domingo, Pere; Chivite, Ivan; Negredo, Eugenia; Schauer, Amanda; Van Horne, Brian; Morenilla, Sandra; Urrea, Víctor; Silva-Klug, Ana; Scévola, Sofía; Garcia, Benito; Kashuba, Angela D M; Podzamczer, Daniel
• Is Part Of: Clinical infectious diseases. Volume 73:Number 7(2021)
• Page Start: e1991
• Page End: e1999
• Publication Date: 2020-10-31
• Subjects: HIV-1 -- antiretroviral therapy -- bictegravir -- genital fluids -- rectum; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa1416
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: The 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. Methods: We 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. Results: The 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. Conclusions: BIC/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 Registration: EudraCT 2018-002310-12. Abstract : Antiretroviral-naive adults living with human immunodeficiency virus (HIV) who initiated antiretroviral therapy with bictegravir/emtricitabine/tenofovir alafenamide had rapid HIV-1 RNA suppression in genital and rectal fluids. Protein-unbound bictegravir concentrations highly exceeded the half-maximal effective concentration value in genital and rectal fluids.