Dynamics of the decay of HIV RNA and distribution of bictegravir in the genital tract and rectum in antiretroviral-naïve HIV-1-infected adults treated with bictegravir/emtricitabine/tenofovir alafenamide

Dynamics of the decay of HIV RNA and distribution of bictegravir in the genital tract and rectum in antiretroviral-naïve HIV-1-infected adults treated with bictegravir/emtricitabine/tenofovir alafenamide

Fecha de publicación online: 31/10/2020 Fecha de publicación en papel: 31 Octubre 2020 Revista: Clinical Infectious Diseases

Abstract:

Background: The pharmacokinetics of bictegravir and its association with decay of HIV-1 RNA in genital fluids and the rectum have not yet been addressed.

Methods: Prospective multicenter study of HIV-1-infected, antiretroviral-naive individuals initiating BIC/FTC/TAF. HIV-1 RNA was measured (LOQ 40 copies/mL) in blood plasma (BP), seminal plasma (SP), rectal fluid (RF), and cervicovaginal fluid (CVF) at baseline, at days 3, 7, 14, and 28, and at weeks 12 and 24. Total and protein-unbound bictegravir concentrations were quantified in BP, SP, CVF and rectal tissue (RT) at 24 hours postdose (C24h) on day 28 and week 12 using a validated LC-MS/MS assay.

Results: The study population comprised 15 males and 8 females. In SP, RF, and CVF, baseline HIV-1 RNA was >40 copies/mL in 12/15, 13/15, and 4/8 individuals, with a median 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. 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 bictegravir 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, representing 2.7%, 2.6%, and 28% of the BP concentration, while 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 bictegravir concentrations in SP, RT, and CVF highly exceeded the EC50 value (1.1 ng/mL).

Keywords: HIV-1; antiretroviral therapy; bictegravir; cervicovaginal fluid; rectal tissue; semen.

Autores: Imaz A, Tiraboschi JM, Niubó J, Martinez-Picado J, Cottrell ML, Domingo P, Chivite I, Negredo E, Schauer A, Van Horne B, Morenilla S, Urrea V, Silva-Klug A, Scevola S, Garcia B, Kashuba ADM, Podzamczer D

Suscríbete a la newsletter

Back to Top
Irsi Caixa

Impulsado por:

Fundación 'La Caixa' Generalitat de Catalunya - Departament de Salut

 

HR Excellence in Research

Miembro de:

Cerca

Con la colaboración de: