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)
Por:
Imaz, A, Tiraboschi, JM, Niubo, 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 and Podzamczer, D
Publicada:
1 oct 2021
Resumen:
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 (C 24h) 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) log 10 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).
Filiaciones:
Imaz, A:
Univ Barcelona, Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Dept Infect Dis,Human Immunodeficiency Virus HIV, Barcelona, Spain
Tiraboschi, JM:
Univ Barcelona, Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Dept Infect Dis,Human Immunodeficiency Virus HIV, Barcelona, Spain
Niubo, J:
Univ Barcelona, Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Dept Microbiol, Barcelona, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain
Cent Univ Catalonia UVic UCC, Univ Vic, Vic, Spain
Cottrell, ML:
Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27515 USA
Domingo, P:
Santa Creu & St Pau Hosp, Dept Infect Dis, Barcelona, Spain
Chivite, I:
St Joan Despf Moises Broggi Hosp, Dept Internal Med, Barcelona, Spain
:
Germans Trias & Pujol Univ Hosp, Lluita Sida Fdn, Barcelona, Spain
Schauer, A:
Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27515 USA
Van Horne, B:
Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27515 USA
Morenilla, S:
Univ Barcelona, Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Dept Infect Dis,Human Immunodeficiency Virus HIV, Barcelona, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Silva-Klug, A:
Univ Barcelona, Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Dept Infect Dis,Human Immunodeficiency Virus HIV, Barcelona, Spain
Scevola, S:
Univ Barcelona, Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Dept Infect Dis,Human Immunodeficiency Virus HIV, Barcelona, Spain
Garcia, B:
Univ Barcelona, Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Dept Infect Dis,Human Immunodeficiency Virus HIV, Barcelona, Spain
Kashuba, ADM:
Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27515 USA
Podzamczer, D:
Univ Barcelona, Bellvitge Univ Hosp, Bellvitge Biomed Res Inst, Dept Infect Dis,Human Immunodeficiency Virus HIV, Barcelona, Spain
Green Published
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