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 (Spanish HIV/AIDS Research Network, PreEC/RIS 58).

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.

Conclusion: 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.