OBJECTIVES: To evaluate dolutegravir and elvitegravir/cobicistat 
pharmacokinetics in HIV-negative volunteers up to 10 days after drug cessation.
METHODS: Healthy volunteers received 50 mg of dolutegravir once-daily for 10 
days, then underwent a 9 day wash-out period, and then received 
elvitegravir/cobicistat as part of Stribild(®) (245 mg of tenofovir, 200 mg of 
emtricitabine, 150 mg of elvitegravir and 150 mg of cobicistat) for 10 days. 
Serial pharmacokinetic (PK) sampling occurred prior to the final dose of each 
course and at regular intervals for up to 216 h (10 days) after drug cessation. 
Concentrations were determined by LC-MS/MS, and PK parameters were illustrated 
as geometric mean and 90% CI.
RESULTS: Seventeen volunteers completed the study. For dolutegravir, plasma 
terminal elimination t1/2 to the last measurable concentration (within 216 h) 
was longer than its t1/2 within the dosing interval (0-24 h): 14.3 h (12.9-15.7 
h) versus 23.1 h (19.7-26.6 h); conversely, the terminal elimination t1/2 for 
elvitegravir was lower than its t1/2 within the dosing interval (0-24 h): 10.8 h 
(9.7-13.0 h) versus 5.2 h (4.7-6.1 h). Dolutegravir concentrations were above 
the protein-adjusted (PA) IC90 (64 ng/mL) in 100% of subjects after 36 and 48 h 
and in 94% after 60 and 72 h. All subjects had detectable dolutegravir 
concentrations at 96 h, a mean of 23.5% above the IC90. Elvitegravir 
concentrations were above the PA IC95 (45 ng/mL) in 100% of subjects at 24 h, 
65% at 36 h but 0% after 48 h.
CONCLUSIONS: Our data show marked differences in the elimination rates of 
dolutegravir and elvitegravir following treatment interruption, which is likely 
to impact the extent to which drug doses can be delayed or missed. They suggest 
that clinical differences may emerge in patients who have suboptimal adherence.