Publication Abstract Display
Type: Published Manuscript
Title: ING116070: A study of the pharmacokinetics and antiviral activity of Dolutegravir in cerebrospinal fluid in HIV-1-infected, ART-naive subjects.
Authors: Letendre SL, Mills AM, Tashima KT, Thomas DA, Min SS, Chen S, Song IH, Piscitelli SC
Year: 2014
Publication: Clinical Infectious Diseases : An Official Publication of The Infectious Diseases Society of America
Volume: 59 Issue: 7 Pages: 1032-1037
Abstract: Dolutegravir (DTG), a once-daily, HIV-1 integrase inhibitor, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF). METHODS:  ING116070 is an ongoing, single-arm, open-label, multicenter study in antiretroviral therapy-naive, HIV-1-infected adults. Subjects received DTG 50 mg+abacavir/lamivudine 600/300 mg once daily. CSF and plasma (total and unbound) DTG concentrations were measured at Weeks 2 and 16. HIV-1 RNA was measured in CSF at Baseline and Weeks 2 and 16 and in plasma at Baseline and Weeks 2, 4, 8, 12 and 16. RESULTS:  Thirteen white males enrolled; 2 withdrew prematurely, 1 for a non-drug-related serious adverse event (pharyngitis) and 1 for lack of efficacy. Median DTG concentrations in CSF were 18 ng/mL (range, 4-23 ng/mL) at Week 2 and 13 ng/mL (4-18 ng/mL) at Week 16. Ratios of DTG CSF to total plasma concentration were similar to the unbound fraction of DTG in plasma. Median changes from Baseline in CSF (n=11) and plasma (n=12) HIV-1 RNA were -3.42 and -3.04 log10 c/mL, respectively. Nine of 11 subjects (82%) had plasma and CSF HIV-1 RNA below 50 c/mL and 10/11 subjects (91%) had CSF HIV-1 RNA below 2 c/mL at Week 16. CONCLUSIONS:  DTG concentrations in CSF were similar to unbound plasma concentrations and exceeded the in vitro 50% inhibitory concentration for wild-type HIV (0.2 ng/mL), suggesting DTG achieves therapeutic concentrations in the CNS. HIV-1 RNA reductions were similar in CSF and plasma.

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