1. ING116070: A Study of the Pharmacokinetics and Antiviral Activity of Dolutegravir in Cerebrospinal Fluid in HIV-1–Infected, Antiretroviral Therapy–Naive Subjects
- Author
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Letendre, Scott L, Mills, Anthony M, Tashima, Karen T, Thomas, Deborah A, Min, Sherene S, Chen, Shuguang, Song, Ivy H, and Piscitelli, Stephen C
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Sexually Transmitted Infections ,HIV/AIDS ,Neurosciences ,Clinical Research ,Infectious Diseases ,6.1 Pharmaceuticals ,5.1 Pharmaceuticals ,Infection ,Adult ,Anti-HIV Agents ,Cerebrospinal Fluid ,Dideoxynucleosides ,Drug Combinations ,HIV Infections ,HIV-1 ,Heterocyclic Compounds ,3-Ring ,Humans ,Lamivudine ,Male ,Middle Aged ,Oxazines ,Piperazines ,Plasma ,Pyridones ,RNA ,Viral ,Treatment Outcome ,Viral Load ,extended ING116070 study team ,HIV ,cerebrospinal fluid ,dolutegravir ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundDolutegravir (DTG), a once-daily, human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF).MethodsING116070 is an ongoing, single-arm, open-label, multicenter study in antiretroviral therapy-naive, HIV-1-infected adults. Subjects received DTG (50 mg) plus abacavir/lamivudine (600/300 mg) once daily. The CSF and plasma (total and unbound) DTG concentrations were measured at weeks 2 and 16. The HIV-1 RNA levels were measured in CSF at baseline and weeks 2 and 16 and in plasma at baseline and weeks 2, 4, 8, 12, and 16.ResultsThirteen white men enrolled in the study; 2 withdrew prematurely, 1 because of a non-drug-related serious adverse event (pharyngitis) and 1 because of lack of treatment efficacy. The 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 copies/mL, respectively. Nine of 11 subjects (82%) had plasma and CSF HIV-1 RNA levels
- Published
- 2014