ING116070: A Study of the Pharmacokinetics and Antiviral Activity of Dolutegravir in Cerebrospinal Fluid in HIV-1–Infected, Antiretroviral Therapy–Naive Subjects

Median dolutegravir concentrations in cerebrospinal fluid were similar to unbound concentrations in plasma and all subjects exceeded the in vitro 50% inhibitory concentration for wild-type viruses (0.2 ng/mL) by ≥66-fold, suggesting therapeutic concentrations are achieved in cerebrospinal fluid..

• Publication year

  2014

• Venue

  Clinical Infectious Diseases

• Publication date

  2014-06-18

• Fields of study

  Medicine

• Identifiers
  DOI 10.1093/cid/ciu477PMID 24944232PMCID 4166983
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2010influential reference
• Raltegravir Cerebrospinal Fluid Concentrations in HIV-1 Infection

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• Darunavir Concentrations in Cerebrospinal Fluid and Blood in HIV-1–Infected Individuals

  2009cited by this paper
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  2008cited by this paper
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  2006cited by this paper
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  1993cited by this paper
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  1977cited by this paper
• Principles of albumin and IgG analyses in neurological disorders. III. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis.

  1977cited by this paper

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