Tissue Pharmacologic and Virologic Determinants of Duodenal and Rectal Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution in HIV-Infected Patients Initiating Antiretroviral Therapy

J Infect Dis. 2017 Oct 17;216(7):813-818. doi: 10.1093/infdis/jix418.

Abstract

Plasma, duodenal, and rectal tissue antiretroviral therapy (ART) drug concentrations, human immunodeficiency virus (HIV) RNA and HIV DNA copy numbers, and recovery of mucosal immunity were measured before and 9 months after initiation of 3 different ART regimens in 26 subjects. Plasma and tissue HIV RNA correlated at baseline and when 9-month declines were compared, suggesting that these compartments are tightly associated. Antiretroviral tissue:blood penetration ratios were above the 50% inhibitory concentration values in almost 100% of cases. There were no correlations between drug concentrations and HIV DNA/RNA. Importantly, no evidence was found for residual viral replication or deficient tissue drug penetration to account for delayed gastrointestinal-associated lymphoid tissue immune recovery.

Trial registration: ClinicalTrials.gov NCT00870363.

Keywords: ART tissue penetration; HIV persistence; antiretroviral concentration; gastrointestinal-associated lymphoid tissue; immune reconstitution.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use
  • Benzoxazines / administration & dosage
  • Benzoxazines / therapeutic use*
  • Cyclohexanes / administration & dosage
  • Cyclohexanes / therapeutic use*
  • DNA, Viral
  • Duodenum / drug effects
  • Duodenum / metabolism
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Lymphoid Tissue / drug effects*
  • Lymphoid Tissue / metabolism
  • Male
  • Maraviroc
  • RNA, Viral
  • Raltegravir Potassium / administration & dosage
  • Raltegravir Potassium / therapeutic use*
  • Rectum / drug effects
  • Rectum / metabolism
  • Triazoles / administration & dosage
  • Triazoles / therapeutic use*

Substances

  • Anti-HIV Agents
  • Benzoxazines
  • Cyclohexanes
  • DNA, Viral
  • RNA, Viral
  • Triazoles
  • Raltegravir Potassium
  • efavirenz
  • Maraviroc

Associated data

  • ClinicalTrials.gov/NCT00870363