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

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

Author information

1
University of California, Davis Medical Center, Sacramento.
2
Eshelman School of Pharmacy, University of North Carolina, Chapel Hill.
3
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
4
California National Primate Research Center, Davis.
5
University Hospital La Paz and IdiPAZ.
6
University Hospital Ramón y Cajal and IRYCIS, Madrid, Spain.
7
University of Texas Medical Branch, Galveston.
8
Rush University Medical Center, Chicago, Illinois.

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

PMID:
28968888
PMCID:
PMC6279130
DOI:
10.1093/infdis/jix418
[Indexed for MEDLINE]
Free PMC Article

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