Evidence map›Paper›PMID 32168200›Full record

ArticleJournal of acquired immune deficiency syndromes (1999)2020

Antiretroviral Therapy Concentrations Differ in Gut vs. Lymph Node Tissues and Are Associated With HIV Viral Transcription by a Novel RT-ddPCR Assay.

Sulggi A Lee, Sushama Telwatte, Hiroyu Hatano, Angela D M Kashuba, Mackenzie L Cottrell, Rebecca Hoh, Teri J Liegler, Sophie Stephenson, Ma Somsouk, Peter W Hunt and 3 more

Open access · greenAbstract read
In one paragraph

Article in Journal of acquired immune deficiency syndromes (1999), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

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  17. Pharmacology of HIV Cure: Site of Action.Clinical pharmacology and therapeutics · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Sulggi A LeeDivision of Infectious Diseases, HIV, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA.
Sushama TelwatteDivision of Infectious Diseases, HIV, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA.
Hiroyu HatanoDivision of Infectious Diseases, HIV, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA.
Angela D M KashubaDivision of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Eschelman School of Pharmacy, Raleigh, NC.
Mackenzie L CottrellDivision of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Eschelman School of Pharmacy, Raleigh, NC.
Rebecca HohDivision of Infectious Diseases, HIV, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA.
Teri J LieglerDivision of Infectious Diseases, HIV, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA.
Sophie StephensonDivision of Infectious Diseases, HIV, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA.
Ma SomsoukDivision of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA.
Peter W HuntDivision of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA; and.
Steven G DeeksDivision of Infectious Diseases, HIV, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA.
Steven YuklDivision of Infectious Diseases, HIV, and Global Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA.
Radojka M SavicDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA.
University of California, San Francisco · USSan Francisco VA Medical Center · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Monica Gandhi · 1988 to 2026
$93.6M
Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
Viral reservoirs and sanctuaries in HAART - treated patients: role and mechanismsU19AI096109 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SEKALY, RAFICK PIERRE · 2011 to 2015
$29.5M
Clinical and Transtional Science InstituteKL2TR000143 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$11.9M
Novel single genome approaches to determine the mechanisms of HIV latent infection in blood, gut, and lymph nodesR01DK120387 · NIDDK · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI LICHTERFELD, MATHIAS, YUKL, STEVEN A · 2019 to 2023
$4.1M
Investigating Mechanisms of HIV Persistence in the GutR01DK108349 · NIDDK · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI YUKL, STEVEN A · 2015 to 2019
$2.2M
Understanding HIV latency reversal and clearance of infected cells in vivoR01AI132128 · NIAID · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI WONG, JOSEPH K, YUKL, STEVEN A · 2017 to 2021
$1.9M
Preventing the Establishment of Enfuvirtide-resistance in the Latent ReservoirK24AI069994 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DEEKS, STEVEN GRANT · 2007 to 2016
$1.5M
A pharmacogenomics study of HIV latency: the role of PD-1 signalingK23GM112526 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEE, SULGGI ANGELA · 2014 to 2018
$908k
NCATS NIH HHS KL2 TR000143NIAID NIH HHS K24 AI069994NIAID NIH HHS P30 AI027763NIAID NIH HHS P30 AI050410NIAID NIH HHS R01 AI132128NIAID NIH HHS U19 AI096109NIDDK NIH HHS R01 DK108349NIDDK NIH HHS R01 DK120387NIGMS NIH HHS K23 GM112526
6 · The paper itself

Abstract

backgroundMost HIV-infected cells during antiretroviral therapy (ART) persist in lymphoid tissues. Studies disagree on whether suboptimal tissue ART concentrations contribute to ongoing HIV replication during viral suppression.

methodsWe performed a cross-sectional study in virally-suppressed HIV+ participants measuring lymphoid tissue ART [darunavir (DRV), atazanavir (ATV), and raltegravir (RAL)] concentrations by LC-MS/MS assay. Tissue and plasma ART concentrations were used to estimate TPRs and drug-specific tissue:inhibitory concentration ratios (TICs). HIV DNA and sequentially produced HIV RNA transcripts were quantified from rectal biopsies using droplet digital PCR (ddPCR) assays.

resultsTissue samples were collected in duplicate from 19 participants: 38 rectal, 8 ileal (4 RAL, 2 DRV, 2 ATV), and 6 lymph node (4 RAL, 2 DRV) samples. Overall, median TICs were higher for RAL than DRV or ATV (both P = 0.006). Median TICs were lower in lymph nodes vs. ileum (0.49 vs. 143, P = 0.028) or rectum (33, P = 0.019), and all ART levels were below target concentrations. Higher rectal TICs were associated with lower HIV RNA transcripts (read-through, long LTR, and Nef, P all < 0.026) and a lower long LTR RNA/long LTR DNA ratio (P = 0.021).

conclusionsWe observed higher tissue ART concentrations in ileum and rectum compared with lymph nodes. We observed higher HIV transcription in participants with lower rectal ART concentrations. These findings add to the limited data supporting the idea that viral transcription may be influenced by ART concentrations in lymphoid tissues. Further exploration of tissue pharmacokinetics is needed in future HIV eradication strategies.

Indexed as

AdultAnti-HIV AgentsAntiretroviral Therapy, Highly ActiveAtazanavir SulfateBiopsyCD4-Positive T-LymphocytesCross-Sectional StudiesDarunavirFemaleGastrointestinal TractHIV-1HIV InfectionsHumansIleumLymph NodesMaleAnti-HIV AgentsAtazanavir SulfateDarunavirRaltegravir Potassium

Identifiers

PMID32168200
PMCPMC7286563
OpenAlexW3011923809

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.