Evidence map›Paper›PMID 18573931›Full record

ArticleAntimicrobial agents and chemotherapy2008

Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virological effects.

Koen K A Van Rompay, Lucie Durand-Gasselin, Laurie L Brignolo, Adrian S Ray, Kristina Abel, Tomas Cihlar, Abigail Spinner, Christopher Jerome, Joseph Moore, Brian P Kearney and 3 more

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% 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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

  1. Pooled it
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  7. Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2015
    Trial
  8. Trial
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  10. Clinical insights into the association between chronic liver disease and osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
    Review
  11. Article
  12. Article
  13. Article
  14. Nonhuman primate models of pediatric viral diseases.Frontiers in cellular and infection microbiology · 2024
    Review
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  18. Observational
  19. Article
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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.

Koen K A Van RompayCalifornia National Primate Research Center, University of California, Davis, California 95616, USA. kkvanrompay@ucdavis.edu
Lucie Durand-Gasselin
Laurie L Brignolo
Adrian S Ray
Kristina Abel
Tomas Cihlar
Abigail Spinner
Christopher Jerome
Joseph Moore
Brian P Kearney
Marta L Marthas
Hans Reiser
Norbert Bischofberger
Gilead Sciences (United States) · USUniversity of California, Davis · US

Funding

ZONA PELLUCIDA PEPTIDES AS IMMUNOCONTRACEPTIVE ANTIGENSP51RR000169 · NCRR · UNIVERSITY OF CALIFORNIA DAVIS · PI HYDE, DALLAS MELVIN · 1985 to 2011
$126.2M
NCRR NIH HHS P51 RR000169NCRR NIH HHS RR-00169
6 · The paper itself

Abstract

The reverse transcriptase (RT) inhibitor tenofovir (TFV) is highly effective in the simian immunodeficiency virus (SIV) macaque model of human immunodeficiency virus infection. The current report describes extended safety and efficacy data on 32 animals that received prolonged (>or=1- to 13-year) daily subcutaneous TFV regimens. The likelihood of renal toxicity (proximal renal tubular dysfunction [PRTD]) correlated with plasma drug concentrations, which depended on the dosage regimen and age-related changes in drug clearance. Below a threshold area under the concentration-time curve for TFV in plasma of approximately 10 microg x h/ml, an exposure severalfold higher than that observed in humans treated orally with 300 mg TFV disoproxil fumarate (TDF), prolonged TFV administration was not associated with PRTD based on urinalysis, serum chemistry analyses, bone mineral density, and clinical observations. At low-dose maintenance regimens, plasma TFV concentrations and intracellular TFV diphosphate concentrations were similar to or slightly higher than those observed in TDF-treated humans. No new toxicities were identified. The available evidence does not suggest teratogenic effects of prolonged low-dose TFV treatment; by the age of 10 years, one macaque, on TFV treatment since birth, had produced three offspring that were healthy by all criteria up to the age of 5 years. Despite the presence of viral variants with a lysine-to-arginine substitution at codon 65 (K65R) of RT in all 28 SIV-infected animals, 6 animals suppressed viremia to undetectable levels for as long as 12 years of TFV monotherapy. In conclusion, these findings illustrate the safety and sustained benefits of prolonged TFV-containing regimens throughout development from infancy to adulthood, including pregnancy.

Indexed as

Anti-HIV AgentsDisease Models, AnimalPregnancy Complications, InfectiousReverse Transcriptase InhibitorsSimian Acquired Immunodeficiency SyndromeAdenineAge FactorsAnimalsFemaleHIV-1HIV InfectionsHumansMacaca mulattaOrganophosphonatesPregnancySimian Immunodeficiency VirusAdenineAnti-HIV AgentsOrganophosphonatesReverse Transcriptase InhibitorsTenofovir

Identifiers

PMID18573931
PMCPMC2533487
OpenAlexW1963603865

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.