Evidence map›Paper›PMID 25433664›Full record

Trial reportHIV clinical trials

Renal and metabolic toxicities following initiation of HIV-1 treatment regimen in a diverse, multinational setting: a focused safety analysis of ACTG PEARLS (A5175).

F Touzard Romo, L M Smeaton, T B Campbell, C Riviere, R Mngqibisa, M Nyirenda, K Supparatpinyo, N Kumarasamy, J G Hakim, T P Flanigan

Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in HIV clinical trials. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 34% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Clinical Considerations in the Selection of Preexposure Prophylaxis for HIV Prevention in Canada.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022
    Review
  5. Article
  6. Article
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

10 authors at 9 institutions in 7 countries.

F Touzard RomoThe Miriam Hospital, Providence, Rhode Island, USA Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
L M SmeatonHarvard School of Public Health, Boston, Massachusetts, USA.
T B CampbellUniversity of Colorado Denver, Aurora, Colorado, USA.
C RiviereInstitut Nacional de Laboratoire et Recherches, Port-au-Prince, Haiti.
R MngqibisaUniversity of KwaZulu-Natal, Durban, South Africa.
M NyirendaCollege of Medicine - Johns Hopkins Research Project, Blantyre, Malawi.
K SupparatpinyoChiang Mai University, Chiang Mai, Thailand.
N KumarasamyYRG Centre for AIDS Research and Education, Chennai, India.
J G HakimUniversity of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
T P FlaniganThe Miriam Hospital, Providence, Rhode Island, USA Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Miriam Hospital · USChiang Mai University · THHarvard University · USUniversity of Colorado Denver · USUniversity of Haiti · HTUniversity of KwaZulu-Natal · ZAUniversity of Malawi · MWUniversity of Zimbabwe · ZWYR Gaitonde Centre for AIDS Research and Education · IN

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
AIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010
$147.1M
Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6M
Virology, Immunology, and Microbiology CoreP30AI050410 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2001 to 2026
$76.9M
UZ-UCSF CTUUM1AI069436 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZVAVAHERA MIKE CHIRENJE, LYNDA STRANIX-CHIBANDA · 2012 to 2026
$75.9M
Statistical and Data Management Center for the AIDS Clinical Trials GroupU01AI068634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HUGHES, MICHAEL DAVID · 2006 to 2010
$71.9M
University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit 2024 SupplementUM1AI069423 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, MINA CHRISTINE HOSSEINIPOUR · 2012 to 2026
$71.8M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024156 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$53.0M
UCLA AIDS Prevention and Treatment Clinical Trials UnitUM1AI069424 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Judith S. Currier, RAPHAEL J LANDOVITZ · 2012 to 2026
$51.8M
Translational ScienceP30AI042853 · NIAID · MIRIAM HOSPITAL · PI LARRY K BROWN · 1998 to 2026
$51.7M
UCSD Department of Medicine HIV/AIDS Clinical Trials UnitUM1AI069432 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TIMOTHY J. WILKIN · 2012 to 2026
$50.4M
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6 · The paper itself

Abstract

backgroundConvenient dosing, potency, and low toxicity support use of tenofovir disoproxil fumarate (TDF) as preferred nucleotide reverse transcriptase inhibitor (NRTI) for HIV-1 treatment. However, renal and metabolic safety of TDF compared to other NRTIs has not been well described in resource-limited settings.

methodsThis was a secondary analysis examining the occurrence of renal abnormalities (RAs) and renal and metabolic serious non-AIDS-defining events (SNADEs) through study follow-up between participants randomized to zidovudine (ZDV)/lamivudine/ efavirenz and TDF/emtricitabine/efavirenz treatment arms within A5175/PEARLS trial. Exact logistic regression explored associations between baseline covariates and RAs. Response profile longitudinal analysis compared creatinine clearance (CrCl) over time between NRTI groups.

resultsTwenty-one of 1,045 participants developed RAs through 192 weeks follow-up; there were 15 out of 21 in the TDF arm (P = .08). Age 41 years or older (odds ratio [OR], 3.35; 95% CI, 1.1-13.1), his- tory of diabetes (OR, 10.7; 95% CI, 2.1-55), and lower baseline CrCl (OR, 3.1 per 25 mL/min decline; 95% CI, 1.7-5.8) were associated with development of RAs. Renal SNADEs occurred in 42 participants; 33 were urinary tract infections and 4 were renal failure/insufficiency; one event was attributed to TDF. Significantly lower CrCl values were maintained among patients receiving TDF compared to ZDV (repeated measures analysis, P = .05), however worsening CrCl from baseline was not observed with TDF exposure over time. Metabolic SNADEs were rare, but were higher in the ZDV arm (20 vs 3; P < .001).

conclusionsTDF is associated with lower serious metabolic toxicities but not higher risk of RAs, serious renal events, or worsening CrCl over time compared to ZDV in this randomized multinational study.

Indexed as

HIV-1AdultAnti-HIV AgentsDrug Therapy, CombinationFemaleHIV InfectionsHumansKidney DiseasesLogistic ModelsMaleMetabolic DiseasesMiddle AgedAnti-HIV Agentsantiretroviralsmetabolic toxicityrenal toxicitytenofovirzidovudine

Identifiers

PMID25433664
PMCPMC4357257
OpenAlexW2038629512

What OpenQuestion holds

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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.