Trial reportThe lancet. HIV2025

Statin effects on the incidence of major non-cardiovascular disease events among a global cohort of people with HIV: a randomised controlled trial.

Marissa R Diggs, Triin Umbleja, Sara McCallum, Markella V Zanni, Sarah M Chu, Kathleen V Fitch, Gerald S Bloomfield, Judith S Currier, Esteban Martinez, Philip E Castle and 14 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in The lancet. HIV, 2025. The graph read 1 number from its abstract, feeding 1 cell of the map: it finds no clear difference in 1. It reports registered trial NCT02344290. Cited by 1 paper.

1number the graph read from it
1cell of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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.

← favours the treatmentfavours the comparator →
1 · no effect
Major non-CVD events (including AIDS-defining events, non-AIDS-defining cancers, renal disease, and liver disease)pitavastatin 4 mg daily vs placebono clear difference · ascvdfeeds one cell of the map
HR 0.920.76 to 1.130.44
Over a median 5.6 years (IQR 4.7-6.3) of follow-up, the incidence of major non-CVD events was 9.17 per 1000 person-years in the pitavastatin group and 9.90 per 1000 person-years in the placebo group (hazard ratio [HR], cause-specific: 0.92, 95% CI 0.76-1.13; p=0.44).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Statins×adverse events & safety

InconclusiveOpen on the map →What to test next →

11 readable studies in this cell: 2 favour the treatment, 8 find no difference, 1 favour the comparator.

Belief with this paper
0.16contested · 1 family supports, 4 contradict · against placebo
Without it
0.20This paper moves it by −0.04.
← favours the treatmentfavours the comparator →
1 · no effect
This paper7,769 enrolled · 2015
HR 0.920.76 to 1.13
NCT03944512102 enrolled · 2019
RR 0.690.11 to 2.95
4 · 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.

NCT02344290 phase3completed

Randomized Trial to Prevent Vascular Events in HIV - REPRIEVE

Ran2015Enrolled7,769Registered outcomes37Posted comparisons40ConditionsCardiovascular Diseases, HIVArmsPitavastatin, Placebo
Open the trial in the graph
5 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
6 · The record

Corrections and comments

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

7 · Who and what money

Authors and funding

24 authors.

Marissa R DiggsMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Triin UmblejaCenter for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA.
Sara McCallumMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Markella V ZanniMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Sarah M ChuMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Kathleen V FitchMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Gerald S BloomfieldDepartment of Medicine, Duke Global Health Institute and Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Judith S CurrierDivision of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Esteban MartinezInfectious Diseases Service, Hospital Clinic and University of Barcelona, Barcelona, Spain; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
Philip E CastleDivisions of Cancer Prevention and Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Aya AwwadMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Mamta K JainDepartment of Medicine, UT Southwestern, Dallas, TX, USA.
Roger BedimoDepartment of Medicine, UT Southwestern, Dallas, TX, USA.
Bronwyn HendricksCentre for TB Research and Innovation, University of Cape Town Lung Institute, Cape Town, South Africa.
Jose NarreaAsociacion Civil Impacta Salud Y Educacion, San Miguel Clinical Research Site, Lima, Peru.
Vincente EstradaDivision of Infectious Diseases, Hospital Clínico San Carlos/IdiSSC, Ciberinfec, Universidad Complutense Madrid, Madrid, Spain.
Jorge PintoDepartment of Pediatrics, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
Judith A AbergDivision of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Carlos D MalvestuttoDivision of Infectious Diseases, Ohio State University Medical Center, Columbus, OH, USA.
Carl J FichtenbaumDivision of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Michael T LuCardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Heather J RibaudoCenter for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA.
Pamela S DouglasDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Steven K GrinspoonMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: sgrinspoon@mgh.harvard.edu.

Funding

AIDS Clinical Trials Group for Research on Therapeutics for HIV and Related InfectionsUM1AI068636 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 to 2025
$229.0M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2021 to 2025
$81.6M
AIDS Clinical Trial Group Laboratory CenterUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 to 2025
$54.5M
Boston HIV CTUUM1AI069412 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · 2021 to 2025
$22.8M
UCLA AIDS Prevention and Treatment Clinical Trials UnitUM1AI069424 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 to 2025
$22.2M
Pitt-Ohio State Clinical Trials UnitUM1AI069494 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 to 2025
$13.1M
UNC Center for AIDS Research Core F BiostatisticsP30AI050410 · UNIV OF NORTH CAROLINA CHAPEL HILL · 2001 to 2025
$10.9M
1/2 REPRIEVE Extension for Trial CompletionUG3HL164285 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · 2023 to 2025
$9.5M
ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · MASSACHUSETTS GENERAL HOSPITAL · 1994 to 2025
$6.0M
2/2 REPRIEVE Extension for Trial CompletionU24HL164284 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · 2023 to 2025
$1.7M
NHLBI NIH HHS U01 HL123336NHLBI NIH HHS U01 HL123339NHLBI NIH HHS U24 HL164284NHLBI NIH HHS UG3 HL164285NIAID NIH HHS P30 AI050410NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069412NIAID NIH HHS UM1 AI069424NIAID NIH HHS UM1 AI069494NIAID NIH HHS UM1 AI106701NIDDK NIH HHS P30 DK040561
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundGiven the pleiotropic effects of statins beyond lipid-lowering, statins might positively impact other, non-cardiovascular diseases (non-CVDs). In this study, we prospectively assessed statin effects on non-CVD events and their incidence among people with HIV globally.

methodsThe Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE; ClinicalTrials.gov, NCT02344290) was a randomised, placebo-controlled trial of pitavastatin for CVD prevention took place from 2015 to 2023 at 145 research sites in 12 countries and is completed. In this analysis of prespecified secondary outcomes of REPRIEVE, we assessed effects of pitavastatin 4 mg daily (vs placebo) on major non-CVD events (including AIDS-defining events, non-AIDS-defining cancers, renal disease, and liver disease) and the Strategic Timing of Antiretroviral Treatment (START) trial outcome (a collective measure of morbidity including CVD among people with HIV) using Cox proportional hazards regression, stratified by sex and CD4 cell count.

findingsAmong the 7769 people with HIV enrolled (3888 in the pitavastatin group and 3881 in the placebo group), 6402 participants completed the study (3201 in each group). Over a median 5·6 years (IQR 4·7-6·3) of follow-up, the incidence of major non-CVD events was 9·17 per 1000 person-years in the pitavastatin group and 9·90 per 1000 person-years in the placebo group (hazard ratio [HR], cause-specific: 0·92, 95% CI 0·76-1·13; p=0·44). The incidence of the START outcome was 15·2 per 1000 person-years in the pitavastatin and 18·3 per 1000 person-years in the placebo group (HR 0·83, 95% CI 0·71-0·97; p=0·016), driven by the effect on CVD. In the placebo group, incidences of the non-AIDS-defining cancer and CVD components of the START Trial outcome were highest (5·83 per 1000 person-years and 5·48 per 1000 person-years) whereas AIDS-defining events were less frequent (3·60 per 1000 person-years), and varied across global regions. With pitavastatin, the incidence of CVD was lower compared with placebo (3·36 per 1000 person-years), however non-AIDS-defining cancers remained high (5·40 per 1000 person-years). Non-AIDS-defining cancers were the leading cause of mortality for both groups.

interpretationAmong a global cohort of people with HIV, treatment with pitavastatin showed no major reduction in non-CVD events, including non-AIDS-defining cancers. These findings outline the limitations of statin therapy for the prevention of non-CVD, highlighting the need for other strategies for such events.

fundingNational Institutes of Health, Kowa Pharmaceuticals America, Gilead Sciences, and ViiV Healthcare.

Indexed as

HIV InfectionsHydroxymethylglutaryl-CoA Reductase InhibitorsQuinolinesAdultCardiovascular DiseasesFemaleHumansIncidenceMaleMiddle AgedNeoplasmsProspective StudiesHydroxymethylglutaryl-CoA Reductase InhibitorspitavastatinQuinolines

Identifiers

PMID40180472
PMCPMC12109758

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

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.