Trial reportThe lancet. HIV2026

Pitavastatin effects on lipids in relation to major adverse cardiovascular events: a REPRIEVE secondary analysis.

Triin Umbleja, Mohammad U Zafar, Sara McCallum, Arijeet K Gattu, Markella V Zanni, Gerald S Bloomfield, Carlos D Malvestutto, Carl J Fichtenbaum, Judith S Currier, Craig A Sponseller and 13 more

Abstract readRandomized Controlled TrialClinical Trial, Phase III
In one paragraph

Trial report in The lancet. HIV, 2026. The graph read 1 number from its abstract, feeding 1 cell of the map: it supports the treatment in 1. Not yet cited in PubMed.

1number the graph read from it
1cell of the map it votes in
0citing 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 →
0.51 · no effect
Lipidsfavours the treatment · against placebo · ascvd, dyslipidemiafeeds one cell of the map
RR 0.320.30 to 0.34
The estimated risk of LDL of ≥100 mg/dL at month 12 was 0.18 in the pitavastatin group and 0.57 in the placebo group (relative risk 0.32, 95% CI 0.30-0.34).

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×lipids

SupportsOpen on the map →What to test next →

38 readable studies in this cell: 27 favour the treatment, 5 find no difference, 6 favour the comparator.

Belief with this paper
0.50contested · 21 families support, 7 contradict · against placebo
Without it
0.50This paper does not move the number.
← favours the treatmentfavours the comparator →
1 · no effect
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.

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

5 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

23 authors.

Triin UmblejaCenter for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA.
Mohammad U ZafarAtherothrombosis Research Unit, Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Sara McCallumMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Arijeet K GattuMetabolism 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.
Gerald S BloomfieldDepartment of Medicine, Duke Global Health Institute, and Duke Clinical Research Institute, Duke University, Durham, NC, 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.
Judith S CurrierDivision of Infectious Diseases, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Craig A SponsellerKowa Pharmaceuticals America, Montgomery, AL, USA.
Marissa R DiggsMetabolism 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.
Alex B LuCenter for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA.
Marshall J GlesbyDivision of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Jack T StapletonDepartment of Medicine, The University of Iowa and The Iowa City Veterans Affairs Health Care System, Iowa City, IA, USA.
Michael FrankDivision of Infectious Diseases, Medical College of Wisconsin, Milwaukee, WI, USA.
Kim-Lien NguyenDivision of Cardiology, David Geffen School of Medicine at UCLA and VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
Rachel A Bender IgnacioDivision of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA.
Win Min HanHIV-NAT, Thai Red Cross AIDS and Infectious Diseases Research Centre, Bangkok, Thailand; The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.
Pamela S DouglasDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Judith A AbergDivision of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Heather J RibaudoCenter for Biostatistics in AIDS Research, Harvard T H Chan School of Public Health, Boston, MA, USA.
Steven K GrinspoonMetabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: sgrinspoon@mgh.harvard.edu.

Funding

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
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 UM1 AI068634NIDDK NIH HHS P30 DK040561
8 · The paper itself

Abstract

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

backgroundThe Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) found a 36% reduction in major adverse cardiovascular events (MACE) with pitavastatin in people with HIV. Little is known about the relationship between lipid lowering and MACE in this population. We evaluated pitavastatin effects on lipids and examined mediation of pitavastatin effects on MACE through lipid lowering.

methodsREPRIEVE was a randomised, double-blind, placebo-controlled phase 3 trial evaluating pitavastatin (4 mg daily) or placebo for prevention of MACE in people with HIV. Participants aged 40-75 years, on stable combination antiretroviral therapy (ART), and at low-to-moderate atherosclerotic cardiovascular disease risk with minimally elevated LDL were followed up for a median of 5·6 years. Centrally tested fasting lipids were captured at entry and annually thereafter. The primary MACE outcome, reported previously, was time to first MACE. Here, we report secondary outcomes on fasting lipids. Linear mixed-effects models were used for assessment of the pitavastatin effect on lipids, Cox regression for relationship of lipids to MACE, and Vansteelandt method for mediation analysis.

findingsREPRIEVE enrolled 7769 participants from March 26, 2015, to July 31, 2019, in 12 countries across five Global Burden of Diseases super-regions. The median baseline LDL was 108 mg/dL, and similar across treatment groups. Pitavastatin effects were primarily observed on LDL, with a modest reduction in triglycerides and no apparent effect on HDL. Based on the longitudinal data modelling, the estimated treatment group difference in LDL at month 12 (pitavastatin minus placebo) was -30 mg/dL (95% CI -31 to -29), corresponding to a 30% reduction. The estimated risk of LDL of ≥100 mg/dL at month 12 was 0·18 in the pitavastatin group and 0·57 in the placebo group (relative risk 0·32, 95% CI 0·30-0·34). A 30% lower time-updated average LDL was associated with 20% lower risk of primary MACE (hazard ratio 0·80, 95% CI 0·68-0·94). Of the pitavastatin effect on MACE, 68% was estimated to be mediated through LDL, although with low precision (95% CI 15-574).

interpretationLDL is strongly related to MACE, and LDL lowering should be an important goal of primary cardiovascular prevention in people with HIV, even in those with minimally elevated LDL. Treatment should aim to achieve accepted primary care prevention targets for LDL.

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

Indexed as

Cardiovascular DiseasesHIV InfectionsHydroxymethylglutaryl-CoA Reductase InhibitorsLipidsQuinolinesAdultAgedCholesterol, LDLDouble-Blind MethodFemaleHumansMaleMiddle AgedCholesterol, LDLHydroxymethylglutaryl-CoA Reductase InhibitorsLipidspitavastatinQuinolines

Identifiers

PMID41936375
PMCPMC13122762

What Socratic holds

Texttitle and abstract
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.