ACTG, a global clinical trials network focused on HIV and other
infectious diseases, will present an exploratory analysis from the
REPRIEVE trial demonstrating that former and current use of
abacavir was associated with a higher incidence of major adverse
cardiovascular events at AIDS 2024 in Munich, Germany. The oral
presentation will take place on July 26, 2024, as part of the
session Comorbidities: The Heart of the Matter, from 10:30-11:30 am
CEST at Hall B0b/Channel 5 and virtually.
“This carefully constructed analysis adds to the body of
evidence that abacavir use is associated with a higher risk of
cardiovascular events like heart attacks and strokes,” said ACTG
Chair Judith Currier, M.D., M.Sc., University of California Los
Angeles. “These data align with prior studies that had been
considered somewhat controversial because no exact mechanism was
clearly demonstrated and should be taken into account by clinicians
when they evaluate treatment options for people living with
HIV.”
These are the latest findings from REPRIEVE, the first
large-scale clinical trial to test a primary prevention strategy to
reduce the increased risk of cardiovascular disease among people
living with HIV. It found that participants who took pitavastatin
calcium (a daily statin pill that lowers cholesterol) reduced their
risk of major adverse cardiovascular events by 36 percent compared
with those receiving a placebo over a median duration of five years
of follow up.
The analysis being presented at AIDS 2024 evaluated the role of
prior and current use of select antiretroviral treatments
(including abacavir, tenofovir, thymidine analogs, and protease
inhibitors) on the development of major cardiovascular events.
These antiretrovirals were selected based upon prior association
with cardiovascular risk and kidney impairment (future analyses are
planned to examine the role of other antiretrovirals). Among 7,769
participants, 31.3 percent were born female and 65.2 percent were
not white. The median age was 50, LDL (low-density lipoprotein, a
kind of cholesterol) was 108 mg/dL, CD4 count was 621 cell/mm3, and
88 percent had a viral load under 400 copies/mL. Participants had
been taking HIV treatment for a median of 9.5 years. Researchers
found that current or past use of abacavir increased the risk of
major adverse cardiovascular events by 42 and 50 percent,
respectively, while current or past use of other antiretroviral
treatments caused no such increase.
“This analysis is important as we seek to tease out the various
factors that may help reduce cardiovascular risk in people living
with HIV,” said lead study author Carl Fichtenbaum, M.D.,
University of Cincinnati. “While the association between abacavir
and cardiovascular risk is disappointing, it is not a surprise. It
is, however, reassuring that the other HIV therapies included in
the analysis like tenofovir were not associated with a higher
risk.”
REPRIEVE had a number of unique aspects: study participants had
no known prior history of cardiovascular disease, the global cohort
from 12 countries had low-to-moderate risk for cardiovascular
disease, and all study endpoints were independently vetted by the
national study Thrombolysis in Myocardial Infarction (TIMI).
REPRIEVE began in 2015 as cooperative agreements (HL12339,
HL123336, HL164284, and HL164285) and was a collaborative effort
between the National Institutes of Health’s National Heart, Lung,
and Blood Institute (NHLBI) and the National Institute of Allergy
and Infectious Diseases (NIAID), two of the largest NIH institutes.
It received additional funding from the NIH Office of AIDS
Research, Kowa Pharmaceuticals America, Inc. (providers of
pitavastatin calcium and placebo), Gilead Sciences, Inc., and ViiV
HealthCare.
The trial is led by Steven Grinspoon, M.D. (Chair) and Pamela S.
Douglas, M.D. (Co-chair), who led the Clinical Coordinating Center
and Heather Ribaudo, Ph.D. (Lead Statistician) and Michael Lu,
M.D., M.P.H. (Protocol Chair, Mechanistic Substudy of REPRIEVE),
who led the Data Coordinating Center. To learn more, please visit
www.reprievetrial.org.
In addition to these data from REPRIEVE, ACTG will also make the
following presentations at AIDS 2024:
No Evidence of Pitavastatin Effect on Muscle Density or
Area Among People with HIV (REPRIEVE; Poster Presentation:
Tuesday, July 23rd, 12:00-1:00 pm CEST, Poster Exhibition Hall)
Kristine Erlandson, et al. This analysis from the REPRIEVE
mechanistic substudy found that statins did not reduce muscle
density or area. This two-year study of middle-aged people living
with HIV at low-to-moderate risk of cardiovascular disease,
confirmed through imaging that statins were safe and did not cause
significant muscle damage. This is reassuring to people who want to
use statins to lower their risk of cardiovascular events like heart
attacks and strokes.
Efficacy and Safety of Ensitrelvir in Non-Hospitalized
Adults at Standard or High-Risk of Progression to Severe COVID-19:
the SCORPIO-HR Phase 3, Randomized, Double-Blind Placebo-Controlled
Trial (ACTG 5407; Poster Presentation: Tuesday, July 23rd,
12:00-1:00 pm CEST, Poster Exhibition Hall) Kara Chew, et al. While
the oral protease inhibitor ensitrelvir demonstrated anti-viral
activity, safety, and a trend toward shorter time to symptom
resolution compared to placebo, SCORPIO-HR (ACTG 5407) did not meet
its primary endpoint of time to two or more days sustained
resolution of 15 COVID-19 symptoms in outpatient participants at
standard and higher risk for severe disease.
About ACTG ACTG is the world’s
largest and longest running clinical trials network focused on HIV
and other infectious diseases and the people living with them. It
is funded by NIAID and collaborating NIH Institutes under award
numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. Founded in
1987, ACTG conducts research to improve the management of HIV and
its comorbidities; develop a cure for HIV; and innovate treatments
for tuberculosis, hepatitis B, and emerging infectious diseases. It
comprises thousands of dedicated researchers, staff, and community
members who are pursuing research into novel treatments and cures
for infectious diseases at 65 locations across four continents,
with the ultimate goal of advancing science that meaningfully
impacts the lives of the people we serve.
Disclaimer: This content is solely the responsibility of ACTG
and does not necessarily represent the official views of the
NIH.
Media Contact:Jenna Conley,
ACTGjenna@conleycommunications.net