CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

783

Residual HIV Viremia Doubles Cardiovascular Disease Incidence Independent of Classic Risk Factors Twan Otten 1 , Marc Blaauw 2 , Wilhelm A. Vos 3 , Albert L. Groenendijk 4 , Louise E. van Eekeren 1 , Olivier Richel 1 , Mihai Netea 1 , Jan van Lunzen 1 , Niels P. Riksen 1 , Linos Vandekerckhove 5 , Andre J. van der Ven 1 , for the 2000 HIV Human Functional Genomics Partnership Program 1 Radboud University Medical Center, Nijmegen, Netherlands, 2 Elisabeth-TweeSteden Ziekenhuis, Tilburg, Netherlands, 3 OLVG, Amsterdam, Netherlands, 4 Erasmus University Medical Center, Rotterdam, Netherlands, 5 Ghent University, Ghent, Belgium Background: People living with HIV (PLHIV) have a heightened risk of atherosclerotic cardiovascular diseases (CVD) beyond that explained by traditional risk factors, potentially driven by HIV-related inflammation or other HIV-related factors. Although antiretroviral therapy (ART) should result in undetectable plasma viral loads (VL), some PLHIV show unquantifiable low yet detectable VL via PCR testing (Residual viremia, RV). We now propose a role of RV for CVD development. Methods: The 2000HIV study enrolled 1895 virally suppressed PLHIV (2019-2021), divided in a discovery and validation cohort. VL was measured by commercial PCR assays (Roche, Abbott, Hologic or Cepheid). Only PLHIV with VL <40 c/ml (n=1815) were analyzed: compared were PLHIV with RV (unquantifiable low, yet detectable VL) with those with undetectable PCR result. Baseline blood samples were used for proteomics by Olink® Explore panel (~3000 proteins) and functional immunological testing by exposing PBMCs to various stimuli and cytokine level measurements in the supernatant. Incident CVD (stroke, transient ischemic attacks, myocardial infarction, angina pectoris or peripheral artery disease) was registered after two years follow up. Odds ratio (OR) and p value were calculated using multivariate logistic regression accounting for age, sex, smoking, BMI, diabetes, hypertension, hypercholesterolemia and CVD family history. Results: At baseline, 665 PLHIV had RV, 1150 had undetectable VL. Participants with RV had higher VL zenith, and shorter ART duration but did not differ in terms of statin or abacavir use, ART adherence and dual DTG based versus three drug ART nor presence of carotid plaque on ultrasound. Participants with RV more often had a history of myocardial infarction (5.6% vs 2.7% OR 2.28 p=0.01; 7.1% vs 1.5% OR 9.6 p=0.04 in discovery and validation cohort respectively). Notably RV participants were twice as likely to develop a first cardiovascular event during follow up (3.4% vs 1.4% OR 2.58 p=0.01). Comparing PLHIV with and without RV, no differences were observed in the functional immunological assays, however plasma levels of TNF Superfamily member 10, Granzymes (A, B and H) were higher in participants with RV. Conclusion: Our data are the first to suggest that residual viremia is a risk factor for past and future cardiovascular diseases independent from traditional CVD risk factors. The mechanism may be through upregulation of specific inflammatory biomarkers that have also been identified for CVD in non-HIV populations. Temporal Trends of Cardiovascular Disease Incidence in People With HIV From 2001-2021 Background: With an increased focus on cardiovascular disease (CVD) as a leading cause of death in people with HIV, monitoring patterns in CVD incidence and its influencing factors in real-life settings is crucial for informed clinical decision-making. Methods: We followed participants from the D:A:D and RESPOND cohort collaborations from baseline (D:A:D: latest of study entry or 1 Jan 2001; RESPOND: latest of local cohort enrolment or 1 Jan 2012) until the earliest of first CVD event (myocardial infarction [MI], stroke, invasive cardiovascular procedure [ICP]), final follow-up, or 1 Feb 2016 (D:A:D)/31 Dec 2021 (RESPOND). We calculated age-standardised CVD incidence rates (IRs) two-yearly from 2001–2021 and assessed temporal trends by Poisson regression, adjusting for time-updated potential confounders and cohort. Results: Of 66,680 included individuals, 18% were age >50 (median 40, interquartile range [IQR] 33–47) at baseline, 74% were male, 38% current smokers, 45% had dyslipidemia, 8% hypertension, 3% diabetes, and 1% prior CVD. Median CD4 cell count was 437 (270–630). Over a median of 8.8 (4.5–13.1) years (586,510 person-years, PY), there were 2,811 CVD events (IR 4.79/1000 PY [95% confidence interval (CI) 4.62–4.97]; 1363 MIs, 768 strokes, 680 ICPs). While the crude CVD incidence remained relatively stable over time, age-standardised Nadine Jaschinski , for the RESPOND and D:A:D Study Groups Centre of Excellence for Health, Immunity, and Infections, Copenhagen, Denmark

Results: Among 7,769 participants, 31.1% were natal female and 65.2% non-White. Median age was 50 years, LDL 108 mg/dL, 10-year ASCVD risk score 4.5%, diabetes prevalence <1%, and CD4 621 cell/mm 3 . In unadjusted models, RF associated with a higher (P<0.05) risk of first MACE were: older age, male sex, residence in a high-income region, Black/African American race (within high-income regions), family history of premature CVD, current/former smoking, hypertension (HTN), BMI ≥30 kg/m 2 , fasting glucose ≥100 mg/dL, lower HDL, eGFR <90 mL/min/1.73 mm 2 , lower nadir CD4, and detectable HIV-1 RNA (VL). After full adjustment, effects of natal sex, BMI, glucose, eGFR, and nadir CD4 were no longer apparent (P>0.25). Risk for first MACE was higher for older individuals (50-59 and ≥60 vs. 40-49, HR's: 1.98 and 2.11), as well as those with a family history of premature CVD (HR: 1.57), Black/African American race (vs. white race, within high-income regions HR: 1.75), current/former smoking (HR: 1.66), HTN (HR: 1.68), and detectable VL (HR 1.46), and lower for those with higher HDL-C (HR: 0.83). Individuals from a high-income region had a higher risk of first MACE vs. those from other regions, save for those from South Asia. Conclusion: Among a global primary prevention cohort of PWH, factors associated with first MACE after accounting for statin effect included modifiable RF of cigarette smoking, HTN, and detectable VL. A protective effect of female sex was not apparent. Additional work is needed to understand the higher risk of MACE associated with residence in a high-income region, particularly among Black/African American PWH. The figure, table, or graphic for this abstract has been removed. Performance of the ACC/AHA Pooled Cohort Equations for Risk Prediction in the Global REPRIEVE Trial Steven K Grinspoon 1 , Heather J. Ribaudo 2 , Virginia Triant 1 , Kathleen V. Fitch 1 , Amy Kantor 2 , Judith S. Currier 3 , Gerald S. Bloomfield 4 , Marissa Diggs 1 , Judith A. Aberg 5 , Carlos D. Malvestutto 6 , Carl J. Fichtenbaum 7 , Michael T. Lu 1 , Markella V. Zanni 1 , Pamela S. Douglas 4 , for the REPRIEVE Investigators 1 Massachusetts General Hospital, Boston, MA, USA, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 University of California Los Angeles, Los Angeles, CA, USA, 4 Duke University School of Medicine, Durham, NC, USA, 5 Icahn School of Medicine at Mt Sinai, New York, NY, USA, 6 The Ohio State University, Columbus, OH, USA, 7 University of Cincinnati, Cincinnati, OH, USA Background: People with HIV (PWH) have a higher burden of cardiovascular (CV) disease than the general population; estimating this risk is an essential component of prevention. However, it is unknown how well the 2013 ACC/AHA guideline-recommended Pooled Cohort Equation (PCE) estimates risk among PWH globally. Leveraging the international REPRIEVE Trial, which prospectively adjudicated incident CV events, we compared observed vs. predicted event rates in PWH not taking statins. Methods: The REPRIEVE Trial used the PCE to determine eligibility of PWH at low-moderate CV risk for a statin primary prevention trial. We now assess discrimination and calibration of the PCE in those randomized to placebo (n=3869) as well as those randomized to statin but never starting treatment (n=24). To align with the median 5-year follow up in REPRIEVE, a 5-year risk score was recalculated for this analysis per established method, and follow-up beyond 5 years was censored. We limited outcomes to the specific CV events predicted by the PCE (hard MACE): CV death, myocardial infarction (MI), and stroke. We calculated the C-statistic, the observed: expected (O:E) event ratio and the Nam-D'Agostino goodness-of-fit (GND) statistic overall and in subgroups by race, natal sex, and Global Burden of Disease region. Small GND p-value indicates poor calibration. Results: Participants were mean age 50 years, 31% female, 65% nonwhite, with a median (Q1, Q3) 10-yr PCE risk of 4.5% (2.2, 7.1). Overall, discrimination was moderate (C-statistic 0.72) and calibration was good (O:E events, 84:81, ratio 1.03, GND P=0.81). However, calibration demonstrated over-prediction of risk outside High Income regions. When restricted to High Income regions, under-prediction (O:E ratio>1.0) was suggested among females (2.56) and Black or African American participants (1.66). Conclusion: Among a global cohort of PWH with low-to-moderate traditional CV risk, the PCE was moderately effective to predict CV death, MI or stroke over 5 years but under-predicted events in females, Blacks or African Americans and participants from high-income regions. Performance in selected subgroups should be considered when using the PCE to guide prescribing statin therapy for CV prevention among PWH. The figure, table, or graphic for this abstract has been removed.

Poster Abstracts

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