Plasma LAG3 and subclinical coronary artery disease in the Multicenter AIDS Cohort Study
S Sarkar1, S Haberlen2, WS Post3, T Kelesidis4, D Wiley5, L Kingsley6, S Wolinsky7, A Rodriguez Oquendo8, TT Brown1
1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; 2Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; 3Division of Cardiology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland; 4Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California; 5School of Nursing, University of California, Los Angeles, California; 6Departments of Infectious Diseases and Microbiology and Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania; 7Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; 8Center for Vascular Biology, University of Connecticut Health Center, Farmington, Connecticut
Objectives: The objectives of this study were 1) to determine whether plasma LAG3, a T-cell inhibitor associated with cardiovascular disease in the general population, differed by HIV serostatus and 2) to ascertain whether LAG3 was associated with moderate to severe coronary artery stenosis, independent of systemic inflammation, in the Multicenter AIDS Cohort Study (MACS).
Methods: Plasma specimens collected 12 ±8 months before coronary CT angiography were tested for LAG3 in men enrolled in the MACS Cardiovascular Sub-study. LAG3 was natural log transformed to correct for skewness and to fit a normal distribution. Multi-variable linear regression was used to determine if HIV serostatus was associated with loge LAG3 concentrations, independent of age, race, study center, systolic blood pressure, antihypertensive medication use, diabetes medication use, fasting glucose, HDL and total cholesterol, lipid lowering medication use, body mass index and smoking status (current, former or never). Multivariable logistic regression estimated the odds of moderate to severe coronary artery stenosis related to each loge increase in LAG3 concentrations, independent of demographic and cardiovascular risk factors, as well as systemic inflammation biomarkers (IL-6, ICAM-1, sTNFαRI, sTNFαRII, sCD163 and sCD14). In models that included only men with HIV, HIV-associated variables were included as follows: history of an AIDS defining malignancy or opportunistic infection, current and nadir CD4+ T-cell count, current viral load and ART use duration.
Results: 58% (410/704) of the study participants were men with HIV, who were younger (mean age 52 versus 55 years) and less often reported non-Hispanic White race (50% versus 69%) than men without HIV. In a univariate analysis, median (interquartile range [IQR]) LAG3 in men with HIV (7.1 pg/ml [natural log transformed; 6.4,8.1]) was lower than in men without HIV (7.5 [6.7–7.3]; P<0.01). However, in a model adjusted for covariates, HIV serostatus was not significantly associated with loge LAG3 concentrations. Greater age was associated with greater loge LAG3 concentrations (P<0.01). Non-Hispanic Black race and current smoking status were associated with lower loge LAG3 concentrations (P<0.05 for both). In a model that included only men with HIV, current antiretroviral (ART) therapy use was associated with lower loge LAG3 concentrations (P=0.04). In adjusted models with and without inflam-matory markers, no significant association between loge LAG3 concentrations and moderate to severe coronary stenosis was observed.
Conclusion: Despite biological plausibility and previous studies in the general population that showed the association of plasma LAG3 with CVD, we did not detect any association between LAG3 concentrations and either HIV serostatus or significant subclinical atherosclerosis.
Abstract P12
Antiviral Therapy 2020; 25 Suppl 1:A40
Risk factors for severe hypertriglyceridaemia in people living with HIV in Guatemala
DW Ortíz1, HE Marroquin1, L Larson2, KB Franco1, A Spec2, JR Melendez1, R Pinzón1, AJ Samayoa1, C Mejia-Chew2, JA O'Halloran2
1Unidad de Atención Integral de VIH e Infecciones Crónicas “Dr. Carlos Rodolfo Mejía Villatoro”, Hospital Roosevelt, Guatemala; 2Department of Medicine, Division of Infectious Diseases, Washington University in Saint Louis
Objectives: Hypertriglyceridaemia is more prevalent in the Hispanic population living in the US and in Latin America in general. People living with HIV (PLWH) have increased risk of hypertriglyceridaemia due to antiretroviral therapy (ART) effects. Adverse health outcomes correlate with triglyceride levels and aggravation of this condition into severe hypertriglycer-idaemia demands aggressive treatment. Severe hypertriglyceridaemia lacks comprehensive data sets in PLWH describing the condition and its risk factors. We aimed to identify risk factors for severe hypertriglyceridae-mia in PLWH receiving care at Hospital Roosevelt in Guatemala.
Methods: Baseline data from a prospective cohort study of PLWH enrolled between July 2019 and March 2020 was analysed. We included PLWH 18 years of age or older receiving ART over the last 6 months. Severe hypertriglyceridaemia was defined as fasting serum triglycerides >500 mg/dl from a lipid panel taken up to 4 months before or 1 month after enrolment. Demographics, alcohol use, smoking, history of comorbidi-ties, HIV parameters (CD4 and viral load history), anthropometrics and ART at enrolment were compared based on severe hypertriglyceridaemia using univariable analysis; variables with a P<0.03 were included in a multivariable regression model.
Results: Of 673 participants included, 54.7% were males with a median age of 40 years (IQR 32–49) and 106 (15.8%) had indigenous background. Severe hypertriglyceridaemia was identified in 35 (5%) cases. The majority of ART regimens were efavirenz-based (396, 58.8%), dolutegravir-based (162, 24.1%), lopina-vir/ritonavir-based (73, 10.8%), nevirapine-based (32, 4.7%) accounting for 98% of ART prescribed. In the univariable analysis, male gender, diabetes, high waist to stature ratio (WTS) and efavirenz-based current ART were all associated with severe hypertriglyceridaemia and were included in the multivariable analysis (Table 1). Dolutegravir was associated with not having severe hypertriglyceridaemia (OR 0.29, 95% CI 0.087, 0.95; P=0.043). All variables included in the multivariable analysis were associated with severe hypertriglyceridae-mia, with a relative higher risk conferred by high WTS and diabetes (Table 1).
(Abstract P12)
Table 1. Univariable and multivariable logistic regression of 673 people living with HIV with and without severe hypertriglyceridemia at a large HIV clinic in Guatemala.
Discussion: To our knowledge, this is the first study assessing demographic and clinical variables with severe hypertriglyceridaemia in PLWH in the region. Severe hypertriglyceridaemia has been associated with male gender and diabetes in other studies, consistent with the findings of this cohort. While both protease inhibitors and efavirenz have been linked with severe hypertriglyceridaemia, in our cohort only efavirenz had a significant association with this outcome. This may be related to specific genetic and metabolic profiles for our population, specifically regarding variations in the cytochrome P450 enzymes. However, further studies are needed to evaluate the effect severe hypertriglyceridaemia has on cardiovascular risk in this cohort.
Abstract P13
Antiviral Therapy 2020; 25 Suppl 1:A42
Predictors of atherosclerosis in people with HIV who do not currently qualify for statin therapy
MA Moso1, JM Trevillyan1,2, A Dart3, L Dewar3, JF Hoy1,2
1Department of Infectious Diseases, Alfred Health, Melbourne, Australia; 2Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia; 3Department of Cardiology, Alfred Health, Melbourne, Australia
Objectives/aim: People with HIV are at increased risk for cardiovascular disease (CVD). This study aimed to describe factors associated with atherosclerosis in people with HIV who do not currently qualify for statin therapy.
Methods: Participants with controlled HIV (suppressed viral load, antiretroviral therapy for >6 months) who were at moderate cardiovascular risk (10-year Framingham risk score 10–15%) with no indication for statin therapy were recruited from a single centre in Australia and 4 centres in Switzerland. All participants had carotid intima media thickness (cIMT) measured, a physical exam and fasting bloods. Elevated cIMT was defined as >1.0 mm and is indicative of subclinical carotid atherosclerosis.
Results: Participants (n=83) were predominantly Caucasian (88%), male (99%), with a median age of 54 years (IQR 50–58). 27 (32.5%) were current smokers, 26 (31%) had a positive family history of CVD and 23 (27%) had been previously diagnosed with hypertension. All participants were on antiretroviral therapy with a suppressed viral load. Median CD4 cell count was 610 cells/ul (IQR 417–761). The median cIMT at the common carotid artery was 0.7 mm (IQR 0.6–0.8). cIMT correlated with age, high-density lipo-protein (HDL) cholesterol, albumin and high sensitivity C-reactive protein, with non-significant trends towards correlation with IL-6 and platelet count. Ten (12%) participants had a cIMT >1.0 mm. Factors associated with a cIMT >1.0 mm included total cholesterol (OR 2.3, P=0.035), low-density lipoprotein cholesterol (OR 2.5, P=0.046), HDL cholesterol (OR 13.9, P=0.027) and current abacavir use (OR 6.9, P=0.007).
Conclusion: In people with well controlled HIV, dyslipidaemia and exposure to abacavir is associated with an increase in atherosclerosis and cardiovascular risk.
Abstract P14
Antiviral Therapy 2020; 25 Suppl 1:A43
Impact of rosuvastatin on pulse wave velocity (PWV) in men with HIV at moderate cardiovascular risk; a sub-study of a multinational, randomized, double blind, placebo-controlled trial
V Hall1, JM Trevillyan1,2, A Dart3, L Dewar3, JF Hoy1,2
1Department of Infectious Diseases, Alfred Health Melbourne, Australia; 2Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia; 3Department of Cardiology, Alfred Health, Melbourne, Australia
Aim: People with HIV are at increased risk for cardiovascular disease (CVD). This substudy aimed to determine the effect of rosuvastatin on PWV in HIV.
Methods: Men with well controlled HIV (VL<20, ART for >6 months) at moderate cardiovascular risk (10-year Framingham risk score 10–15%) and no indication for statins (n=55) were randomized 1:1 to rosuvastatin (n=28) or matched placebo (n=27). Participants had PWV, carotid intima media thickness and fasting bloods at baseline, week 48 and 96. The primary end point was change in PWV from baseline to week 96. Factors associated with baseline PWV were evaluated.
Results: Participants were predominantly Caucasian (50 [90.9%]), median age 54 years (IQR 51–58). Seventeen (30.9%) were smokers, median systolic blood pressure 130 mmHg (IQR 120–135). Baseline variables were well matched across the arms. There was no difference in change in PWV from baseline to week 96 between the arms; rosuvastatin =0.4 m/s (IQR -0.1–1.0) versus placebo =0.4 m/s (IQR -0.2–1.2); P=0.92. Rosu-vastatin led to significant reductions in total cholesterol (-1.3 mmol/l [-1.7–-0.9] versus placebo =0.0 [-0.5–0.4]; P<0.001). Baseline PWV was associated (P<0.05) with age, smoking, body mass index and intima media thickness but not with cell count or CD4 nadir. Non-severe events were more frequent with rosuvastatin. Two participants developed new type 2 diabetes, four experienced a CVD event and one an asymptomatic raise in CK to 9,000; all in the rosuvastatin arm.
Conclusions: In men with HIV at moderate CVD risk rosuvastatin had no effect on PWV but was associated with significant side effects.
Abstract P15
Antiviral Therapy 2020; 25 Suppl 1:A44
One-year statin persistence and adherence in adults with HIV in the United States
KB Crockett1, Y Wen2, ET Overton3, EA Jackson4, RS Rosenson5, P Muntner2, LD Colantonio2
1Department of Health Care Organization and Policy, School of Public Health, University of Alabama at Birmingham, AL, USA; 2Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, AL, USA; 3Division of Infectious Diseases, School of Medicine, University of Alabama at Birmingham, AL, USA; 4Division of Cardiovascular Disease, School of Medicine, University of Alabama at Birmingham, AL, USA; 5Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Background: Statin persistence and adherence are low among US adults. Many adults with HIV have high cardiovascular disease risk and may benefit from statin therapy. Most individuals with HIV in the US have high adherence to antiretroviral therapy (ART) but less is known about their statin persistence and adherence. We compared statin persistence and adherence between adults with and without HIV. Statin adherence was compared with ART adherence among adults with HIV.
Methods: We analysed claims data from adults in the MarketScan database who initiated statin therapy between 2007 and 2016. People with HIV (n=5,619) were frequency matched 1-to-4 to those without HIV (n=22,476) based on age, sex and calendar year of statin initiation. Statin persistence was defined by having dispensed statin medication during the last 90 days of the 365 days following initiation. High statin adherence was defined as proportion of days covered (PDC) ≥80% during the 365 days following initiation. The minimum PDC was calculated for all ART drugs among people with HIV.
Results: The mean age of the study population was 51 years and 85.8% were men. Statin persistence was higher among adults with versus without HIV (72.8% versus 65.2%, multivariable-adjusted prevalence ratio 1.13, 95% CI 1.11, 1.15). Among those who were persistent, a higher proportion of people with versus without HIV had high statin adherence (69.6% versus 59.9%, multivariable-adjusted prevalence ratio 1.16, 95% CI 1.13, 1.19). Among people with HIV and high ART adherence (PDC≥0.90), 34.6% had a PDC for statin therapy <0.80.
Conclusions: A high proportion of adults with HIV have low adherence to statin therapy. Patient-centred approaches are needed to increase statin adherence among people with HIV.
