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TOP SECRET > B P9 C85 Cardiovascular Abnormalities in HIV-Infected Individuals > Flashcards

B P9 C85 Cardiovascular Abnormalities in HIV-Infected Individuals Flashcards

1
Q

The onset of HIV infection associates with a _____.

A

Decrease: TC, LDL, HDL
Increase: TG

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2
Q

As a general rule, PIs, non- nucleoside reverse transcriptase inhibitors (NNRTIs), and nucleoside reverse transcriptase inhibitors (NRTIs) increase _____ levels and may increase _____ levels.

A

Increase TG levels
May increase LDL-C levels

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3
Q

PIs increase triglyceride levels; in particular, _____ can cause extreme hypertriglyceridemia exceeding 1000 mg/dL.

A

Ritonavir

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4
Q

_____, either alone or in combi- nation with ritonavir, associates less with an increase in triglycerides compared with these other PIs.

A

Atazanavir

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5
Q

Older PIs such as _____ also increase LDL-C, probably by increasing intestinal cholesterol absorption and not by increased synthesis.

A

Ritonavir

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6
Q

Among NNRTIs, _____ associates with slightly more subjects developing hypercholesterolemia and hypertriglyceridemia in one study compared with nevirapine.

A

Efavirenz

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7
Q

_____ can associate with greater increases in LDL-C but not total to HDL-C ratio compared with atazanavir-ritonavir.

A

Efavirenz

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8
Q

The newer NNRTI _____ generally associates with lower total, HDL-C, LDL-C, and triglyceride levels than efavirenz.

A

Rilpivirine

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9
Q

The NRTI _____,a newer formulation of tenofovir disoproxil fumarate (TDF), is associated with higher levels of LDL-C and HDL-C but similar total cholesterol to HDLC ratios compared with TDF.

A

Tenofovir alafenamide

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10
Q

The integrase strand transfer inhibitors (INSTIs), _____ ,and the C-C chemokine receptor type 5 coreceptor antagonist __ have favorable effects on lipids, particularly com- pared with older forms of ART.

A

INSTIs: Raltegravir, Elvitegravir, and Dolutegravir

C-C chemokine receptor type 5 coreceptor antogonist: MARAVIROC

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11
Q

Switching from a ritonavir-boosted PI regimen to _____ can reduce triglyceride levels.

A

Darunavir/cobicistat

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12
Q

High probability of adverse effects on Lipid levels with the following HIV drugs:

A

PI:
Lopinavir/Ritonavir
Tipranavir/Ritonavir
Indinavir/ritonavir

NRTI: Stavudine

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13
Q

_____ is a syndrome characterized by fat accumulation in the dorsocervical region and an increase in or preservation of visceral fat, with subcutaneous and peripheral fat loss, resulting in relative central adiposity

A

Lipodystrophy

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14
Q

Early PIs and the NRTIs _____ associated with lipodystrophy in at least 20% to 35% of persons taking these drugs long term, but newer PIs such as atazanavir do not appear to induce lipodystrophy.

A

Stavudine and Didanosine

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15
Q

Development of the metabolic syndrome was common in the first _____ years after initiation of an ART regimen that included stavudine or lopinavir/ritonavir, but is less common with newer drugs.

A

First 3 years

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16
Q

The PIs _____ and the thymidine analogue _____ can cause insulin resistance

A

PI: Indinavir and lopinavir/ritonavir
TA: Stavudine

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17
Q

The development of CKD in persons with previously normal renal function has been reported with some forms of ART; specifically, ___ and the PIs _____.

A

TDF

PIs (atazanavir/ritonavir and lopinavir/ritonavir)

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18
Q

The pathogenesis of atherosclerosis in the setting of HIV infection is complicated and incompletely understood. Contributing mechanisms include the _____

A

(1) Effects of the HIV proteins on immune and vascular cells
(2) Immunodeficiency caused by the HIV infection
(3) Co-infection with cytomegalovirus (CMV)
(4) Translocation of microbial products from the gut
(5) Chronic inflammation
(6) Immune activation

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19
Q

The HIV envelope protein _____ can stimulate endothelin-1 production.

A

gp120

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20
Q

HIV-encoded proteins such as _____ induce inflammation and endothelial dysfunction

A

Transactivator of transcription (Tat)
Negative factor (Nef)

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21
Q

_____ is the hallmark of HIV infection, and nadir CD4+ T cell count is a rough marker of the severity of immunodeficiency.

A

CD4+ T cell depletion

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22
Q

Nadir CD4+ T cell count has been linked to increased _____,increased _____,and incident ____.

A

Increased carotid intima-media thickness (IMT)
Increased arterial stiffness
Incident MI

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23
Q

Co-infection with _____ might play a part in HIV-associated atheroclerosis

A

CMV

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24
Q

CMV co-infection links strongly to _____ and may also have a role in chronic immune activation and inflammation by expansion of the HIV reservoir.

A

HIV viral persistence

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25
Q

Plasma levels of markers of microbial translocation such as _____ independently predict HIV disease progression and mortality in individuals not receiving ART

A

Soluble CD14 and LPS

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26
Q

HIV infection associates with high plasma levels of inflammatory and coagulation markers, specifically _____, and these biomarkers strongly predict CV events and all-cause mortality in individuals with HIV infection

A

CRP
IL-6
D-dimer

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27
Q

Inflammation is a therapeutic target to reduce CV events in individuals with or without HIV infection. _____ therapy reduces inflammation, but the effects on inflammatory markers seem to be attenuated in the presence of HIV infection

A

Statin

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28
Q

_____, a monoclonal antibody targeting IL-1β, reduces CV events in patients with previous MI and a high-sensitivity CRP level of ≥2 mg/L.

A

Canakinumab

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29
Q

The inflammatory phenotype is characterized by higher levels of:

A

CRP
IL-6
D-dimer

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30
Q

The cardiac cluster/phenotype comprises higher levels of:

A

Protein ST2 (aka IL-1 receptor-like 1)
N-terminal pro-B-type natriuretic peptide
Growth/ differentiation factor 15

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31
Q

Diastolic dysfunction is common with the _____ cluster of biomarkers, and pulmonary hypertension (PH) is more common in the _____ cluster

A

Diastolic dysfunction: inflammatory
Pulmonary hypertension: cardiac

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32
Q

The most obvious mechanism by which ART increases atherosclerosis is by _____.

A

Worsening blood lipid levels

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33
Q

Interestingly, even after adjustment for blood lipid levels in the large D:A:D study, cumulative exposure to the NRTIs ______ or to the PIs _____ associated with an increased risk of MI.

A

NRTI: Abacavir/Didanosine
PI: Lopinavir-ritonavir or Indinavir

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34
Q

CT angiographic studies reveal that _____ plaques are much more common in persons living with HIV than in uninfected controls

A

Noncalcified plaques

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35
Q

ACS in HIV: Their risk scores tend to be (lower/higher), and they are more likely to have ____vessel coronary artery disease

A

Risk scores: Lower
CAD: single-rather than multiple-vessel

36
Q

In earlier studies, people with HIV had substantially _____ rates of restenosis after percutaneous coronary interventions with bare metal stents, compared with uninfected individuals

A

Higher

37
Q

Thus, whereas treatment was initially restricted to those with low CD4 counts, it is now widely accepted that treatment should be started in all individuals with HIV infection with detectable viremia irrespective of _____.

A

CD4 cell count

38
Q

Initiation of ART is recommended as soon as possible in the setting of acute HIV infection because initiation prior to the development of HIV antibody positivity _____.

A

(1) reduces the size of the latent HIV reservoir
(2) reduces immune activation
(3) may protect against infection of central memory T cells

39
Q

The _____ have moved into a key role as first-line therapy because they are highly effective, with higher and more rapid rates of virologic suppression compared with PIs and NNRTIs, the previous mainstays of ART.

A

INSTIs

40
Q

Statin contraindicated with the concomitant use of PIs and NNTRIs

A

Simvastatin

Lovastatin

41
Q

Potent statins in the treatment of dyslipidemia in ART

A

Atorvastatin
Rosuvastatin

42
Q

Statin with the least drug-drug interaction with ART

A

Pitavastatin

43
Q

Monitoring of kidney function with eGFR, urinalysis, and testing for glycosuria and albuminuria or proteinuria is recommended when ART is initiated or changed and every ____ months

A

6 months

44
Q

Recommendations for laboratory monitoring include as close to the time of HIV diagnosis as possible and before beginning ART, measurement of:

A

CD4 cell count
plasma HIV RNA level
Serologic studies for hepatitis A, B, and C
Serum chemistries
ECC
Complete blood cell count
Urine glucose and protein
Genotyping for resistance to reverse transcriptase and PI

45
Q

_____ should form the foundation for treatment of lipids in persons living with HIV.

A

Diet and lifestyle optimization

46
Q

In one report, fasting triglyceride levels and adipose tissue mass decreased, and muscle mass increased in HIV-infected men with hypertriglyceridemia after 16 weeks of _____.

A

Resistance training

47
Q

This trial show that pitavastatin calcium lowers the incidence rate of heart disease events by 35% in people with HIV.

A

REPRIEVE Trial

48
Q

These guidelines also state that statin therapy should be considered to achieve the target LDL-C level of _____, the same target that is recommended for other patients at high risk of CVD.

A

< 2.6 mmol/L (100 mg/dL)

49
Q

The 2018 updated ACC/AHA guidelines state that HIV infection can be considered a CVD risk enhancer, which would favor starting _____ statin therapy

A

Moderate-intensity or high- intensity

50
Q
A
51
Q

The 2018 updated ACC/AHA guidelines also recommend that a risk assessment, including fasting lipid profile, be done _____ after starting ART.

A

Before and 4 to 12 weeks

51
Q

Lovastatin and simvastatin are contraindicated with PIs because of the risk of _____ from high statin blood levels

A

Rhabdomyolysis

51
Q

Due to the risk of rhabdomyolysis, no more than ___mg/day of atorvastatin should be used for individuals taking ritonavir-boosted PIs.

A

40mg/day

52
Q

Rosuvastatin blood levels increase when used with atazanavir/ritonavir and lopinavir/ritonavir, so limiting the rosuvastatin dose to __mg is advisable with these drugs

A

10mg

53
Q

Despite a lack of clinical trial outcomes data, _____ is a good choice for individuals living with HIV because at higher doses its LDL-C– lowering effect is moderate, and because its metabolism is via glucuronidation, drug-drug interactions are avoided

A

Pitavastatin

54
Q

In individuals with HIV who do not tolerate statins, ____- is a safe option, albeit with limited LDL-C–lowering potency.

A

Ezetimibe

55
Q

Fibrates reduce triglycerides, often at low doses, but have a drug-drug interaction with statins and some types of ART; for example, the lopinavir-ritonavir PI combination greatly reduces _____ absorption

A

Gemfibrozil

56
Q

_____ found in fish oil reduce triglyceride levels in persons with HIV and hypertriglyceridemia and has the advantage of no important drug-drug interactions; however, some fish oil preparations increase LDL-C levels modestly.

A

Omega-3 fatty acids

57
Q

This trial tested the effect of icosapent ethyl, a purified and quality-controlled pharmaceutical-grade eicosapentaenoic acid preparation, 2 g twice daily as add-on therapy with statins in 8179 patients with CVD or diabetes and other CV risk factors, and a fasting triglyceride level of 150 to 499 mg/dL

A

The Reduction of Cardio- vascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT)

58
Q

The 2019 AHA statement recommends consideration of selected CV risk enhancers identified in the 2018 ACC/AHA cholesterol clin- ical practice guidelines as likely atherosclerotic cardiovascular dis- ease (ASCVD) risk enhancers in HIV . These include:

A

(1) Early family history of MI or stroke (men, age <55 years; women, age <65 years)
(2) Persistently elevated LDL-C ≥160 mg/dL
(3) CKD
(4) Preeclampsia or premature menopause
(5) Subclinical atherosclerosis on imaging (including CAC)
(6) High levels of selected biomarkers associated with elevated CV risk independently of traditional risk factors, specifically lipoprotein(a), CRP, and apolipoprotein B

59
Q

Of note, the ACC/AHA guidelines failed to recommend statin in more than two-thirds of HIV-infected individuals with evidence of carotid plaque _____.

A

> 1.5 mm

60
Q

A revised definition of PH proposed in 2018 included:

A

(1) mPAP > 20 mm Hg
(2) PA wedge pressure of 15 mm Hg or less
(3) PVR 3 Wood units or higher

61
Q

The pathology of PH associated with HIV infection is similar to that seen in PH patients without HIV. It includes _____ of small pulmonary arteries with plexogenic lesions in the media, leading ultimately to obstruction of small pulmonary arteries.

A

Intimal thickening

62
Q

Levels of inflammatory markers such as _____ increase in HIV-associated PH.

A

VEGF-A
PDGF
IL-1 and IL-6

63
Q

Death in PH-HIV is usually sudden or due to _____ and is rarely due to other HIV complications

A

Right HF

64
Q

Predictors of survival in PH-HIV were:

A

CI > 2.8 L/min/m2
CD4 count > 200 cells/μL

65
Q

Echocardiographic screening for PH is now recommended independent of symptoms for individuals with HIV and one of the following risk factors:

A

Female sex
IV drug or cocaine use
Hepatitis C infection
High-prevalence country of origin
Known Nef or Tat HIV proteins
African-American patients

66
Q

_____ is the reference standard for the diagnosis of PH and must be performed before the initiation of PH-specific treatment

A

Right heart catheterization

67
Q

Routine vasodilator testing is not recommended in patients with PH-HIV because a _____.

A

Positive vasodilator test is rarely found

68
Q

Treatment of PH-HIV is similar to treatment of PH in the absence of HIV, except for the issue of ____

A

Drug-drug interactions between PH therapy and ART

69
Q

The recommended dose of bosentan for individuals taking PIs is _____.

A

62.5 mg/ day or every other day instead of the usual dose of 125 mg twice daily

70
Q

The pathophysiology of HIV-associated cardiomyopathy is multifactorial, with proposed causes including:

A

(1) direct HIV infection with or without myocarditis
(2) co-infection with other viruses such as Coxsackie virus B3 and CMV
(3) opportunistic infections
(4) nutritional disorders

71
Q

Proinflammatory cytokines such as _____ also depress LV systolic function.

A

TNF and IL-1β

72
Q

One ART, ___, might reduce the risk of developing HF: in a large cohort of US veterans with HIV, HF risk was markedly lower in current users

A

TDF

73
Q

TDF might reduce the risk of HF by _____ and thus decreasing inflammation.The potential beneficial effect of TDF in HF requires confirmation.

A

Improving viral control

74
Q

In a cohort study from New York, with poorly controlled HIV and a high prevalence of drug use, PI-based regimens were associated with _____ among HIV-infected individuals with HF.

A

Lower LV ejection fraction
Higher pulmonary artery systolic pressure
Increased CV mortality, 30-day HF readmission

75
Q

In one study, _____ on cardiac MRI, a marker of cardiac fibrosis, was detected in 83% of 103 HIV subjects compared with only 16% of 92 controls

A

Late gadolinium enhancement

76
Q

Markers of HIV disease severity, specifically _____, independently associate with the development of AF, along with expected clinical factors such concomitant coronary disease, HF, alcoholism, renal dysfunction, and hypothyroid- ism.

A

Low CD4 count and high viral load

77
Q

As in the general population, management of AF aims to _____.

A

Control the ventricular rate
Prevent embolic events

78
Q

Drugs used for rate control (_____) and newer anticoagulants (_____) are metabolized by the CYP3A4 hepatic metabolism and thus interact with ART.

A

Verapamil, Diltiazem

Apixaban, Rivaroxaban, Ticagrelor

79
Q

_____, especially in the presence of detectable HIV RNA levels, predicted sudden cardiac death

A

LV systolic dysfunction and diastolic dysfunction

80
Q

HIV stroke patients tend to be _____. Risk factors for ischemic stroke in the general population (i.e., hypertension, diabetes, smoking and dyslipidemia) are also risk factors for stroke in the setting of HIV.

A

Younger and male

81
Q

A _____ may associate with intracerebral hemorrhage.

A

Low CD4 count

82
Q

More than one-third of strokes in persons with HIV are intracranial, as opposed to extracranial origin. HIV crosses the blood-brain barrier early in the course of the infection and promotes inflammation of _____

A

Small vessels

83
Q

During the first _____ months of ART in immunosuppressed individuals, the risk of stroke increases, perhaps due to small vessel thinning and erosion due to remodeling and neuroinflammation.

A

6 months

84
Q

A _____ increase the risk of stroke

A

High viral load and a low CD4 count

85
Q

Pragmatic approach to atherosclerotic cardiovascular disease (ASCVD) risk assessment and prevention in treated HIV infection

A

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