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CLINICAL STATEMENTS AND GUIDELINES

August 29, 2023 Circulation. 2023;148:e9–e119. DOI: 10.1161/CIR.0000000000001168

Virani et al 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline

recommends that chronic inflammatory conditions be considered risk-enhancing factors that should guide clinician-patient risk discussion for cholesterol management.13 Patients with HIV have a higher risk of CAD and MI compared with age- and sex-matched controls.14 The increased risk may be attributable to HIV itself, the antiretroviral therapy,15 and to a higher prevalence of traditional, modifiable risk factors.6 Newer generation antiretroviral therapy regimens have more favorable lipid effects and are associated with improvements in subclinical markers of atherosclerosis. Similarly, although new treatments for autoimmune diseases, including rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematous, and inflammatory bowel diseases, can negatively affect lipid profiles, adequate control of disease activity with steroid-sparing agents should be prioritized and may help lower cardiovascular risk.10 Because of the rapidly changing and complex pharmacological landscape in treating HIV and other chronic inflammatory conditions, patients should receive care from a multidisciplinary care team that includes infectious disease, rheumatology expertise, or both.

Recommendation-Specific Supportive Text

1 The SMART (Strategies for Management of

Antiretroviral Therapy) trial showed that, compared with continuous use of antiretroviral therapy, episodic use of antiretroviral therapy increased risk of opportunistic disease and death from any cause, including CVD.1 The MI event rate was 1.3 per 100 person-years in the interruption arm versus 0.8 per 100 person-years in the continuous use of antiretroviral therapy arm. Higher CD4 cell count and lower HIV RNA levels are associated with a lower risk of ASCVD.6,16,17

2 Excess cardiovascular risk in patients with HIV may

be partly attributable to side effects from antiretroviral therapy, including adverse effects on lipid levels. In adults with CCD and HIV, it is reasonable to choose newer generation antiretroviral treatment regimens associated with more favorable lipid and cardiovascular risk profiles.3–5 These include protease inhibitor regimens with lower doses of ritonavir for boosting and using atazanavir-ritonavir–containing regimens (see Table 23 for commonly used antiretroviral therapy drugs and the effect on lipid levels). In 1 randomized study, switching from a ritonavir-boosted protease inhibitor to a dolutegravir-based regimen was noninferior in maintaining a viral suppression with improvement in lipid levels (7.7% LDL-C reduction).3 Contemporary US guidelines recommend that individuals with HIV and CVD should switch from an abacavir-containing regimen because of its possible association with increased cardiovascular events.4,18 Drug interactions are common among patients with HIV on antiretroviral therapy, which should be considered when starting or intensifying statin therapy for management of CCD.6,7,19,20 Although pravastatin and pitavastatin are least likely to interact with antiretroviral therapy, rosuvastatin and atorvastatin may be preferred for more intense LDL-C reduction in patients with HIV and CCD.20,21 Management of hypertriglyceridemia in patients with CCD and HIV should follow standard treatment pathways.22

Table 23.  Common Antiretroviral Therapy Drugs and Effects on Lipid Levels Class Drug Effect on Blood Lipids Protease inhibitors Atazanavir Increases HDL-C and decreases LDL-C levels

Darunavir Increases HDL-C levels Fosamprenavir Hypertriglyceridemia Ritonavir* Increases HDL-C levels Saquinavir Neutral Tipranavir Dyslipidemia

NRTIs Abacavir Increases total cholesterol, LDL-C, and HDL-C levels

Lamivudine Increases total cholesterol, LDL-C, and HDL-C levels Tenofovir fumarate disoproxil Lowers LDL levels Zidovudine Hypertriglyceridemia

NNRTIs Efavirenz Increases total cholesterol, LDL-C, HDL-C, and triglyceride levels

Nevirapine Neutral or decreases lipid levels Rilpivirine Neutral

Integrase inhibitors Dolutegravir Neutral

Raltegravir Increases HDL levels

*Although ritonavir is a protease inhibitor, this drug is generally used as a pharmacokinetic enhancer. HDL indicates high-density lipoprotein; HDL-C, high-density lipoprotein cholesterol; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; NNRTI, nonnucleoside reverse-transcriptase inhibitor; and NRTI, nucleoside reverse-transcriptase inhibitor.

Adapted from Hsue PY et al.6 by permission from Springer Nature, Copyright 2019.

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