It is important to recognize the marked differences in lipid effects induced by antiretroviral drugs and drug classes. For example, larger increases in total cholesterol, LDL-cholesterol, and triglycerides have been observed with first- vs second-generation protease inhibitors (PIs; eg, indinavir, lopinavir vs atazanavir, darunavir),10 whereas nonnucleoside reverse transcriptase inhibitors (eg, efavirenz) are associated with greater increase in total and LDL-cholesterol compared with newer PIs.11 Increased cardiovascular event risk has been linked to PIs and the nucleoside reverse transcriptase inhibitors (eg, abacavir and didanosine),10,29 and an increased risk for diabetes has been documented with some PIs and nucleoside reverse transcriptase inhibitors.30,31 In general, newer antiretroviral agents are associated with less lipid dysregulation.

Managing CVD Risk in HIV-Infected Persons


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The foremost objective in CVD risk mitigation in persons living with HIV is sustained viral suppression, decreasing systemic inflammation and moderately reducing CVD events.25 Consistent with this goal, the US Department of Health and Human Services guidelines recommend starting antiretroviral treatment in all HIV-infected persons, regardless of CD4 cell counts, to decrease inflammation and immune activation associated with cardiovascular and other end-organ damage.28 Lifestyle modification and management of traditional CVD risk factors, such as dyslipidemia and hypertension, are also major objectives, given the relatively high rates of these factors in individuals who are HIV positive.25

Selection of ART regimen should reflect the presence of comorbid conditions with possible substitution of a less atherogenic ART option to help mitigate CVD risk. For example, the guidelines note that improvements in triglyceride and LDL levels may occur by substituting atazanavir or atazanavir/ritonavir for lopinavir/ritonavir (Table 2).28

Table 2. ART-Associated Adverse Events That Can Be Managed With Substitution of Alternative Antiretroviral Agent

Switching from the thymidine analogs stavudine and zidovudine can prevent worsening lipoatrophy. Caution is warranted, however, when substituting alternative ART because of the possibility of drug failure, drug resistance, and poorer patient adherence. Therefore, any change of efficacious antiretroviral drug therapy should be implemented by specialists.

Although sparse, the data suggest that statins produce reductions in LDL-cholesterol in HIV-positive persons comparable to those in HIV-negative individuals;32,33 however, potential drug interactions with antiretroviral drugs must be considered. Please refer to the US Department of Health and Human Services guidelines for potential drug interactions between lipid-lowering drugs and antiretroviral agents.28

Drug interactions between the statins simvastatin, lovastatin, or atorvastatin and PIs or the nonnucleoside reverse transcriptase inhibitor efavirenz may occur as a result of hepatic metabolism via the CYP450 3A4 isoenzyme system.34 Interactions with PIs and fluvastatin or (to a lesser extent) rosuvastatin are also possible because metabolism is via CYP 2C9. Use of lovastatin or simvastatin with all PIs and efavirenz should be avoided; initiation of the lowest dosage and careful monitoring are warranted if atorvastatin, fluvastatin, or rosuvastatin are coadministered with PIs.25 In general, pravastatin is an attractive option in HIV-infected persons who are candidates for statin therapy because it is not significantly metabolized via the CYP isoenzyme system and some persons with HIV may require higher doses of statins to manage dyslipidemia.

Recommendations for the management of hypertension are similar in HIV-positive and HIV-negative individuals with careful monitoring of potential drug interactions.28,35 European guidelines describe drug sequencing for hypertension.36 Please refer to the European AIDS Clinical Society guidelines for potential drug interactions between antihypertensive drugs and antiretroviral agents, including drugs that should not be coadministered.36

Conclusion

In sum, persons living with HIV infection have a higher risk for CVD, and use of some antiretroviral agents can exacerbate this risk. However, achieving sustained viral suppression with antiretroviral therapy has massive HIV-related benefits, including a reduction in inflammatory markers, which more than offset any marginally increased CVD risk. To achieve optimal care in HIV-infected persons, traditional risk factors for CVD should be managed appropriately, whereas antiretroviral drug therapy can be tailored to the specific patient’s needs and risk for CVD and other comorbidity.

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References

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