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

Continue Reading

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


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.

Related Articles


  1. Islam FM, Wu J, Jansson J, Wilson DP. Relative risk of cardiovascular disease among people living with HIV: a systematic review and meta-analysis. HIV Med. 2012;13:453-468. doi: 10.1111/j.1468-1293.2012.00996.x
  2. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007;92:2506-2512. doi: 10.1210/jc.2006-2190
  3. Durand M, Sheehy O, Baril JG, Lelorier J, Tremblay CL. Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: a cohort and nested case-control study using Quebec’s public health insurance database. J Acquir Immune Defic Syndr. 2011;57:245-253. doi: 10.1097/QAI.0b013e31821d33a5
  4. Data Collection on Adverse Events of Anti-HIV drugs (D:A:D) Study Group, Smith C, Sabin CA, Lundgren JD, et al. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D study. AIDS. 2010;24:1537-1548. doi: 10.1097/QAD.0b013e32833a0918
  5. Glass TR, Ungsedhapand C, Wolbers M, et al; Swiss HIV Cohort Study. Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study. HIV Med. 2006;7:404-410. doi: 10.1111/j.1468-1293.2006.00400.x
  6. Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA. 2003;289:2978-2982. doi: 10.1001/jama.289.22.2978
  7. Grunfeld C, Pang M, DoerrlerW, Shigenaga JK, Jensen P, Feingold KR. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992;74:1045-1052. doi: 10.1210/jcem.74.5.1373735
  8. Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren J, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283-2296. doi: 10.1056/NEJMoa062360
  9. Subramanian S, Tawakol A, Burdo TH, et al. Arterial inflammation in patients with HIV. JAMA. 2012;308:379-386. doi: 10.1001/jama.2012.6698
  10. Molina JM, Andrade-Villanueva J, Echevarria J, et al; CASTLE Study Team. Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study. J Acquir Immune Defic Syndr. 2010;53:323-332. doi: 10.1097/QAI.0b013e3181c990bf
  11. Daar ES, Tierney C, Fischl MA, et al; AIDS Clinical Trials Group Study A5202 Team. Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1. Ann Intern Med. 2011;154:445-456. doi: 10.7326/0003-4819-154-7-201104050-00316
  12. Grunfeld C, Rimland D, Gibert CL, et al. Association of upper trunk and visceral adipose tissue volume with insulin resistance in control and HIV-infected subjects in the FRAM study. J Acquir Immune Defic Syndr. 2007;46:283-290. doi: 10.1097/QAI.0b013e31814b94e2
  13. Centre of Excellence for Health, Immunity, and Infections (CHIP). Risk Assessment Tool System (RATS). Accessed February 1, 2017.
  14. Freiberg MS, Chang CC, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013;173:614-622. doi: 10.1001/jamainternmed.2013.3728
  15. Triant VA. Cardiovascular disease and HIV infection. Curr HIV/AIDSRep. 2013;10:199-206. doi: 10.1007/s11904-013-0168-6
  16. Alonso-Villaverde L. Fisiopatología de la enfermedad cardiovascular enpacientes con VIH [Physiopathology of cardiovascular disease in HIV infected patients]. Enferm Infecc Microbiol Clin. 2009;27(suppl 1):33-39. doi: 10.1016/S0213-005X(09)73443-3
  17. Zanni MV Abbara S, Lo J, Wai B, Hark D, Marmarelis E, Grinspoon SK. Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-Infected men. AIDS. 2013;27:1263-1272. doi: 10.1097/QAD.0b013e32835eca9b
  18. Hsue PY, Scherzer R, Hunt PW, et al. Carotid intima-media thickness progression in HIV-infected adults occurs preferentially at the carotid bifurcation and is predicted by inflammation. J Am Heart Assoc. 2012;1:e000422. doi: 10.1161/JAHA.111.000422
  19. Triant VA, Meigs JB, Grinspoon SK. Association of C-reactive protein and HIV infection with acute myocardial infarction. J Acquir Immune Defic Syndr. 2009;51:268-273. doi: 10.1097/QAI.0b013e3181a9992c
  20. Ford ES, Greenwald JH, Richterman AG, et al. Traditional risk factors and D-dimer predict incident cardiovascular disease events in chronic HIV infection. AIDS. 2010;24:1509-1517. doi: 10.1097/QAD.0b013e32833ad914
  21. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007;92:2506-2512. doi: 10.1210/jc.2006-2190
  22. High cholesterol facts. Centers for Disease Control and Prevention website. Updated March 17, 2015. Accessed February 12, 2017.
  23. Baekken M, Os I, Sandvik L, Oektedalen O. Hypertension in an urban HIV positive population compared with the general population: influence of combination antiretroviral therapy. J Hypertens. 2008;26:2126-2133. doi: 10.1097/HJH.0b013e32830ef5fb
  24. High blood pressure. Centers for Disease Control and Prevention website. Updated November 30, 2016. Accessed February 12, 2017.
  25. Hemkens LG, Bucher HC. HIV infection and cardiovascular disease. Eur Heart J. 2014;35:1373-1381. doi: 10.1093/eurheartj/eht528
  26. Grunfeld C, Saag M, Cofrancesco J Jr, et al; Study of Fat Redistribution Metabolic Change in HIV Infection (FRAM). Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy. AIDS. 2010;24:1717-1726. doi: 10.1097/QAD.0b013e32833ac7a2
  27. Scherzer R, Shen W, Bacchetti P, et al; Study of Fat Redistribution Metabolic Change in HIV Infection (FRAM). Simple anthropometric measures correlate with metabolic risk indicators as strongly as magnetic resonance imaging-measured adipose tissue depots in both HIV-infected and control subjects. Am J Clin Nutr. 2008;87:1809-1817.
  28. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Accessed February 3, 2017.
  29. Bavinger C, Bendavid E, Niehaus K, et al. Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review. PLoS One. 2013;8:e59551. doi: 10.1371/journal.pone.0059551
  30. De Wit S, Sabin CA, Weber R, et al; Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Diabetes Care. 2008;31:1224-1229. doi: 10.2337/dc07-2013
  31. Rasmussen LD, Mathiesen ER, Kronborg G, Pedersen C, Gerstoft J, Obel N. Risk of diabetes mellitus in persons with and without HIV: a Danish nationwide population based cohort study. PLoS One. 2012;7:e44575. doi: 10.1371/journal.pone.0044575
  32. Moyle GJ, Lloyd M, Reynolds B, Baldwin C, Mandalia S, Gazzard BG. Dietary advice with or without pravastatin for the management of hypercholesterolaemia associated with protease inhibitor therapy. AIDS. 2001;15:1503-1508.
  33. Bonnet F, Aurillac-Lavignolle V, Breilh D, et al; GESCA. Pravastatin in HIV-infected patients treated with protease inhibitors: a placebo-controlled randomized study. HIV Clin Trials. 2007;8:53-60. doi: 10.1310/hct0801-53
  34. Smith MEB, Lee NJ, Haney E, Carson S. Drug Class Review: HMG-CoA reductase inhibitors (statins) and fixed-dose combination products containing a statin: final report update 5. Portland, OR: Oregon Health & Science University; 2009.
  35. Balt CA. Hypertension and HIV infection. J Assoc Nurses AIDS Care. 2013;24:S127-S134. doi: 10.1016/j.jana.2012.06.012
  36. European AIDS Clinical Society. EACS Guidelines Version 8.1, October 2016. Accessed February 3, 2017.