A PHP Error was encountered

Severity: 8192

Message: Non-static method Low_search_model::load_models() should not be called statically, assuming $this from incompatible context

Filename: low_search/base.low_search.php

Line Number: 279

A PHP Error was encountered

Severity: 8192

Message: Non-static method Low_title::usage() should not be called statically, assuming $this from incompatible context

Filename: low_title/pi.low_title.php

Line Number: 9

Dyslipidemia – Causes

Causes

The exact mechanism by which HIV and ARV therapy cause dyslipidemia has not been determined,1 although a number of mechanisms have been proposed.


Dyslipidemia due to HIV infection

Substantial changes in lipid levels have been observed in HIV-positive patients.2

  • Significantly lower levels of total cholesterol, high-density lipoprotein cholesterol (HDL-c)3,4 and low-density lipoprotein cholesterol (LDL-c)4, and raised serum triglyceride concentrations5 have been observed in HIV-positive patients compared with HIV seronegative controls.

Summary of HIV treatment-associated dyslipidemia

  • The use of protease inhibitors (PIs) has been associated with hyperlipidemia.6–8
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are associated with increases in HDL-c.9
  • Nucleoside reverse transcriptase inhibitors (NRTIs) are heterogeneous in their lipid effects, which may depend on interactions with other ARV drugs in the regimen.1

Relative dyslipidemia effects of ARV therapy:

PIs

  • All ritonavir-boosted PIs increase HDL-c, LDL-c, and triglyceride levels.10
  • Lopinavir/ritonavir and fosamprenavir/ritonavir increase triglyceride levels to a greater extent than darunavir/ritonavir and atazanavir/ritonavir.10
  • Nelfinavir has been associated with a reduced risk of lower HDL-c levels compared with other PIs.11
  • Saquinavir has been associated with a lower total cholesterol:HDL-c ratio compared with other PIs.11

NNRTIs

  • Efavirenz has been associated with higher levels of total cholesterol and triglycerides compared with nevirapine.11 
  • No significant differences between efavirenz and nevirapine with regard to either HDL-c levels or total cholesterol:HDL-c ratios have been reported.11 
  • Few data are available on the dyslipidemic effects of etravirine. In the summary of product characteristics document for etravirine, dyslipidemia is currently listed as an uncommon adverse event; however, lipid disorders (e.g. hypercholesterolemia, hypertriglyceridemia, and hyperlipidemia) are listed as common adverse events.12

NRTIs

  • In recent guidelines issued by the US Department of Health and Human Services, increased levels of LDL-c and triglycerides were noted, in order of severity, following treatment with stavudine, zidovudine, and abacavir.10
  • Substitution of stavudine with tenofovir has been associated with a sustained improvement in dyslipidemia and a significant decrease in cardiovascular risk.13
  • The observational cohort study D:A:D has shown that patients receiving didanosine, stavudine, lamivudine or abacavir experienced some level of dyslipidemia. Fewer patients treated with zidovudine experienced dyslipidemia compared with the other treatments tested.14


Entry inhibitors

  • There is no evidence that enfuvirtide11 or maraviroc15 contribute to substantial alteration of lipid metabolism. Maraviroc may even have some favorable effects on lipid profiles in dyslipidemic patients.15 Ongoing studies will continue to investigate the metabolic profile of maraviroc. 


Integrase Inhibitors

  • Few data are available on the dyslipidemic effects of raltegravir. Few data are available to determine whether raltegravir would cause similar lipid dysregulation to other ARV treatments. In the summary of product characteristics document for raltegravir, dyslipidemia is currently listed as an uncommon adverse event.16 

Prevalence of dyslipidemia in patients enrolled in the observational cohort D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) study11




Dyslipidemia is defined as total cholesterol level: ≥6.2 mmol/L (≥240 mg/dL), HDL-c: ≤0.9 mmol/L (≤35 mg/dL), LDL-c: ≥4.1 mmol/L (≥159 mg/dL), TC:HDL-c ratio: ≥6.5, or triglyceride level: ≥2.3 mmol/L.*

Adapted with permission from Oxford Journals.
*2.3 mmol/L = 204 mg/dL




Refer to the risk factors section for information on potential exacerbating conditions.
 

References

  1. Tungsiripat M, Aberg JA. Dyslipidemia in HIV patients. Cleve Clin J Med. 2005;72:1113–1120.
  2. Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA. 2003;289:2978–2982.
  3. Grunfeld C, Pang M, Doerrler W, et al. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992;74:1045–1052.
  4. Shor-Posner G, Basit A, Lu Y, et al. Hypocholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection. Am J Med. 1993;94:515–519.
  5. Hellerstein MK, Grunfeld C, Wu K, et al. Increased de novo hepatic lipogenesis in human immunodeficiency virus infection. J Clin Endocrinol Metab. 1993;76:559–565.
  6. Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998;12:F51–58.
  7. Périard D, Telenti A, Sudre P, et al. Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. The Swiss HIV Cohort Study. Circulation. 1999;100:700–705.
  8. Mulligan K, Grunfeld C, Tai VW, et al. Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. J Acquir Immune Defic Syndr. 2000;23:35–43.
  9. Dubé MP, Stein JH, Aberg JA, et al. Guidelines for the Evaluation and Management of Dyslipidemia in Human Immunodeficiency Virus (HIV)–Infected Adults Receiving Antiretroviral Therapy: Recommendations of the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. Clin Infect Dis. 2003;37:613–627.
  10. 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. 2011;1–166. Accessed 5 August 2011.
  11. Fontas E, van Leth F, Sabin CA, et al. Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J Infect Dis. 2004;189:1056–1074.
  12. European Medicines Agency. Etravirine Summary of Product Characteristics. Accessed 7 October 2011.
  13. Llibre JM, Domingo P, Palacios R, et al. Sustained improvement of dyslipidemia in HAART-treated patients replacing stavudine with tenofovir. AIDS. 2006;26;20(10):1407-1414.
  14. D:A:D Study Group. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. 2008;26;371(9622):1417-1426.
  15. MacInnes A, Lazzarin A, Di Perri G, et al. Maraviroc can improve lipid profiles in dyslipidemic patients with HIV: results from the MERIT trial. HIV Clin Trials. 2011;12(1):24-36.
  16. European Medicines Agency. Raltegravir Summary of Product Characteristics. Accessed 4 October 2011.