HIV and dyslipidaemia

Human immunodeficiency virus (HIV) is a chronic disease associated with increased mortality and morbidity from HIV-related conditions. Also patients with HIV have an increased cardiovascular risk which is related to a HIV-induced dyslipidaemia as well as concerns about dyslipidaemia associated with some antiretroviral therapies used in this disease (1,2,3)

• HIV is associated with dyslipidemia in the form of high triglycerides and low high-density lipoprotein (HDL)
  
  
  • possible mechanisms for HIV-induced dyslipidaemia are increased cytokine levels (TNF and IL-6), decreased lipid clearance, and increased hepatic synthesis of very low-density lipoprotein (VLDL)
    
    
• HIV represents a chronic inflammatory condition, and this may lead to insulin resistance (3,4,5)
  
  
  
  
  • changes in body configuration (central obesity, truncal obesity, and lipoatrophy) and associated dyslipidaemia all accelerate the process that lead to diabetes mellitus with HIV and cART (combination antiretrovial therapy) (4,5)
    
    
    • HIV-associated lipodystrophy syndrome consists of lipoatrophy, lipohypertrophy, and metabolic disturbances (dyslipidemia and hyperglycaemia)
      • lipoatrophy involves the face, lower limbs, and buttocks
        • closely related to nucleoside reverse-transcriptase inhibitors (NRTIs) and rarely associated with protease inhibitors (PIs)
      • lipohypertrophy is related to the accumulation of adipose tissue (abdomen, breast, and interscapular fat), and this is likely due to PIs
        • central fat accumulation is observed more in females
        • associated with increased body fat
          
          
      • PIs are also associated with dyslipidaemia due to mitochondrial toxicity and inhibition of glucose transporter type 4
        • results in inhibition of adipocyte differentiation and an increase in triglyceride levels and insulin resistance
      • NRTIs can also be associated with dyslipidemia and insulin resistance
        
        
      • other mechanisms were suggested to contribute towards development of HIV-associated lipodystrophy syndrome
        • some examples include inflammation, inhibition of lipid metabolism (inhibition of lipoprotein lipase and excess triglyceride and risk of insulin resistance), oxidative stress and impaired function of adipokines and transcript factors (adiponectin, leptin, sterol regulatory binding proteins (SREBPs) and peroxisomal proliferatory activator receptors (PPAR) alpha and gamma
• it has been suggested that there is an independent HIV effect on cardiovascular risk (3,5)
  • NICE suggest that "people treated for HIV" should be considered at increased cardiovascular risk (6)
    
    
  • administration of combination antiretroviral therapy (cART) is associated with an increase in the incidence of metabolic risk factors (insulin resistance, lipoatrophy, dyslipidemia, and abnormalities of fat distribution) in HIV patients (1,2,4.5,7)
    • a multicenter cross-sectional study of elderly individuals with HIV, dyslipidaemia found in 54%, cardiovascular disease (CVD) in 23%, and lipodystrophy in 58% (8)
    • Hejazi et al found that dyslipidaemia is common in HIV subjects receiving antiretroviral medication: it reaches (82.3%) among 1,583 patients in their Malaysian study (9)

Reference:

• 1) Bittar R, Giral P, Aslangul E, et al. Determinants of low-density lipo - protein particle diameter during antiretroviral therapy including protease inhibitors in HIV-1-infected patients. Antivir Ther . 2012;17(5): 855-860.
• 2) Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalities in HIV-infected adults. N Engl J Med . 2005;352(1):48-62.
• 3) Lo J, Grinspoon S. Cardiovascular disease in HIV-infected patients: does HIV infection in and of itself increase cardiovascular risk? Curr Opin HIV AIDS . 2008;3(3):207-213.
• 4) de Waal R, Cohen K, Maartens G. Systematic review of antiretroviral-associated lipodystrophy: lipoatrophy, but not central fat gain, is an antiretroviral adverse drug reaction. PLoS One. 2013;8(5):e63623.
• 5) Kotler DP. HIV lipodystrophy etiology and pathogenesis. Body composition and metabolic alterations: etiology and pathogenesis. AIDS Read. 2003;13(Suppl 4):S5-S9.
• 6) NICE (2016). Cardiovascular disease: risk assessment and reduction, including lipid modification,
• 7) Dubé MP, Parker RA, Tebas P, et al. Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to nelfinavir or efavirenz plus dual nucleosides. AIDS 2005;19(16): 1807-1818.
• 8) Mothe B, Perez I, Domingo P, et al. HIV-1 infection in subjects older than 70: a multicenter cross-sectional assessment in Catalonia, Spain. Curr HIV Res . 2009;7(6):597-600.
• 9) Hejazi N, Rajikan R, Choong CL, Sahar S. Metabolic abnormalities in adult HIV infected population on antiretroviral medication in Malaysia: a cross-sectional survey. BMC Public Health . 2013;13:758.