Blood lipid changes at long-term antiretroviral treatment

Česká verzia

Authors: S. Snopková ¹; J. Jarkovský ² ; M. Matýšková ³; K. Povolná ¹; P. Polák ¹; M. Cvanová ²; P. Husa ¹
Authors place of work: Klinika infekčních chorob Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Petr Husa, CSc. ¹; Institut biostatistiky a analýz Lékařské a Přírodovědecké fakulty MU Brno, ředitel doc. RNDr. Ladislav Dušek, Ph. D. ²; Oddělení klinické hematologie FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Miroslav Penka, CSc. ³
Published in the journal: Vnitř Lék 2011; 57(5): 463-471
Category: Original Contributions

Summary

The aim of study was to find the development trend of blood lipid concentration in a group of HIV positive patients treated by combination antiretroviral therapy (cART). We followed changes during the therapy and evaluated their aterogennic nature.

Methods:
The group included 118 patients stepwise allocated to the AIDS Centre of the Faculty Hospital Brno, with the monitoring period being up to 1 month as the minimum and up to 17 years as the maximum. The patients were divided into cART treated patients and not treated patients. The following parameters were analysed: total cholesterol, triglycerides, HDL-cholesterol, apolipoprotein B, the total cholesterol/HDL-cholesterol index and non-HDL-cholesterol.

Results:
Our group experienced a statistically significant increase of total cholesterol concentration already in the first months after cART initiation and this value continuously increased in the following years. The recommended target value for total cholesterol (5 mmol/ l) was exceeded in the group of patients after 3 – 4 years of cART initiation. The triglyceride concentration showed a sudden increase already a few months after cART initiation, when the recommended optimum value of triglycerides (1.7 mmol/ l) was exceeded. These changes had a further no statistic significance. The average triglyceride value was all around (slightly above) 1.7 mmol/ l. Our group experienced a statistically significant increase of HDL-cholesterol concentration in the first two years after cART initiation. A statistically significant change of HDL-cholesterol concentration was not found in the following years. The average HDL-cholesterol value was above optimal value HDL-Ch > 1.0 mmol/ l for men (except initial category). A statistically significant change of apolipoprotein B concentration was found after 3 – 4 years of cART treatment. However, the average apolipoprotein B value did not exceed the target value in any of the followed categories. No statistically significant changes of the total cholesterol/HDL-cholesterol index were found. The resulting value was under 5 in all the followed categories. Statistically significant changes of non-HDL-cholesterol were found in patients with cART already a few months after treatment initiation and its concentration continually increased. However, the recommended target value of non-HDL-cholesterol (3.8 mmol/ l) was exceeded only in the category of patients treated 4 – 5 years. The development trend of CD4⁺ lymphocyte count and HIV-1 RNA copies means high active of cART from standpoind of immunoregeneration (CD4⁺ lymphocyte count) and viral suppression (HIV-1 RNA copies) even in the group of treated patient with the longest monitoring period.

Conclusion:
Monitoring of our group of HIV-positive patients treated by combination antiretroviral therapy revealed a statistically significant increase of blood lipid concentrations (inclusive of HDL-cholesterol) during the treatment. However, these changes do not have an unequivocally aterogennic nature even in the group of treated patient with the longest monitoring period.

Key words:
HIV – combined antiretroviral therapy – total cholesterol – triglycerides – apolipoprotein B – index total cholesterol/HDL-cholesterol – non-HDL-cholesterol – CD4⁺ lymphocytes – HIV-1 RNA

Zdroje

1. Ranade K, Geese WJ, Noor M et al. Genetic analysis implicates resistin in HIV lipodystrophy. AIDS 2008; 22: 1561–1568.

2. Miller J, Carr A, Emery S et al. HIV lipodystrophy: prevalence, severity and correlates of risk in Australia. HIV Med 2003; 4: 293–301.

3. Martinez E, Visnegarwala F, Grund B et al. The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters. AIDS 2010; 24: 353–363.

4. Worm SW, Friis-Moller N, Bruyand M et al. High prevalence of the metabolic syndrome in HIV-infected patients: impact of different definitions of the metabolic syndrome. AIDS 2010; 24: 427–435.

5. Grinspoon SK Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus. Am J Med 2005; 118: (Suppl. 2): 23S–28S.

6. Grinspoon S, Carr A Cardiovascular risk and body fat abnormalities in HIV infected individuals. N Engl J Med 2005; 352: 48–62.

7. Satchell CS, Cotter AG, O´Connor EF et al. Platelet function and HIV: a case-control study. AIDS 2010; 24: 649–657.

8. Murphy R, Costagliola D Increased cardiovascular risk in HIV infection: drugs, virus and immunity. AIDS 2008; 22: 1625–1627.

9. Calza L, Manfredi R, Verucchi G Myocardial infarction risk in HIV-infected patients: epidemiology, pathogenesis, and clinical management. AIDS 2010; 24: 789–802.

10. Aslangul E, Assoumou L, Bittar R et al. Rosuvastatin versus pravastatin in dyslipidemic HIV-1-infected patients receiving protease inhibitors: a randomized trial. AIDS 2010; 24: 77–83.

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. Martinez E, Leyes P, Ros E. Effectiveness of lipid-lowering therapy in HIV patients. Curr Opin HIV AIDS 2008; 3: 240–246.

13. Chow D, Chen H, Glesby MJ et al. Short-term ezetimibe is well tolerated and effective in combination with statin therapy to treat elevated LDL cholesterol in HIV-infected patients. AIDS 2009; 23: 2133–2141.

14. Soška V. Stanovení LDL-cholesterolu – stále nevyřešený problém: vypočíst, nebo změřit? – editorial. Vnitř Lék 2008; 54: 943–944.

15. Soška V. Je dyslipidemie rizikovým faktorem pro nemocné léčené antiretrovirovými léky? – editorial. Vnitř Lék 2008; 54: 135–136.

16. Lemieux I, Lamarche B, Couillard C et al. Total cholesterol/HDL cholesterol ratio vs. LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study. Arch Intern Med 2001; 161: 2685–2692.

17. Philips AN, Carr A, Neuhaus J et al. Interruption of antiretroviral therapy and risk of cardiovascular disease in person with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther 2008; 13: 177–187.

18. Mangili A, Gerrior J, Tang AM et al. Risk of cardiovascular disease in a cohort of HIV-infected adults: a study using carotid intima-media thickness and coronary calcium score. Clin Infect Dis 2006; 43: 1482–1489.

19. Murphy R, Costagliola D. Increased cardiovascular risk in HIV infection: drugs, virus and immunity. AIDS 2008; 22: 1625–1627.

20. Kaplan RC, Kingsley LA, Gange SJ et al. Low CD4+ T-cell count as a major atherosclerosis risk factor in HIV-infected women and men. AIDS 2008; 22: 1615–1624.

21. Hirschel B, Flanigan T. Is it smart to continue to study treatment interruptions? AIDS 2009; 23: 757–759.

22. Van Leuven SI, Franssen R, Kastelein JJ et al. Systemic inflammation as a risk factor for atherothrombosis. Rheumatology 2008; 47: 3–7.

23. Maggiolo F, Airoldi M, Callegaro A et al. CD4 cell-guided scheduled treatment interruptions in HIV-infected patients with sustained immunologic response to HAART. AIDS 2009; 23: 799–807.

24. Calmy A, Gayet-Ageron A, Montecucco F et al on behalf of the STACCATO Study Group. HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS 2009; 23: 929–939.

25. The Writing Committee of the DAD Study Group. Cardio- and cerebrovascular events in HIV-infected persons. AIDS 2004; 13: 1811–1817.

26. Sankatsing R, Franssen R, Hassink E et al. Nevirapine increases high-density lipoprotein cholesterol concentration by stimulation of apolipoprotein A-I production. Arterioscler Tromb Vasc Biol 2009; 29: 1336–1341.

27. Phillips AN, Carr A, Neuhaus J et al. Interruption of antiretroviral therapy and risk of cardiovascular disease in person with HIV-1 infection: exploratory analyses from the SMART trial. Antivir Ther 2008; 13: 177–187.

28. Riddler SA, Xiuhong L, Otvos J et al. Antiretroviral Therapy Is Associated With an Atherogenic Lipoprotein Phenotype Among HIV-1 – Infected Man un th multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 2008; 48: 281–288.

29. Rosolová H. Snížení reziduálního vaskulárního rizika bude hlavní cíl preventivní kardiologie ve 21. století. Cor Vasa 2010; 52: 209–211.

30. Fruchart JC, Sacks FM, Hermans MP et al. Residual risk reduction initiative: výzva ke snížení reziduálního vaskulárního rizika u pacientů s dyslipidemií. Cor Vasa 2010; 52: 212–228.

31. Torre D, Pugliese A. Interleukin 18 and cardiovascular disease in HIV-1 infection: a partner in crime? AIDS Rev 2010; 12: 31–39.

32. Gallant J. Timing and Choice of First-Line Antiretroviral Therapy. 43–76. In: HIV/AIDS Annual Update 2009. Clinical care options HIV, Miami, 2009, 197.

33. Grunfeld C, Delanez A, Wanke Ch et al. Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study. AIDS 2009; 23: 1841–1849.

34. Lo J, Abbara S, Shturman L et al. Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS 2010; 24: 243–253.

35. Chaipan C, Soilleux E, Simpson P et al. DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets. J Virol 2006; 80: 8951–8960.

36. Madden E, Lee G, Kotler DP et al. Association of antiretroviral therapy with fibrinogen levels in HIV-infection. AIDS 2008; 22: 707–715.

37. The HIV-CAUSAL Collaboration. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. AIDS 2010; 24: 123–137.

38. Friis-Moller N, Sabin CA, Weber R et al. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003; 349: 1993–2003.