Skip to main content
SpringerLink
Log in

Morphological and Metabolic Components of Lipodystrophy in Various Nevirapine-Based Highly Active Antiretroviral Therapy (HAART) Regimens

A Cross-Sectional, Observational Study

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background: Morphological abnormalities (lipoatrophy and central fat accumulation) and metabolic changes (dyslipidaemia and glucose regulation impairment) have emerged as components of lipodystrophy and as major tolerability issues with long-term use of highly active antiretroviral therapy (HAART) in HIV-positive patients. Protease inhibitors (PIs) are recognized as having the greatest impact in terms of metabolic complications, followed by nucleoside reverse transcriptase inhibitors, while the non-nucleoside reverse transcriptase inhibitors (NNRTIs) have the least impact. In particular, regimens based on the NNRTI nevirapine have been shown to achieve significant metabolic benefits and may help to improve dyslipidaemia. Improvements in body shape changes associated with lipodystrophy have also been reported when nevirapine replaced a PI in long-term triple therapy.

Objective: The objective of this cross-sectional observational (‘real-world’) study was to investigate the effect of three HAART regimens plus stable nevirapine therapy on morphological and metabolic components of lipodystrophy in HIV-infected patients.

Methods: Consecutive patients (aged >18 years) with serologically documented HIV infection, who had received HAART for at least 2 years and who had been diagnosed with lipodystrophy, were followed up as outpatients at the metabolic clinic of the University of Modena and Reggio Emilia, Modena, Italy. Patients received stable nevirapine therapy plus fixed-dose combinations of tenofovir disoproxil fumarate plus emtricitabine (Truvada®; TVD), zidovudine plus lamivudine (3TC) [Combivir®; CBV], or abacavir plus lamivudine (Kivexa®; KVX). Multivariate regression analyses were performed to analyse predictors of four components of lipodystrophy: lipoatrophy using leg fat mass measured by dual-emission x-ray absorptiometry (DXA), fat accumulation using waist circumference, dyslipidaemia using apolipoprotein (Apo)B/ApoA1 ratio, and glucose intolerance using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR).

Results: Overall, 101 patients were enrolled (TVD group = 61, CBV group = 20, KVX group = 20); 191 observations were analysed. Male sex was associated with reduced leg fat mass, while age and body mass index (BMI) were associated with increased leg fat mass (all p<0.05). Leg fat mass and male sex were associated with increased waist circumference (p < 0.001 for both). Leg fat mass predicted reduced ApoB/ApoA1 ratio, while age and BMI predicted increased ApoB/ApoA1 ratio (all p<0.05). BMI predicted HOMA-IR increase (p = 0.0017). No differences in lipoatrophy, central fat accumulation, dyslipidaemia or glucose metabolism were observed among any of the three different nevirapine plus nucleoside backbone groups (TVD, CBV or KVX).

Conclusion: HAART including nevirapine has a limited impact on components of lipodystrophy in patients with HIV infection. Further studies are needed to verify if nevirapine overcomes the expected distinct lipodystrophy risk profile associated with different nucleoside backbone therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Table II

Similar content being viewed by others

References

  1. Fisac C, Fumero E, Crespo M, et al. Metabolic benefits 24 months after replacing a protease inhibitor with abacavir, efavirenz or nevirapine. AIDS 2005; 19: 917–25

    Article  PubMed  CAS  Google Scholar 

  2. Fisac C, Virgili N, Ferrer E, et al. A comparison of the effects of nevirapine and nelfinavir on metabolism and body habitus in antiretroviral-naive human immunodeficiency virus-infected patients: a randomized controlled study. J Clin Endocrinol Metab 2003; 88: 5186–92

    Article  PubMed  CAS  Google Scholar 

  3. van Vonderen MG, van Agtmael MA, Hassink EA, et al. Zidovudine/lamivudine for HIV-1 infection contributes to limb fat loss. PLoS One 2009; 4: e5647

    Article  PubMed  Google Scholar 

  4. DHSS. 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; 2008 Nov 3: 1–139

  5. EACS. European AIDS Clinical Society (EACS) guidelines 2008. Guidelines for the clinical management and treatment of HIV infected adults in Europe. Version 4: Paris, October 2008

  6. Bonjoch A, Paredes R, Domingo P, et al. Long-term safety and efficacy of nevirapine-based approaches in HIV type 1-infected patients. AIDS Res Hum Retroviruses 2006; 22: 321–9

    Article  PubMed  CAS  Google Scholar 

  7. Milinkovic A, Martinez E. Nevirapine in the treatment of HIV. Expert Rev Anti Infect Ther 2004; 2: 367–73

    Article  PubMed  CAS  Google Scholar 

  8. Reliquet V, Allavena C, Francois-Brunet C, et al. Long-term assessment of nevirapine-containing highly active antiretroviral therapy in antiretroviral-naive HIV-infected patients: 3-year follow-up of the VIRGO study. HIV Med 2006; 7: 431–6

    Article  PubMed  CAS  Google Scholar 

  9. Ribera E, Rodriguez-Pardo D, Rubio M, et al. Efficacy and safety of once-daily combination therapy with didanosine, lamivudine and nevirapine in antiretroviral-naive HIV-infected patients. Antivir Ther 2005; 10: 605–14

    PubMed  CAS  Google Scholar 

  10. Hammer SM, Eron Jr JJ, Reiss P, et al. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society—USA Panel. JAMA 2008; 300: 555–70

    Article  PubMed  CAS  Google Scholar 

  11. Bergersen BM. Cardiovascular risk in patients with HIV Infection: impact of antiretroviral therapy. Drugs 2006; 66: 1971–87

    Article  PubMed  Google Scholar 

  12. Clotet B, van der Valk M, Negredo E, et al. Impact of nevirapine on lipid metabolism. J Acquir Immune Defic Syndr 2003; 34Suppl. 1: S79–84

    Article  PubMed  CAS  Google Scholar 

  13. Gazzard BG. British HIV Association guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008. HIV Medicine 2008; 9: 563–608

    Article  PubMed  CAS  Google Scholar 

  14. Barreiro P, Soriano V, Blanco F, et al. Risks and benefits of replacing protease inhibitors by nevirapine in HIV-infected subjects under long-term successful triple combination therapy. AIDS 2000; 14: 807–12

    Article  PubMed  CAS  Google Scholar 

  15. Guaraldi G, Orlando G, Squillace N, et al. Multidisciplinary approach to the treatment of metabolic and morphologic alterations of HIV-related lipodystrophy. HIV Clin Trials 2006; 7: 97–106

    Article  PubMed  Google Scholar 

  16. Schmidt C, Fagerberg B, Wikstrand J, et al. ApoB/apoA-I ratio is related to femoral artery plaques and is predictive for future cardiovascular events in healthy men. Atherosclerosis 2006; 189: 178–85

    Article  PubMed  CAS  Google Scholar 

  17. Lee S, Choi S, Kim HJ, et al. Cutoff values of surrogate measures of insulin resistance for metabolic syndrome in Korean non-diabetic adults. J Korean Med Sci 2006; 21: 695–700

    Article  PubMed  Google Scholar 

  18. Grundy SM, Balady GJ, Criqui MH, et al. Primary prevention of coronary heart disease: guidance from Framingham. A statement for healthcare professionals from the AHA Task Force on Risk Reduction. Circulation 1998; 97: 1876–87

    Article  PubMed  CAS  Google Scholar 

  19. Grundy SH, D’Agostino RB, Mosca L, et al. Summary of National Heart, Lung, and Blood Institute workshop on cardiovascular risk assessment. National Heart, Lung, and Blood Institute, Bethesda, MD, 2003

  20. Barbaro G, Iacobellis G. Metabolic syndrome associated with HIV and highly active antiretroviral therapy. Curr Diab Rep 2009; 9: 37–42

    Article  PubMed  CAS  Google Scholar 

  21. Guaraldi G, Stentarelli C, Zona S, et al. Lipodystrophy and anti-retroviral therapy as predictors of sub-clinical atherosclerosis in human immunodeficiency virus infected subjects. Atherosclerosis 2010; 208: 222–7

    Article  PubMed  CAS  Google Scholar 

  22. Petit JM, Duong M, Masson D, et al. Serum adiponectin and metabolic parameters in HIV-1-infected patients after substitution of nevirapine for protease inhibitors. Eur J Clin Invest 2004; 34: 569–75

    Article  PubMed  CAS  Google Scholar 

  23. Calza L, Manfredi R, Colangeli V, et al. Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy for the management of dyslipidaemia. AIDS 2005; 19: 1051–8

    Article  PubMed  CAS  Google Scholar 

  24. Negredo E, Ribalta J, Paredes R, et al. Reversal of atherogenic lipoprotein profile in HIV-1 infected patients with lipodystrophy after replacing protease inhibitors by nevirapine. AIDS 2002; 16: 1383–9

    Article  PubMed  CAS  Google Scholar 

  25. van der Valk M, Kastelein JJ, Murphy RL, et al. Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile. AIDS 2001; 15: 2407–14

    Article  PubMed  Google Scholar 

  26. Young J, Weber R, Rickenbach M, et al. Lipid profiles for antiretroviral-naive patients starting PI- and NNRTI-based therapy in the Swiss HIV cohort study. Antivir Ther 2005; 10: 585–91

    PubMed  CAS  Google Scholar 

  27. Manfredi R, Calza L, Chiodo F. An extremely different dysmetabolic profile between the two available non-nucleoside reverse transcriptase inhibitors: efavirenz and nevirapine. J Acquir Immune Defic Syndr 2005; 38: 236–8

    Article  PubMed  Google Scholar 

  28. van der Valk M, Reiss P. Lipid profiles associated with antiretroviral drug choices. Curr Opin Infect Dis 2003; 16: 19–23

    Article  PubMed  Google Scholar 

  29. Martinez E, Conget I, Lozano L, et al. Reversion of metabolic abnormalities after switching from HIV-1 protease inhibitors to nevirapine. AIDS 1999; 13: 805–10

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Giovanni Guaraldi has acted as a consultant to and/or received honoraria from Contura, Gilead Sciences, ViiV Healthcare, Merck and Boehringer Ingelheim, and has received research funding from Gilead Sciences, Bristol-Myers Squibb, Merck, Theratecnologies and ViiV Healthcare. All of the other authors declare no conflicts of interest. Medical writing support was provided by Susan Keam and Claire Byrne of InScience Communications, a Wolters Kluwer business, and funded by an unrestricted grant from Boehringer Ingelheim, Italy.

Author information

Authors and Affiliations

  1. Department of Medicine and Medicine Specialities, Infectious Diseases Clinic, University of Modena and Reggio Emilia School of Medicine, Via del Pozzo 71, 41100, Modena, Italy

    Giovanni Guaraldi MD, Stefano Zona, Gabriella Orlando, Federica Carli, Chiara Stentarelli, Kety Luzi, Elisa Garlassi, Marianna Menozzi & Pietro Bagni

  2. Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, Segrate, Milan, Italy

    Fulvio Adorni

Authors
  1. Giovanni Guaraldi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stefano Zona
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabriella Orlando
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Federica Carli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chiara Stentarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kety Luzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elisa Garlassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marianna Menozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pietro Bagni
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Fulvio Adorni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovanni Guaraldi MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guaraldi, G., Zona, S., Orlando, G. et al. Morphological and Metabolic Components of Lipodystrophy in Various Nevirapine-Based Highly Active Antiretroviral Therapy (HAART) Regimens. Clin. Drug Investig. 31, 759–767 (2011). https://doi.org/10.1007/BF03256916

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03256916

Keywords

Search

Navigation