Increased Risk of Lipoatrophy Under Stavudine

Abstract and Introduction

Objectives: To compare the incidence of clinical lipodystrophy in HIV-1-infected patients receiving zidovudine or stavudine, in combination with indinavir and lamivudine, in a randomized trial.
Methods: NOVAVIR was a randomized multicentre trial comparing stavudine/lamivudine/indinavir and zidovudine/lamivudine/indinavir in 170 patients pretreated with zidovudine, didanosine or zalcitabine (> 6 months), but naive for lamivudine, stavudine and protease inhibitors. The incidence of clinical lipodystrophy and metabolic abnormalities was assessed in a subgroup of 101 patients after 30 months of follow-up.
Results: The incidence of lipoatrophy was increased in the stavudine arm versus the zidovudine arm, as followed: facial atrophy: 48 versus 22% of patients, P = 0.011, lower limb atrophy: 49 versus 22% of patients, P = 0.006, buttock atrophy: 47 versus 20% of patients, P = 0.009, venomegaly: 57 versus 24% of patients, P = 0.001. There was no significant difference in the incidence of clinical signs of central fat accumulation nor in fasting metabolic parameters at month 30 between the two arms. In multivariate analyses, the stavudine arm, previous therapy with didanosine, and a lower CD4 cell count at study entry were associated with an increased risk of lipoatrophy, whereas older patients and women had an increased risk of lipohypertrophy.
Conclusion: Patients receiving stavudine/lamivudine/indinavir had a greater rate of clinical lipodystrophy, mainly lipoatrophy, than those treated with zidovudine/lamivudine/indinavir.

Highly active antiretroviral therapy (HAART) for HIV-1 therapy has decreased AIDS-related mortality.^[1,2] However, coincident with these advances, was described a lipodystrophy syndrome occurring in HIV-infected individuals receiving HAART.^[3] This syndrome is characterized by body fat redistribution loading to peripheral fat wasting and central adiposity. Metabolic abnormalities have also been reported, such as elevated triglyceride and cholesterol levels, and insulin resistance or type 2 diabetes mellitus. It is still unclear whether morphological changes and metabolic abnormalities are related or if they represent several distinct conditions.

The prevalence of lipodystrophy varies widely, because of the lack of a consistent definition, variability in diagnostic techniques, and various durations of follow-up. It ranges from 5 to 83% in patients receiving a protease inhibitor (PI).^[3,4] Although the initial identification of this syndrome was coincident with the widespread use of PI-containing regimens, more recent reports have concluded that it may occur in the absence of PI,^[5,6] and the aetiology of this syndrome remains unclear. The clinical changes, particularly lipoatrophy, have a major psychological impact that may alter the desire to continue antiretroviral therapy.

In both PI-sparing or in PI-containing regimens, the role of nucleoside reverse transcriptase inhibitors (NRTI) in the occurrence of lipodystrophy has been studied in retrospective, non-randomized studies. Stavudine was shown in different studies to be associated with a higher relative risk for the development of lipodystrophy (primarily fat loss).^[4,7,8,9] Few randomized studies have evaluated the role of NRTI in lipoatrophy.^[10,11,12]

NOVAVIR is a randomized multicentre trial comparing the activity and toxicity of lamivudine and indinavir, in combination with zidovudine or stavudine, in patients previously exposed to zidovudine, didanosine or zalcitabine, but naive for stavudine, lamivudine and PI. Antiviral activity and toxicity were similar in both arms after 18 months follow-up.^[13] The incidence of clinical lipodystrophy and metabolic abnormalities was assessed in a subgroup of patients after 30 months of follow-up. As the two arms differed only by the NRTI, zidovudine or stavudine, associated with lamivudine and indinavir, this trial gives the opportunity to assess the influence of stavudine versus zidovudine on the occurrence of lipodystrophy in a randomized trial.

AIDS. 2002;16(18) © 2002 Lippincott Williams & Wilkins
Lippincott Williams & Wilkins

Cite this: Increased Risk of Lipoatrophy Under Stavudine in HIV-1-Infected Patients: Results of a Substudy from a Comparative Trial - Medscape - Dec 01, 2002.

Sidebar: Appendix - NOVAVIR Study Organization

Scientific Committee: J.-P. Aboulker, B. Bazin, F. Brun-Vézinet, I. Carrière, A. Certain, J. Dormont, Y. Esnault, P. Flandre, P.-M. Girard, V. Joly, C. Katlama, V. Meiffrédy, C. Michelet, J.-M. Molina, A. Prieur, F. Raffi, D. Séréni, P. Yeni.

Participating Clinical Centres: Centre Hospitalier de Belfort, Belfort (J.-P. Faller, P. Elinger); Centre Hospitalier La Milétrie, Poitiers (J.-P. Breux, M. Duballet); CHRU Pointe à Pitre-Abymes, Guadeloupe (B. Contamin, M. Strobel); Hôpital Robert Debré, Reims (I. Beguinot, G. Remy); Hôpital Corvisart, Charleville Mézières (M. Bouvier-Alias, P. Lanoux, C. Penalba); Hôpital Avicenne, Bobigny (B. Jarrousse, P. Honoré); Hôpital Saint-Jacques, Besançon (G. Achard, C. Drobacheff, H. Gil, B. Hoen, C. Roche); Hôpital André Mignot, Le Chesnay (J. Doll); Hôpital Cochin, Paris (J. Krulik, D. Sicard, D. Séréni, B. Silbermann); Hôpital Bicêtre, Le Kremlin Bicêtre (J.-F. Delfraissy, C. Goujard, M. Mole, M.-T. Rannou); Hôpital Lariboisière, Paris (J.-M. Salord, V. Vincent, M. Parrinello); Hôpital Henri Duffaut, Avignon (G. Brun, G. Lepeu); Hôpital Jean Verdier, Bondy (V. Jeantils, C. Thaleb); Hôpital Rothschild, Paris (N. Adda, T. Nguyen, W. Rozenbaum); Hôpital Antoine Béclère, Clamart (F. Boue, V. Chambrin, G. Lubart); (Hôpital Bichat Claude-Bernard, Paris (Y. Bennai, L. Belardi, E. Bouvet, I. Fournier, C. Gaudebout, V.Joly, C. Mandet, S. Masson, P. Yeni); Centre Médico-Chirurgical Foch, Suresnes (I. Vergne, D. Zucmann); Hôpital Henri Mondor, Créteil (M. Lechevallier, A. Sobel); Hôpital Pitié-Salpétrière, Paris (C. Katlama, S. Maury, H. Schoen); Hôpital Saint-Louis, Paris (J. Modaï, M.-N. Sombardier); Hôpital Pierre Zobda-Quitman, Fort de France (A. Cabie, V. Beaujolais, G. Sobesky); Hôpital d'Angers, Angers (J.-M. Chennebault, P. Fialaire, E. Vivien); CHR Pellegrin, Bordeaux (T. Galperine, J.-M. Ragnaud); Hôpital Saint-André, Bordeaux (M. Bonarek, Ph. Morlat); Hôpital Hôtel Dieu, Lyon (C. Carré, L. Cotte, C. Trépo); Hôpital Sainte Marguerite, Marseille (T. Dinh, G. Fabre, J.-A. Gastaut); CHU Gui de Chauliac, Montpellier (C. Merle, J. Reynes, M. Vidal); Hôpital Hôtel Dieu, Nantes (M.-F. Charonnat, A. Huart, F. Raffi, M. Sicot); Hôpital De L'Archet, Nice (Ph. Clevenbergh, P. Dellamonica); Hôpital Pontchaillou, Rennes (C. Arvieux, F. Cartier, F. Souala); Centre Hospitalier La Beauchée, Saint Brieuc (C. Devaurs, C. Hascoet); CHRU de Strasbourg, Strasbourg (V. Krantz, J.-M. Lang); Hôpital de Purpan, Toulouse (M.-F. Garbay, P. Massip); CHU Côte de Nacre, Caen (C. Bazin, P. Goubin, M. Six); Hôpital de Tourcoing, Tourcoing (Y. Mouton); Hôpital de Brabois, Vandoeuvre les Nancy (C. Burty, Ph. Canton, Th. May); Hôpital Charles Nicolle, Rouen (F. Borsa-Lebas, Y. Debab); Centre Hospitalier de Compiègne, Compiègne (L. Geffray, D. Merrien).

Data and Safety Monitoring Board: E. Hirsch, J. Puel, M. Seligmann, M. Vray.

Coordinating Trial Centre: INSERM SC10: J.-P. Aboulker, B. Bazin, P. Flandre, M. Harel, S. Hazebrouck, N. Leturque, V. Meiffrédy, A. Prieur, Y. Saïdi. ARCAM: R. Léonard, A. Dauphin, R. Laillier.

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

My Alerts