Lipodystrophy induced by combination antiretroviral therapy in HIV/AIDS patients: A Belgrade cohort study

  • Gordana Dragović Institute of Pharmacology, Clinical Pharmacology and Toxicology,Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Dragana Danilović Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Aleksandra Dimić Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Djordje Jevtović Institute of Infective and Tropical Diseases “Dr Kosta Todorovic”, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Keywords: lipodistrophy, incidence, risk factors, hiv, antiretroviral therapy, highly active, sex, hepatitis c,

Abstract


Background/Aim. Highly active antiretroviral therapy (HAART) has led to dramatic reductions in mortality and morbidity of HIV/AIDS-patients. Lipodystrophy, a syndrome including peripheral fat wasting and central obesity, is well-documented side effect of HAART. The aim of this study was to evaluate the incidence of lipodystrophy, and to determine its risk ratios in a HIV/AIDS-cohort. Methods. This cross-sectional study included all the antiretroviral-naive HIV/AIDS patients commencing HAART from October 1, 2001 to October 1, 2010, at the HIV/AIDS Center, Institute of Infectious and Tropical Diseases, Belgrade, Serbia. Univariate and stepwise multivariate logistic regression analyses were used to determine the odds ratios (OR) with the confidence interval (CI) of 95%, in order to establish the relative risk for lipodystrophy. The Kaplan-Meier-method was used to determine the probability of development lipodystrophy over time. All statistical analyses were performed using SPSS software version using 0.05 as a p-treshold for the significance. Results. This study included 840 HIV/AIDS patients, 608 women and 232 men, followed for 5.6 ± 2.8 years. The prevalence of lipodystrophy was 69.2%. Univariate and stepwise multivariate regression analysis identified that the female gender, hepatitis C coinfection, AIDS diagnosis prior to HAART initiation, nucleoside-reverse-transcriptase-inhibitors and protease-inhibitors based regimens had a high risk for developing lipodystrophy in HIV/AIDS-patients (OR = 1.6, 95% CI = 1.1–3.49, p = 0.04; OR = 3.31, 95% CI = 1.3–6.8, p < 0.01; OR = 3.7, 95% CI = 1.7–6.1, p < 0.01; OR = 2.1, 95% CI = 1.7–3.3, p < 0.01; OR = 6.1, 95% CI = 4.1–9.7, p < 0.01, respectively). Conclusion. Despite much greater life expectancy of HIV/AIDS-patients, treatment-related toxicities still remain a major concern. Monitoring of lipodystrophy, as side effect of HAART, is particularly important.

References

Palella FJ Jr, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, et al. HIV Outpatient Study Investigators. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr 2006; 43(1): 27−34.

Clumeck N, Pozniak A, Raffi F. European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of HIV-infected adults. HIV Med 2008; 9(2): 65−71.

Garg A. Acquired and inherited lipodystrophies. N Engl J Med 2004; 350(12): 1220−34.

Safrin S, Grunfeld C. Fat distribution and metabolic changes in patients with HIV infection. AIDS 1999; 13(18): 2493−505.

Carr A, Samaras K, Burton S, Law M, Freund J, Chisholm DJ, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998; 12(7): 51−8.

CDC. Revised classification system for HIV infection and ex-panded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992; 41(RR−17): 1−19.

Lundgren JD, Battegay M, Behrens G, De WS, Guaraldi G, Katlama C, et al. European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV. HIV Med 2008; 9(2): 72−81.

Miller J, Carr A, Emery S, Law M, Mallal S, Baker D, et al. . HIV lipodystrophy. Prevalence, severity and correlates of risk in Australia. HIV Med 2003; 4(3): 293−301.

Freitas P, Carvalho D, Santos AC, Madureira AJ, Xerinda S, Marti-nez E, et al. Central/Peripheral fat mass ratio is associated with increased risk of hypertension in HIV-infected patients. J Clin Hypertens (Greenwich) 2012; 14(9): 593−600.

Freitas P, Carvalho D, Santos AC, Mesquita J, Matos MJ, Madureira AJ, et al. Lipodystrophy defined by Fat Mass Ratio in HIV-infected patients is associated with a high prevalence of glu-cose disturbances and insulin resistance. BMC Infect Dis 2012; 12: 180.

Piloya T, Bakeera-Kitaka S, Kekitiinwa A, Kamya MR. Lipody-strophy among HIV-infected children and adolescents on highly active antiretroviral therapy in Uganda: a cross sectional study. J Int AIDS Soc 2012; 15(2): 17427.

Luetkemeyer AF, Havlir DV, Currier JS. Complications of HIV disease and antiretroviral therapy. Top Antivir Med 2012; 20(2): 48−60.

Domingo P, Estrada V, López-Aldeguer J, Villaroya F, Martínez E. Fat redistribution syndromes associated with HIV-1 infection and combination antiretroviral therapy. AIDS Rev 2012; 14(2): 112−23.

Singhania R, Kotler DP. Lipodystrophy in HIV patients: its chal-lenges and management approaches. HIV AIDS (Auckl) 2011; 3: 135−43.

Martinez E, Mocroft A, García-Viejo MA, Pérez-Cuevas JB, Blanco JL, Mallolas J, et al. Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study. Lancet 2001; 357(9256): 592−8.

Thiebaut R, Daucourt V, Mercie P, Ekouevi DK, Malvy D, Morlat P, et al. Lipodystrophy, metabolic disorders, and human immu-nodeficiency virus infection: Aquitaine Cohort, France, 1999. Clin Infect Dis 2000; 31(6): 1482−7.

Loko MA, Bani-Sadr F, Winnock M, Lacombe K, Carrieri P, Neau D, et al. Impact of HAART exposure and associated lipody-strophy on advanced liver fibrosis in HIV/HCV-coinfected patients. J Viral Hepat 2011; 18(7): e 307−14.

Laguno M, Milinkovic A, Lazzari E, Murillas J, Martínez E, Blanco JL, et al. Incidence and risk factors for mitochondrial toxicity in treated HIV/HCV-coinfected patients. Antivir Ther 2005; 10(3): 423−9.

Sulkowski MS, Benhamou Y. Therapeutic issues in HIV/HCV-coinfected patients. J Viral Hepat 2007; 14(6): 371−86.

McComsey G, Bai R, Maa J, Seekins D, Wong L. Extensive inves-tigations of mitochondrial DNA genome in treated HIV-infected subjects: beyond mitochondrial DNA depletion. J Acquir Immune Defic Syndr 2005; 39(2): 181−8.

Koczor CA, Lewis W. Nucleoside reverse transcriptase inhibitor toxicity and mitochondrial DNA. Expert Opin Drug Metab Toxicol 2010; 6(12): 1493−504.

Dragović GJ, Smith CJ, Jevtović DL, Johnson MA, Ranin J, Salemović D, et al. Comparison of nucleoside reverse transcriptase inhibitor use as part of first-line therapy in a Serbian and a UK HIV clinic. HIV Clin Trials 2009; 10(5): 306−13.

van Oosterhout JJ, Mallewa J, Kaunda S, Chagoma N, Njalale Y, Kampira E, et al. Stavudine toxicity in adult longer-term ART patients in Blantyre, Malawi. PLoS One 2012; 7(7): e42029.

Domingo P, Cabeza MC, Pruvost A, Salazar J, Gutierrez MD, Mateo MG, et al. Relationship between HIV/Highly active antiretro-viral therapy (HAART)-associated lipodystrophy syndrome and stavudine-triphosphate intracellular levels in patients with stavudine-based antiretroviral regimens. Clin Infect Dis 2010; 50(7): 1033−40.

Bussmann H, Wester WC, Thomas A, Novitsky V, Okezie R, Mu-zenda T, et al. Response to zidovudine/didanosine-containing combination antiretroviral therapy among HIV-1 subtype C-infected adults in Botswana: two-year outcomes from a ran-domized clinical trial. J Acquir Immune Defic Syndr 2009; 51(1): 37−46.

Lugassy DM, Farmer BM, Nelson LS. Metabolic and hepatobi-liary side effects of antiretroviral therapy (ART). Emerg Med Clin North Am 2010; 28(2): 409−19.

Potthoff A, Brockmeyer NH, Gelbrich G, Neuhaus K, Esser S, Reinsch N, et al. Lipodystrophy - a sign for metabolic syndrome in patients of the HIV-HEART study. J Dtsch Dermatol Ges 2010; 8(2): 92−8.

Ammassari A, Murri R, Pezzotti P, Trotta MP, Ravasio L, de Longis P, et al. Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection. J Acquir Immune Defic Syndr 2001; 28(5): 445−9.

Published
2015/04/23
Section
Original Paper