Switch to Efavirenz Attenuates Lipoatrophy in Girls With Perinatal HIV
Junwei Su
The Department of Infectious Diseases, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Search for more papers by this authorStephanie Shiau
Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ
Search for more papers by this authorStephen M. Arpadi
Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY
Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY
Search for more papers by this authorRenate Strehlau
Empilweni Services and Research Unit, Department of Pediatrics and Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa
Search for more papers by this authorMegan Burke
Empilweni Services and Research Unit, Department of Pediatrics and Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa
Search for more papers by this authorFaeezah Patel
Empilweni Services and Research Unit, Department of Pediatrics and Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa
Search for more papers by this authorLouise Kuhn
Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY
Search for more papers by this authorAshraf Coovadia
Empilweni Services and Research Unit, Department of Pediatrics and Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa
Search for more papers by this authorCorresponding Author
Michael T. Yin
Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY
Address correspondence and reprint requests to Michael T. Yin, MD, MS, Division of Infectious Diseases, Columbia University Irving Medical Center, 630W. 168th St, PH 8-876, New York, NY 10032 (e-mail: [email protected]).Search for more papers by this authorCHANGES Bone Study Team
Search for more papers by this authorJunwei Su
The Department of Infectious Diseases, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Search for more papers by this authorStephanie Shiau
Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ
Search for more papers by this authorStephen M. Arpadi
Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY
Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY
Search for more papers by this authorRenate Strehlau
Empilweni Services and Research Unit, Department of Pediatrics and Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa
Search for more papers by this authorMegan Burke
Empilweni Services and Research Unit, Department of Pediatrics and Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa
Search for more papers by this authorFaeezah Patel
Empilweni Services and Research Unit, Department of Pediatrics and Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa
Search for more papers by this authorLouise Kuhn
Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY
Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY
Search for more papers by this authorAshraf Coovadia
Empilweni Services and Research Unit, Department of Pediatrics and Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa
Search for more papers by this authorCorresponding Author
Michael T. Yin
Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY
Address correspondence and reprint requests to Michael T. Yin, MD, MS, Division of Infectious Diseases, Columbia University Irving Medical Center, 630W. 168th St, PH 8-876, New York, NY 10032 (e-mail: [email protected]).Search for more papers by this authorCHANGES Bone Study Team
Search for more papers by this authorSupplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 073977 and HD 073952).
The authors report no conflicts of interest.
ABSTRACT
Objectives:
Children with HIV (CHIV) have lifetime exposure to antiretrovirals (ART); therefore, optimizing their regimens to have the least impact on fat redistribution is a priority.
Methods:
This is a cross-sectional study of 219 perinatally infected CHIV and 219 HIV-uninfected controls from similar socioeconomic backgrounds in Johannesburg, South Africa. We compared total body and regional fat distribution in CHIV on suppressive ART regimens with controls and, among CHIV, between ritonavir-boosted lopinavir (LPV/r)-based and efavirenz (EFV)-based regimens.
Results:
The mean age of the 219 uninfected children (45% girls) and the 219 CHIV (48% girls) was 7.0 and 6.4 years, respectively. CHIV had lower adjusted total body fat (P = 0.005) and lower percentage fat at the trunk (P = 0.020), arms (P = 0.001), and legs (P < 0.001) than uninfected children. CHIV on LPV/r had similar body composition as those on EFV, except for arm fat mass (P = 0.030). When stratified by sex, girls with HIV on LPV/r had lower adjusted total (P = 0.007), trunk (P = 0.002), arms (P = 0.008), legs (P = 0.048) fat mass; trunk-to-total body fat (P = 0.044); and higher legs-to-total body fat (P = 0.011) than those on EFV.
Conclusions:
South African CHIV receiving ART had lower global and partial fat mass and percentage fat than healthy controls. In girls with HIV with sustained virologic suppression on ART, switching from LPV/r to EFV could attenuate fat mass loss, indicating that EFV-based regimen may be a better option in this group of individuals.
REFERENCES
- 1.Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS 1998; 12: F51–F58.
- 2.Green ML. Evaluation and management of dyslipidemia in patients with HIV infection. J Gen Intern Med 2002; 17: 797–810.
- 3.Innes S, Levin L, Cotton M. Lipodystrophy syndrome in HIV-infected children on HAART. South Afr J HIV Med 2009; 10: 76–80.
- 4.Daniels SR, Morrison JA, Sprecher DL, et al. Association of body fat distribution and cardiovascular risk factors in children and adolescents. Circulation 1999; 99: 541–545.
- 5.Rochira V, Guaraldi G. Growth hormone deficiency and human immunodeficiency virus. Best Pract Res Clin Endocrinol Metab 2017; 31: 91–111.
- 6.Arrive E, Viard JP, Salanave B, et al. Metabolic risk factors in young adults infected with HIV since childhood compared with the general population. PLoS One 2018; 13: e0206745.
- 7.Arpadi S, Shiau S, Strehlau R, et al. Metabolic abnormalities and body composition of HIV-infected children on Lopinavir or Nevirapine-based antiretroviral therapy. Arch Dis Child 2013; 98: 258–264.
- 8.Alam N, Cortina-Borja M, Goetghebuer T, et al. Body fat abnormality in HIV-infected children and adolescents living in Europe: prevalence and risk factors. J Acquir Immune Defic Syndr 2012; 59: 314–324.
- 9.Miller J, Carr A, Emery S, et al. HIV lipodystrophy: prevalence, severity and correlates of risk in Australia. HIV Med 2003; 4: 293–301.
- 10. European Paediatric Lipodystrophy Group. Antiretroviral therapy, fat redistribution and hyperlipidaemia in HIV-infected children in Europe. AIDS 2004; 18: 1443–1451.
- 11.Cohen S, Innes S, Geelen SP, et al. Long-term changes of subcutaneous fat mass in HIV-infected children on antiretroviral therapy: a retrospective analysis of longitudinal data from two pediatric HIV-cohorts. PLoS One 2015; 10: e0120927.
- 12.Arpadi SM, Bethel J, Horlick M, et al. Longitudinal changes in regional fat content in HIV-infected children and adolescents. AIDS 2009; 23: 1501–1509.
- 13.Bhagwat P, Ofotokun I, McComsey GA, et al. Changes in waist circumference in HIV-infected individuals initiating a raltegravir or protease inhibitor regimen: effects of sex and race. Open Forum Infect Dis 2018; 5: ofy201.
- 14.Coovadia A, Abrams EJ, Strehlau R, et al. Efavirenz-based antiretroviral therapy among nevirapine-exposed HIV-infected children in South Africa: a randomized clinical trial. JAMA 2015; 314: 1808–1817.
- 15.Murnane PM, Strehlau R, Shiau S, et al. Switching to efavirenz versus remaining on ritonavir-boosted lopinavir in human immunodeficiency virus-infected children exposed to nevirapine: long-term outcomes of a randomized trial. Clin Infect Dis 2017; 65: 477–485.
- 16.Arpadi SM, Shiau S, Strehlau R, et al. Efavirenz is associated with higher bone mass in South African children with HIV. AIDS 2016; 30: 2459–2467.
- 17.Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44: 291–303.
- 18.Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970; 45: 13–23.
- 19.Wong M, Shiau S, Yin MT, et al. Decreased vigorous physical activity in school-aged children with human immunodeficiency virus in Johannesburg, South Africa. J Pediatr 2016; 172: 103–109.
- 20.Wells JC, Cole TJ, Steam AS. Adjustment of fat-free mass and fat mass for height in children aged 8 y. Int J Obes Relat Metab Disord 2002; 26: 947–952.
- 21.Tshamala HK, Aketi L, Tshibassu PM, et al. The lipodystrophy syndrome in HIV-infected children under antiretroviral therapy: a first report from the Central Africa. Int J Pediatr 2019; 2019: 7013758.
- 22.Ellis KJ, Abrams SA, Wong WW. Monitoring childhood obesity: assessment of the weight/height index. Am J Epidemiol 1999; 150: 939–946.
- 23.Palella FJ Jr, Cole SR, Chmiel JS, et al. Anthropometrics and examiner-reported body habitus abnormalities in the multicenter AIDS cohort study. Clin Infect Dis 2004; 38: 903–907.
- 24.Shikuma CM, Gangcuangco LM, Killebrew DA, et al. The role of HIV and monocytes/macrophages in adipose tissue biology. J Acquir Immune Defic Syndr 2014; 65: 151–159.
- 25.Damouche A, Lazure T, Avettand-Fenoel V, et al. Adipose tissue is a neglected viral reservoir and an inflammatory site during chronic HIV and SIV infection. PLoS Pathog 2015; 11: e1005153.
- 26.Diaz-Delfin J, Domingo P, Wabitsch M, et al. HIV-1 Tat protein impairs adipogenesis and induces the expression and secretion of proinflammatory cytokines in human SGBS adipocytes. Antivir Ther 2012; 17: 529–540.
- 27.Shrivastav S, Kino T, Cunningham T, et al. Human immunodeficiency virus (HIV)-1 viral protein R suppresses transcriptional activity of peroxisome proliferator-activated receptor {gamma} and inhibits adipocyte differentiation: implications for HIV-associated lipodystrophy. Mol Endocrinol 2008; 22: 234–247.
- 28.Gallego-Escuredo JM, Del Mar Gutierrez M, Diaz-Delfin J, et al. Differential effects of efavirenz and lopinavir/ritonavir on human adipocyte differentiation, gene expression and release of adipokines and pro-inflammatory cytokines. Curr HIV Res 2010; 8: 545–553.
- 29.Capel E, Auclair M, Caron-Debarle M, et al. Effects of ritonavir-boosted darunavir, atazanavir and lopinavir on adipose functions and insulin sensitivity in murine and human adipocytes. Antivir Ther 2012; 17: 549–556.
- 30.El Hadri K, Glorian M, Monsempes C, et al. In vitro suppression of the lipogenic pathway by the nonnucleoside reverse transcriptase inhibitor efavirenz in 3T3 and human preadipocytes or adipocytes. J Biol Chem 2004; 279: 15130–15141.
- 31.Diaz-Delfin J, Del Mar Gutierrez M, Gallego-Escuredo JM, et al. Effects of nevirapine and efavirenz on human adipocyte differentiation, gene expression, and release of adipokines and cytokines. Antiviral Res 2011; 91: 112–119.
- 32.Gomez-Sucerquia LJ, Blas-Garcia A, Marti-Cabrera M, et al. Profile of stress and toxicity gene expression in human hepatic cells treated with Efavirenz. Antiviral Res 2012; 94: 232–241.
- 33.Blas-Garcia A, Apostolova N, Ballesteros D, et al. Inhibition of mitochondrial function by efavirenz increases lipid content in hepatic cells. Hepatology 2010; 52: 115–125.
- 34.Haubrich RH, Riddler SA, DiRienzo AG, et al. Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment. AIDS 2009; 23: 1109–1118.
- 35.Riddler SA, Haubrich R, DiRienzo AG, et al. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med 2008; 358: 2095–2106.
- 36.Domingo P, Gutierrez Mdel M, Gallego-Escuredo JM, et al. A 48-week study of fat molecular alterations in HIV naive patients starting tenofovir/emtricitabine with lopinavir/ritonavir or efavirenz. J Acquir Immune Defic Syndr 2014; 66: 457–465.
- 37.McComsey G, Bhumbra N, Ma JF, et al. Impact of protease inhibitor substitution with efavirenz in HIV-infected children: results of the First Pediatric Switch Study. Pediatrics 2003; 111: e275–e281.
- 38.Sharma TS, Somarriba G, Arheart KL, et al. Longitudinal changes in body composition by dual energy X-ray absorptiometry among perinatally HIV-infected and HIV-uninfected youth: increased risk of adiposity among HIV-infected female youth. Pediatr Infect Dis J 2018; 37: 1002–1007.
- 39.Cames C, Pascal L, Ba A, et al. Low prevalence of lipodystrophy in HIV-infected Senegalese children on long-term antiretroviral treatment: the ANRS 12279 MAGGSEN Pediatric Cohort Study. BMC Infect Dis 2018; 18: 374.
Citing Literature
