A randomized clinical trial comparing metabolic parameters after 48 weeks of standard- and low-dose stavudine therapy and tenofovir disoproxil fumarate therapy in HIV-infected South African patients

HIV Medicine

Volumn 15, Issue 1, 2014, Pages 3-12

  Menezes, Colin N ^a,b   Crowther, Nj ^b   Duarte, R ^c   Van Amsterdam, D ^b   Evans, D ^b   Dickens, C ^c   Dix Peek, T ^c   Rassool, M ^b   Prinsloo, A ^b   Raal, F ^c   Sanne, I ^b  

^a UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^b UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^c UNIVERSITY OF THE WITWATERSRAND   (South Africa)

Author keywords

Glucose; Lipids; Randomized trial; Stavudine; Tenofovir disoproxil fumarate

Indexed keywords

ADIPONECTIN; C PEPTIDE; C REACTIVE PROTEIN; CYTOCHROME B; EFAVIRENZ; GLUCOSE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LAMIVUDINE; LEPTIN; LIPID; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MITOCHONDRIAL DNA; NUCLEAR RESPIRATORY FACTOR 1; STAVUDINE; TENOFOVIR DISOPROXIL; TRIACYLGLYCEROL;

ADIPOCYTE; ADULT; ANTIVIRAL THERAPY; ARM CIRCUMFERENCE; ARTICLE; BODY COMPOSITION; BODY FAT; BODY HEIGHT; BODY MASS; BODY WEIGHT; CAUSE OF DEATH; CD4 LYMPHOCYTE COUNT; CHEST CIRCUMFERENCE; CHOLESTEROL BLOOD LEVEL; CLINICAL FEATURE; CONTROLLED STUDY; CREATININE CLEARANCE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG SUBSTITUTION; DRUG WITHDRAWAL; FEMALE; FOLLOW UP; GENE DOSAGE; GENE EXPRESSION; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; HIP CIRCUMFERENCE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERLACTATEMIA; INFLAMMATION; INSULIN BLOOD LEVEL; KIDNEY DYSFUNCTION; LACTIC ACIDOSIS; LIPID METABOLISM; LIPOATROPHY; LIPOPROTEIN BLOOD LEVEL; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; METABOLIC PARAMETERS; MITOCHONDRIAL TOXICITY; OPEN STUDY; OUTCOME ASSESSMENT; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; PROSPECTIVE STUDY; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SKINFOLD THICKNESS; THIGH CIRCUMFERENCE; TREATMENT DURATION; TRIACYLGLYCEROL BLOOD LEVEL; VIRUS LOAD; WAIST CIRCUMFERENCE;

GLUCOSE; LIPIDS; RANDOMIZED TRIAL; STAVUDINE; TENOFOVIR DISOPROXIL FUMARATE;

ADENINE; ADULT; ANALYSIS OF VARIANCE; ANTHROPOMETRY; ANTI-HIV AGENTS; BENZOXAZINES; BIOLOGICAL MARKERS; BODY COMPOSITION; DNA, MITOCHONDRIAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SUBSTITUTION; FEMALE; GLUCOSE; HIV INFECTIONS; HUMANS; INFLAMMATION; LAMIVUDINE; LIPID METABOLISM; MALE; MIDDLE AGED; PHOSPHOROUS ACIDS; SOUTH AFRICA; STAVUDINE;

EID: 84888868936     PISSN: 14642662     EISSN: 14681293     Source Type: Journal    
DOI: 10.1111/hiv.12074     Document Type: Article

References (45)

1. Palella FJ Jr, Delaney KM, Moorman AC etal. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338: 853-860.
2. Hogg RS, O'Shaughnessy MV, Gataric N etal. Decline in deaths from AIDS due to new antiretrovirals. Lancet 1997; 349: 1294.
3. Menezes CN, Maskew M, Sanne I, Crowther NJ, Raal FJ. A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects. BMC Infect Dis 2011; 11: 244.
4. Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999; 353: 2093-2099.
5. Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet 2000; 356: 1423-1430.
6. Galli M, Ridolfo AL, Adorni F etal. Body habitus changes and metabolic alterations in protease inhibitor-naive HIV-1-infected patients treated with two nucleoside reverse transcriptase inhibitors. J Acquir Immune Defic Syndr 2002; 29: 21-31.
7. Friis-Møller N, Sabin CA, Weber R etal. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003; 349: 1993-2003.
8. Lindegaard B, Keller P, Bruunsgaard H, Gerstoft J, Pedersen BK. Low plasma level of adiponectin is associated with stavudine treatment and lipodystrophy in HIV-infected patients. Clin Exp Immunol 2004; 135: 273-279.
9. Palios J, Kadoglou NP, Lampropoulos S. The pathophysiology of HIV-HAART-related metabolic syndrome leading to cardiovascular disorders: the emerging role of adipokines. Exp Diabetes Res 2012; 2012: 103063.
10. Reingold J, Wanke C, Kotler D etal. Association of HIV infection and HIV/HCV coinfection with C-reactive protein levels: the fat redistribution and metabolic change in HIV infection (FRAM) study. J Acquir Immune Defic Syndr 2008; 48: 142-148.
11. Rutter MK, Meigs JB, Sullivan LM, D'Agostino RB, Wilson PW. C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Frammingham Offspring study. Circulation 2004; 110: 380-385.
12. Pai JK, Pischon T, Ma J etal. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med 2004; 351: 2599-2610.
13. Triant VA, Meigs JB, Grinspoon SK. Association of C-reactive protein and HIV infection with acute myocardial infarction. J Acquir Immune Defic Syndr 2009; 51: 268-273.
14. Boulle A, Orrell C, Kaplan R etal. Substitution due to antiretroviral toxicity or contraindication in the first 3 years of antiretroviral treatment in a large South African cohort. Antivir Ther 2007; 12: 753-760.
15. Mutimura E, Stewart A, Rheeder P, Crowther NJ. Metabolic function and the prevalence of lipodystrophy in a population of HIV-infected African subjects receiving highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2007; 46: 451-455.
16. van Griensven J, Zachariah R, Rasschaert F, Mugabo J, Atte EF, Reid T. Stavudine- and nevirapine-related drug toxicity while on generic fixed-dose antiretroviral treatment: incidence, timing and risk factors in a three-year cohort in Kigali, Rwanda. Trans R Soc Trop Med Hyg 2010; 104: 148-153.
17. World Health Organization. Forecasting antiretroviral demand. 2010. Available at www.who.int/hiv/amds/forecasting/en/index4.html (accessed 20 April 2013).
18. National Department of Health. National Antiretroviral Treatment Guidelines, First Edition 2004: Available at www.doh.gov.za/docs/misc/2004/sec1.pdf (accessed 20 April 2013).
19. National Department of Health South Africa. 2010. Clinical guidelines for the management of HIV & AIDS in adults and adolescents: Available at www.health-e.org.za/documents/0ba405d9042e557a9fb1987adb68cb97.pdf (accessed 20 April 2013).
20. Schowalter L, Conradie F. Approaches to tenofovir and abacavir drug shortages in South Africa: a guide for clinicians. South Afr J HIV Med 2012; 13: 56-57.
21. Gallant JE, Staszewski S, Pozniak AL etal. Efficacy and safety of tenofovir DF vs. stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004; 292: 191-201.
22. Overton ET, Nurutdinova D, Freeman J, Seyfried W, Mondy KE. Factors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapy. HIV Med 2009; 10: 343-350.
23. Gallant JE, Parish MA, Keruly JC, Moore RD. Changes in renal function associated with tenofovir disoproxil fumarate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment. Clin Infect Dis 2005; 40: 1194-1198.
24. Young B, Buchacz K, Baker RK etal. Renal function in tenofovir exposed and tenofovir-unexposed patients receiving highly active antiretroviral therapy in the HIV Outpatient Study. J Int Assoc Physicians AIDS Care (Chic Ill) 2007; 6: 178-187.
25. Ryom L, Mocroft A, Kirk O etal. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study. J Infect Dis 2013; 207: 1359-1369.
26. Fux CA, Simcock M, Wolbers M etal. Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study. Antivir Ther 2007; 12: 1165-1173.
27. Milinkovic A, Martinez E, López S etal. The impact of reducing stavudine dose versus switching to tenofovir on plasma lipids, body composition and mitochondrial function in HIV-infected patients. Antivir Ther 2007; 12: 407-415.
28. McComsey GA, LoRe III V, O'Riordan M etal. Effect of Reducing the Dose of Stavudine on Body Composition, Bone Density and Markers of Mitochondrial Toxicity in HIV infected Subjects- a Randomized, Controlled study. Clin Infect Dis 2008; 46: 1290-1296.
29. Hill A, Ruxrungtham K, Hanvanich M etal. Systematic review of clinical trials evaluating low doses of stavudine as part of antiretroviral treatment. Expert Opin Pharmacother 2007; 8: 679-688.
30. Menezes CN, Duarte R, Dickens C etal. The early effects of stavudine compared to tenofovir on adipocyte gene expression, mitochondrial DNA copy number and metabolic parameters in South African HIV-infected patients: a randomized trial. HIV Med 2013; 14: 217-225.
31. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41.
32. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419.
33. Nolan D, Hammond E, Martin A etal. Mitochondrial DNA depletion and morphologic changes in adipocytes associated with nucleoside reverse transcriptase inhibitor therapy. AIDS 2003; 17: 1329-1338.
34. Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143-3421.
35. Rosen S, Long L, Fox M, Sanne I. Cost and cost-effectiveness of switching from stavudine to tenofovir in first-line antiretroviral regimens in South Africa. J Acquir Immune Defic Syndr 2008; 48: 334-344.
36. Mallon PW, Miller J, Cooper DA, Carr A. Prospective evaluation of the effects of antiretroviral therapy on body composition in HIV-1-infected men starting therapy. AIDS 2003; 17: 971-979.
37. Magkos F, Mantzoros CS. Body fat redistribution and metabolic abnormalities in HIV-infected patients on highly active antiretroviral therapy: novel insights into pathophysiology and emerging opportunities for treatment. Metabolism 2011; 60: 749-753.
38. De Wit S, Sabin CA, Weber R etal. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Diabetes Care 2008; 31: 1224-1229.
39. Savès M, Raffi F, Capeau J etal. Factors related to lipodystrophy and metabolic alterations in patients with human immunodeficiency virus infection receiving highly active antiretroviral therapy. Clin Infect Dis 2002; 34: 1396-1405.
40. Shlay JC, Visnegarwala F, Bartsch G etal. Body composition and metabolic changes in antiretroviral-naive patients randomized to didanosine and stavudine vs. abacavir and lamivudine. J Acquir Immune Defic Syndr 2005; 38: 147-155.
41. Constans J, Pellegrin JL, Peuchant E etal. Plasma lipids in HIV-infected patients: a prospective study in 95 patients. Eur J Clin Invest 1994; 24: 416-420.
42. Gallant JE, DeJesus E, Arribas JR etal. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med 2006; 354: 251-260.
43. Calmy A, Gayet-Ageron A, Montecucco F etal. HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS 2009; 23: 929-939.
44. Dzwonek AB, Novelli V, Schwenk A. Serum leptin concentrations and fat distribution in HIV-1 infected children on highly active antiretroviral therapy. HIV Med 2007; 8: 433-438.
45. Bezante GP, Briatore L, Rollando D etal. Hypoadiponectinemia in lipodystrophic HIV individuals: a metabolic marker of subclinical cardiac damage. Nutr Metab Cardiovasc Dis 2009; 19: 277-282.