Intervention Review

You have free access to this content

Stavudine or zidovudine in three-drug combination therapy for initial treatment of HIV infection in antiretroviral-naïve individuals

  1. Alicen Spaulding1,*,
  2. George W Rutherford2,
  3. Nandi Siegfried3

Editorial Group: Cochrane HIV/AIDS Group

Published Online: 4 AUG 2010

Assessed as up-to-date: 8 JUL 2009

DOI: 10.1002/14651858.CD008651


How to Cite

Spaulding A, Rutherford GW, Siegfried N. Stavudine or zidovudine in three-drug combination therapy for initial treatment of HIV infection in antiretroviral-naïve individuals. Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD008651. DOI: 10.1002/14651858.CD008651.

Author Information

  1. 1

    University of Minnesota, Division of Epidemiology and Community Health, Minneapolis, Minnesota, USA

  2. 2

    University of California, San Francisco, Global Health Sciences, San Francisco, California, USA

  3. 3

    University of Cape Town, Department of Public Health and Primary Health Care, Cape Town, South Africa

*Alicen Spaulding, Division of Epidemiology and Community Health, University of Minnesota, 1300 S. Second Street, Suite 300, Minneapolis, Minnesota, 55454-1015, USA. alicenspaulding@yahoo.com.

Publication History

  1. Publication Status: Stable (no update expected for reasons given in 'What's new')
  2. Published Online: 4 AUG 2010

SEARCH

References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Carr 2000 (1 vs 2) {published data only}
  • Carr A, Chuah J, Hudson J, French M, Hoy J, Law M, Sayer D, Emery S, Cooper DA. A randomised, open-label comparison of three highly active antiretroviral therapy regimens including two nucleoside analogues and indinavir for previously untreated HIV-1 infection: the OzCombo I study. AIDS 2000;14:1171-80.
Carr 2000 (1 vs 3) {published data only}
  • Carr A, Chuah J, Hudson J, French M, Hoy J, Law M, Sayer D, Emery S, Cooper DA. A randomised, open-label comparison of three highly active antiretroviral therapy regimens including two nucleoside analogues and indinavir for previously untreated HIV-1 infection: the OzCombo I study. AIDS 2000;14:1171-80.
Eron 2000 {published data only}
  • Eron JJ Jr, Murphy RL, Peterson D, Pottage J, Parenti DM, Jemsek J, Swindells S, Sepulveda G, Bellos N, Rashbaum BC, Esinhart J, Schoellkopf N, Grosso R, Stevens M. A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: selection of thymidine analog regimen therapy (START II). AIDS 2000;14:1601-10.
French 2002 (1 vs 2) {published data only}
  • French M, Amin J, Roth N, Carr A, Law M, Emery S, Drummond F, Cooper D, OzCombo 2 investigators. Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 Infection: the OzCombo 2 study. HIV Clin Trials 2002;3:177-85.
French 2002 (1 vs 3) {published data only}
  • French M, Amin J, Roth N, Carr A, Law M, Emery S, Drummond F, Cooper D, OzCombo 2 investigators. Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 Infection: the OzCombo 2 study. HIV Clin Trials 2002;3:177-85.
Gathe 2002 {published data only}
  • Gathe J Jr, Badaro R, Grimwood A, Abrams L, Klesczewski K, Cross A, McLaren C. Antiviral activity of enteric-coated didanosine, stavudine, and nelfinavir versus zidovudine plus lamivudine and nelfinavir. J Acquir Immune Defic Syndr 2002;31:399-403.
Geijo Martinez 2006 {published data only}
  • Geijo Martínez MP, Maciá Martínez MA, Solera Santos J, Barberá Farré JR, Rodríguez Zapata M, Marcos Sánchez F, Martínez Alfaro E, Cuadra García-Tenorio F, Sanz Moreno J, Moreno Mendaña JM, Beato Pérez JL, Sanz Sanz J, GECMEI. Ensayo clínico comparativo de eficacia y seguridad de cuatro pautas de tratamiento antirretroviral de alta eficacia (TARGA) en pacientes con infección por VIH avanzada. Rev Clin Esp 2006; 206:67-76.. Rev Clin Esp 2006;206:67-76.
Kumar 2006 {published data only}
  • Kumar PN, Rodriguez-French A, Thompson MA, Tashima KT, Averitt D, Wannamaker PG, Williams VC, Shaefer MS, Pakes GE, Pappa KA, ESS40002 Study Team. A prospective, 96-week study of the impact of Trizivir, Combivir/nelfinavir and lamivudine/stavudine/nelfinavir on lipids, metabolic parameters and efficacy in antiretroviral-naïve patients: effect of sex and ethnicity. HIV Med 2006;7:85-98.
Li 2008 {published data only}
  • Li T, Dai Y, Kuang J, Jiang J, Han Y, Qiu Z, Xie J, Zuo L, Li Y. Three generic nevirapine-based antiretroviral treatments in Chinese HIV/AIDS patients: multicentric observation cohort. PLoS One 2008;3:e3918.
Robbins 2003 (EFV) {published data only}
  • Robbins GK, De Gruttola V, Shafer RW, Smeaton LM, Snyder SW, Pettinelli C, Dubé MP, Fischl MA, Pollard RB, Delapenha R, Gedeon L, van der Horst C, Murphy RL, Becker MI, D'Aquila RT, Vella S, Merigan TC, Hirsch MS, AIDS Clinical Trials Group 384 Team. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 2003;349:2293-202.
Robbins 2003 (NFV) {published data only}
  • Robbins GK, De Gruttola V, Shafer RW, Smeaton LM, Snyder SW, Pettinelli C, Dubé MP, Fischl MA, Pollard RB, Delapenha R, Gedeon L, van der Horst C, Murphy RL, Becker MI, D'Aquila RT, Vella S, Merigan TC, Hirsch MS, AIDS Clinical Trials Group 384 Team. Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 2003;349:2293-303.
Squires 2000 {published data only}
  • Squires KE, Gulick R, Tebas P, Santana J, Mulanovich V, Clark R, Yangco B, Marlowe SI, Wright D, Cohen C, Cooley T, Mauney J, Uffelman K, Schoellkopf N, Grosso R, Stevens M. A comparison of stavudine plus lamivudine versus zidovudine plus lamivudine in combination with indinavir in antiretroviral naive individuals with HIV infection: selection of thymidine analog regimen therapy (START I). AIDS 2000;14:1591-600.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Bussmann 2009 {published data only}
  • Bussmann H, Wester CW, Thomas A, Novitsky V, Okezie R, Muzenda T, Gaolathe T, Ndwapi N, Mawoko N, Widenfelt E, Moyo S, Musonda R, Mine M, Makhema J, Moffat H, Essex M, Degruttola V, Marlink RG. Response to zidovudine/didanosine-containing combination antiretroviral therapy among HIV-1 subtype C-infected adults in Botswana: two-year outcomes from a randomized clinical trial. J Acquir Immune Defic Syndr 2009;51:37-46.
Negredo 2004 {published data only}
  • Negredo E, Paredes R, Peroire J, Pedrol E, Côte H, Gel S, Fumaz CR, Ruiz L, Abril V, Rodriguez de Castrol E, Ochoa C, Martinez-Picado J, Montaner J, Rey-Joly C, Clotet B, Swatch Study Team. Alteration of antiretroviral drug regimens for HIV infection. Efficacy, safety and tolerability at week 96 of the Swatch Study. Antiviral Ther 2004;9:889-93.
Nieuwkirk 2001 {published data only}
  • Nieuwkirk PT, Gisolf EH, Reijers  MF, Lange JMA, Sanner SA, Sprangers MAG, NATIVE, PROMETHEUS and ADAM study groups. Long-term quality of life outcomes in three antiretroviral treatment strategies for HIV-1 infection. AIDS 2001;15:1985-93.
Rockstroh 2000 {published data only}
  • Rockstroh JK, Bergman F, Wiesl W, Rieke A, Theisen A, Fätkenheur G, Oettter M, Carls H, Fenske S, Nadler M, Knechten H, German Ritonavir/Indinavir Study Group. Efficacy and safety of twice daily first-line ritonavir/indinavir plus double nucleoside combination therapy in HIV-infected individuals. AIDS 2000;14:1181-85.
Shafer 2003 {published data only}
  • Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Johnson VA, Morse GD, Nokta MA, Martinez AI, Gripshover MB, Kaul P, Haubrich R, Swingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC, AIDS Clinical Trials Group 384 Team. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 2003;349:2304-15.
Shlay 2008 {published data only}
  • Shlay JC, Sharma S, Peng G, Gibert CL, Grunfeld C, Terry Beirn Community Programs for Clinical Research in AIDS, International Network for Strategic Initiatives in Global HIV Trials. Long-term subcutaneous tissue changes among antiretroviral-naive persons initiating stavudine, zidovudine, or abacavir with lamivudine. J Acquir Immune Defic Syndr 2008;48:53-62.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. Additional references
Amin 2003
  • Amin J, Moore A, Carr A, French MA, Law M, Emery S, Cooper DA, OzCombo 1 and 2 Investigators. Combined analysis of two-year follow-up from two open-label randomized trials comparing efficacy of three nucleoside reverse transcriptase inhibitor backbones for previously untreated HIV-1 infection: OzCombo 1 and 2. HIV Clin Trials 2003;4:252-61.
Bendavid 2009
Carr 1999a
  • Carr A, Hudson J, Chuah J, Law M, Hoy J. French MA, Emery S, Cooper D. The OzCombo 1 study: a randomised trial of combination antiretroviral therapy (ART) in treatment naive patients [Abstract OR102]. Australasian Society for HIV Medicine Conference, Perth, Australia, 9-11 December 1999.
Carr 1999b
  • Carr A, Hudson J, Hoy J, Chuah J, French M. OzCombo I: control of HIV replication in treatment naive patients in a randomised trial of HAART [Abstract 633]. Conference on Retroviruses and Opportunistic Infections, Boston, USA, 31 January-4 February 1999.
Division of AIDS 2009
  • Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Table for Grading the Severity of Adult and Pediatric Adverse Events. Bethesda, Maryland: National Institutes of Health, December 2004, Clarification 2009. Accessed 11 May 2010 at http://rcc.tech-res.com/Document/safetyandpharmacovigilance/DAIDS_AE_GradingTable_Clarification_August2009_Final.pdf.
Dube 2004
  • Dubé M, Zackin R, Parker R, Yang Y, Grinspoon S, Tebas P, Robbins G, Shafer R, Snyder S, Mulligan K.  Prospective study of glucose and lipid metabolism in antiretroviral-naive subjects randomized to receive nelfinavir, efavirenz, or Both Combined with zidovudine+lamivudine (ZDV+3TC) or didanosine+stavudine: A5005s, a substudy of ACTG 384 [Abstract 74]. 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, USA, 8-11 February 2004.
Dube 2005
  • Dubé MP, Parker RA, Tebas P, Grinspoon SK, Zackin RA, Robbins GK, Roubenoff R, Shafer RW, Wininger DA, Meyer WA 3rd, Snyder SW, Mulligan K. Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to nelfinavir or efavirenz plus dual nucleosides. AIDS 2005;19:1807-18.
Dube 2007a
  • Dubé MP, Komarow L, Mulligan K, Ginspoon SK, Parker RA, Robbins GK, Roubenoff R, Tebas P, Adult Clinical Trials Group 384. Long-term body fat outcomes in antiretroviral-naïve participants randomized to nelfinavir or efavirenz or both plus dual nucleosides. Dual X-ray absorpitometry results from A5005s, a substudy of Adult Clinical Trials Group 384. J Acquir Immune Defic Syndr 2007;45:508-14.
Dube 2007b
  • Dubé MP, Parker MA, Mulligan K, Tebas P, Robbins GK, Roubenoff R, Ginspoon SK. Effects of potent antiretroviral therapy on free testosterone levels and fat-free mass in men in a prospective, randomized trail: A5005s, a substudy of AIDS Clinical Trials Group 384. Clin Infect Dis 2007;45:120-6.
Eron 1998a
  • Eron J, Peterson D, Murphy R, Jemsek J, Pottage J, Parenti D, Esinhart J, Schoellkopf N, Stevens M. An open-label, randomized, comparative study of d4T + ddI + IDV versus ZDV + 3TC + IDV in treatment naive HIV  infected patients, START II [Abstract 381]. 5thConference on Retroviruses, Opportunistic Infections. Chicago, USA, 1-5 February 1998.
Eron 1998b
  • Eron J, Peterson D, Murphy R, Pottage J, Mauney J, Schoellkoph N, Stevens M. An open-label, randomized, comparative study of d4T + ddI + IDV versus ZDV + 3TC + IDV in treatment naive  HIV-infected patients (START II) [Abstract 12225]. International Conference on AIDS, Geneva, Switzerland, 28 June-3 July 1998.
Eron 2000
  • Eron JJ Jr, Murphy RL, Peterson D, Pottage J, Parenti DM, Jemsek J, Swindells S, Sepulveda G, Bellos N, Rashbaum BC, Esinhart J, Schoellkopf N, Grosso R, Stevens M. A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: selection of thymidine analog regimen therapy (START II). AIDS 2000;14:1601-10.
French 2002
  • French M, Amin J, Roth N, Carr A, Law M, Emery S, Drummond F, Cooper D, OzCombo 2 investigators. Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 Infection: the OzCombo 2 study. HIV Clin Trials 2002;3:177-85.
Gandhi 2006
  • Gandhi RT, Spritzler J, Chan E, Asmuth DM, Rodriguez B, Merigan TC, Hirsch MS, Shafer RW, Robbins GK, Pollard RB, ACTG 384 Team. Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr 2006;42:426-34.
Gilks 2006
  • Gilks CF, Crowley S, Ekpini R, Gove S, Perriens J, Souteyrand Y, Sutherland D, Vitoria M, Guerma T, De Cock K. The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings. Lancet 2006;368(9534):505-10.
GradePro 2008
  • Version 3.2 for Windows. [Computer program]. Jan Brozek, Andrew Oxman, Holger Schunemann. GRADE Working Group, 2008.
Gulick 1998
  • Gulick R. Combination therapy for patients with HIV-1 infection: the use of dual nucleoside analogues with protease inhibitors and other agents. AIDS 1998;12(Suppl 3):S17-22.
Guyatt 2008
  • Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schünemann HJ, GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924-6.
Higgins 2008
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions.Chichester: John Wiley & Sons Ltd, 2008.
Holtgrave 2005
Hudson 1998
  • Hudson J, Carr A, Cooper DA, Chuah J, Law M. OZCOMBO 1: A randomised, open-label, comparative, phase IV trial to evaluate the efficacy and safety of  triple drug combination antiretroviral regimens for the  treatment of HIV infection [Abstract 22348]. 12thInternational Conference on AIDS, Geneva, Switzerland, 28 June-3 July 1998.
Kumar 2003
  • Kumar P, Rodriguez-French A, Thompson M, Tashima K, Wannamaker P, Williams V, Pappa K. Prospective study of hyperlipidemia in ART-naïve subjects taking Trizivir (TZV), Combivir (COM)/nelfinavir (NFV), or stavudine (d4T)/lamivudine ((3TC)/NFV [Abstract 709]. 2nd IAS Conference on HIV Pathogenesis and Treatment, Paris, France, 13-17 July 2003.
Kumar 2004
  • Kumar P, Williams V, Tahima K, Rodriquez-French A, Thompson M, Wannamaker P, Hernandez J, Pappa K. Determinants of hyperlipidemia in ART-naive subjects treated with trizivir, combivir/nelfinavir, or stavudine/lamivudine  [Abstract 713]. 11thConference on Retroviruses, Opportunistic Infections. San Francisco, USA, 8-11 February 2004.
Laurent 2008
  • Laurent C, Bourgeois A, Mpoudi-Ngolé E, Ciaffi L, Kouanfack C, Mougnutou R, Nkoué N, Calmy A, Koulla-Shiro S, Delaporte E. Tolerability and effectiveness of first-line regimens combining nevirapine and lamivudine plus zidovudine or stavudine in Cameroon. AIDS Res Hum Retroviruses 2008;24:393-9.
Mulligan 2006
  • Mulligan K, Parker RA, Komarow L, Grinspoon SK, Tebas P, Robbins GK, Roubenoff R, Dubé MP. Mixed patterns of changes in central and peripheral fat following initiation of antiretroviral therapy in a randomized trial. J Acquir Immune Defic Syndr 2006;41:590-7.
Njoroge 2009
  • Njoroge J, Reidy W, John-Stewart G, Attwa M, Kiguru J, Ngumo R, Wambua N, Chung MH. Incidence of peripheral neuropathy among patients receiving HAART regimens containing stavudine vs. zidovudine in Kenya [Abstract TUPEB179]. 5th Conference on HIV Pathogenesis and Treatment and Prevention, Cape Town, South Africa, 19-22 July 2009.
Palella 1998
  • Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998;338:853-60.
Pavia 2002
  • Pavia A, Olson JS, Mauney J, Wills B. Differences in hematological complications in the selection of thymidine analog regimen therapy trials  (START I and START II) [Abstract TuPeB4499]. International Conference on AIDS, Barcelona, Spain, 7-12 July 2002.
Pazare 2008
  • Pazare AR, Khirsagar N, Gogatay N, Bajpai S. Comparative study of incidence of hyperlactetemia/ lactic acidosis in stavudine vs. AZT based regime [Abstract THPE0159]. XVII International AIDS Conference, Mexico City, Mexico, 3-8 August 2008.
Shafer 2003
  • Shafer RW, Smeaton LM, Robbins GK, De Gruttola V, Snyder SW, D'Aquila RT, Jonson VA, Morse GD, Nokota MA, Martinez AI, Gripshover BM, Kaul P, Haubrich R, Sweingle M, McCarty SD, Vella S, Hirsch MS, Merigan TC, AIDS Clinical Trials Group 384 Team. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 2003;349:2304-15.
Smeaton 2001
Squires 1998
  • Squires K, Gulick R, Santana J, Powderly W, Esinhart J, Schoellkopf N, Stevens M. An open-label, randomized, comparative study of d4T+3TC+IDV versus ZDV+3TC+IDV in treatment naive HIV-infected patients. START I [Abstract 380]. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, USA, 1-5 February 1998.
Squires 1999
  • Squires KE. An open-label, randomized, comparative study of  stavudine (d4T) + lamivudine (3TC) + indinavir (IDV)  versus zidovudine (ZDV) + 3TC + IDV in Treatment of  HIV-Infected Patients, START I [Abstract 506]. 39th Interscience Conference on Antimicrobial Agents and  Chemotherapy, San Francisco, USA, 26-29 September 1999.
Squires 2000a
  • Squires K, Gulick R, Pavia A, Eron J, Murphy R, Mauney J, Dale E. Sex differences in the selection of thymidine analog regimen therapy trials (START I and START II) [Abstract 516]. 7th Conference on Retroviruses and Opportunistic Infections, San Francisco, USA, 30 January-2 February 2000.
Torriani 2008
  • Torriani FJ, Komarow L, Parker RA, Cotter BR, Currier JS, Dubé MP, Fichtenbaum CJ, Gerschenson M, Mitchell CK, Murphy RL, Squires K, Stein, ACTG 5152s Study Team. Endothelial function in human immunodeficiency virus-infected antiretroviral-naïve subjects before and after starting potent antiretroviral therapy: the ACTG (AIDS Clinical Trials Group) Study 5152s). J Am Coll Cardiol 2008;52:569-76.
UNAIDS 2009
  • UNAIDS 2009 Report on global AIDS epidemic. Available online at: http://data.unaids.org/pub/Report/2009/2009_epidemic_update_en.pdf.Accessed December 15, 2009.
UNAIDS/WHO 2006
  • Joint United Nations Programme on HIV/AIDS, World Health Organization. Report on Joint WHO/UNAIDS Meeting on Forecasting ARV Needs Up to 2010, 7-8 November 2005, Geneva. Geneva, Switzerland: UNAIDS, WHO, 2006. Available at: http://www.who.int/hiv/amds/ReportForecastingMeeting.pdf. Accessed 12 August 2009.
WHO 2002
  • World Health Organization. Scaling Up Antiretroviral Therapy in Resource-Limited Settings. Guidelines for a Public Health Approach. Geneva, Switzerland: World Health Organization, 2002.
WHO 2003
  • World Health Organization. A Public Health Approach for Scaling Up Antiretroviral (ARV) Treatment. A Toolkit for Programme Managers. Geneva, Switzerland: World Health Organization, 2003.
WHO 2004
  • World Health Organization. Antiretroviral Drugs for Treatment Pregnant Women and Preventing HIV Infection in Infants. Guidelines on Care, Treatment and Support for Women Living with HIV/AIDS and Their Children in Resource-Constrained Settings. Geneva, Switzerland: World Health Organization, 2004.
WHO 2006a
  • World Health Organization. Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants: Towards Universal Access. Recommendations for a Public Health Approach. Geneva, Switzerland: World Health Organization, 2006.
WHO 2006b
  • World Health Organization. Antiretroviral Therapy for HIV infection in Adults and Adolescents: Recommendations for a Public Health Approach. 1996 Revision. Geneva, Switzerland: World Health Organization, 2006.
WHO 2006d
  • World Health Organization. Guidelines on Cotrimoxazole Prophylaxis for HIV-Related Infections among Children, Adolescents and Adults. Recommendations for a Public Health Approach. Geneva, Switzerland: World Health Organization, 2006.
WHO 2008
  • World Health Organization. Essential Prevention Interventions for Adults and Adolescents Living with HIV in Resource-Limited Settings. Geneva, Switzerland: World Health Organization, 2008.
WHO 2009
  • World Health Organization. Rapid Advice: Antiretroviral Therapy for HIV Infection in Adults and Adolescents. Geneva, Switzerland: World Health Organization, 2009.
WHO 2009a
  • Rapid advice: Antiretroviral therapy for HIV Infection in adults, adolescents. Accessed 28 June 2010 at http://www.who.int/hiv/pub/arv/rapid_advice_art.pdf.