International Journal of Infectious Diseases
Volume 14, Issue 1 , Pages e34-e40 , January 2010

Structured interruptions of highly active antiretroviral therapy in cycles of 4 weeks off/12 weeks on therapy in children having a chronically undetectable viral load cause progressively smaller viral rebounds

  • Gerardo C. Palacios

      Affiliations

    • Departamento de Pediatria and Infectologia Pediatrica, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 25 and Centro de Investigacion Biomedica del Noreste, Instituto Mexicano del Seguro Social, Fidel Velasquez y Lincoln S/N, Colonia Nueva Morelos, Monterrey, Nuevo Leon, CP 64320, Mexico
    • Corresponding Author InformationCorresponding author. Tel.: +52 81 8371 4100x41315; fax: +52 81 8371 4100x41315.
    • ,
  • Luz M. Sanchez

      Affiliations

    • Departamento de Pediatria and Infectologia Pediatrica, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 25 and Centro de Investigacion Biomedica del Noreste, Instituto Mexicano del Seguro Social, Fidel Velasquez y Lincoln S/N, Colonia Nueva Morelos, Monterrey, Nuevo Leon, CP 64320, Mexico
    • ,
  • Evangelina Briones

      Affiliations

    • Coordinacion Delegacional de Investigación en Salud, Instituto Mexicano del Seguro Social, Saltillo, Coahuila, Mexico
    • ,
  • Teresa J. Ramirez

      Affiliations

    • Laboratorio Estatal de Salud Publica del Estado de Nuevo Leon, Secretaria de Salud, Nuevo Leon, Mexico
    • ,
  • Hugo Castillo

      Affiliations

    • Laboratorio Estatal de Salud Publica del Estado de Nuevo Leon, Secretaria de Salud, Nuevo Leon, Mexico
    • ,
  • Lydia G. Rivera

      Affiliations

    • Laboratorio de Inmunologia y Virologia, Departamento de Microbiologia e Inmunologia, Facultad de Ciencias Biologicas, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon, Mexico
    • ,
  • Carlos A. Vazquez

      Affiliations

    • Departamento de Pediatria and Infectologia Pediatrica, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 25 and Centro de Investigacion Biomedica del Noreste, Instituto Mexicano del Seguro Social, Fidel Velasquez y Lincoln S/N, Colonia Nueva Morelos, Monterrey, Nuevo Leon, CP 64320, Mexico
    • ,
  • Cristina Rodriguez-Padilla

      Affiliations

    • Laboratorio de Inmunologia y Virologia, Departamento de Microbiologia e Inmunologia, Facultad de Ciencias Biologicas, Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon, Mexico
    • ,
  • Mark Holodniy

      Affiliations

    • California, USA
    • Corresponding Author InformationCorresponding author.

Received 5 November 2008 ,Revised 19 February 2009 ,Accepted 1 March 2009.

References 

  1. Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. February 28, 2008. Available at: http://aidsinfo.nih.gov/contentfiles/PediatricGuidelines (accessed March 2008).
  2. Sánchez-Granados JM, Ramos-Amador JT, Fernández-de-Miguel S, González-Tomée MI, Rojo-Conejo P, Vivas PF, et al. Impact of highly active antiretroviral therapy on the morbidity and mortality in Spanish human immunodeficiency virus-infected children. Pediatr Infect Dis J. 2003;22:863–867
  3. Palacios GC, Palafox VL, Alvarez MT, Vazquez G, Miranda G, Muñoz O, et al. Response to two consecutive protease inhibitor combination therapy regimens in a cohort of HIV-1 infected children. Scand J Infect Dis. 2002;34:41–44
  4. Sáez-Llorens X, Ramilo O. Early experience with protease inhibitors in human immunodeficiency virus-infected children. Pediatr Infect Dis J. 1998;17:728–738
  5. Solórzano-Santos F, Gochicoa-Rangel LG, Palacios-Saucedo G, Vázquez-Rosales G, Miranda-Novales MG. Hypertriglyceridemia and hypercholesterolemia in human immunodeficiency virus-infected children treated with protease inhibitors. Arch Med Res. 2006;37:129–132
  6. Plebani A, Esposito S, Pinzani R, Fesslova V, Bojanin J, Salice P, et al. Effect of highly active antiretroviral therapy on cardiovascular involvement in children with human immunodeficiency virus infection. Pediatr Infect Dis J. 2004;23:559–563
  7. Opravil M, Baumann D, Chave JP, Furrer H, Calmy A, Bernasconi E, et al. Long-term efficacy after switch from protease inhibitor-containing highly active antiretroviral therapy to abacavir, lamivudine, and zidovudine. AIDS. 2004;18:2213–2215
  8. Deeks SG, Wrin T, Liegler T, Hoh R, Hayden M, Barbour JD, et al. Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med. 2001;344:472–480
  9. Lori F, Lisziewicz J. Structured treatment interruptions for the management of HIV infection. JAMA. 2001;286:2981–2987
  10. Fagard C, Oxenius A, Günthard H, Garcia F, Le Braz M, Mestre G, et al. A prospective trial of structured treatment interruptions in human immunodeficiency virus infection. Arch Intern Med. 2003;163:1220–1226
  11. Yerly S, Günthard HF, Fagard C, Joos B, Perneger TV, Hirschel B, et al. Proviral HIV-DNA predicts viral rebound and viral setpoint after structured treatment interruptions. AIDS. 2004;18:1951–1953
  12. Lori F, Maserati R, Foli A, Seminari E, Timpone J, Lisziewicz J. Structured treatment interruptions to control HIV. Lancet. 2000;355:287–288
  13. Miller V, Sabin C, Hertogs K, Bloor S, Martinez-Picado J, D’Aquila R, et al. Virological and immunological effects of treatment interruptions in HIV-1 infected patients with treatment failure. AIDS. 2000;14:2857–2867
  14. Lori F, Lewis MG, Xu J, Varga G, Zinn DE, Crabbs C, et al. Control of HIV rebound through structured treatment interruptions during early infection. Science. 2000;290:1591–1593
  15. Giard M, Boibieux A, Ponceau B, Biron F, Braun E, Issartel B, et al. Treatment interruption in HIV infected patients: clinical and biological evolution. Med Malad Infect. 2005;35:525–529
  16. Gibb DM, Duong T, Leclezio VA, Walker AS, Verweel G, Dunn DT. Immunologic changes during unplanned treatment interruptions of highly active antiretroviral therapy in children with human immunodeficiency virus type 1 infection. Pediatr Infect Dis J. 2004;23:446–450
  17. Borkowsky W, Yogev R, Muresan P, McFarland E, Frenkel L, Fenton T, et al. Planned multiple exposures to autologous virus in HIV type 1-infected pediatric populations increases HIV-specific immunity and reduces HIV viremia. AIDS Res Hum Retroviruses. 2008;24:401–411
  18. Centers for Disease Control and Prevention (CDC). 1994 Revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR Recomm Rep 1994; 43(RR-12):1-10.
  19. In:  Lang T,  Secic M editor. How to report statistics in medicine Annotated guidelines for authors and reviewers. Philadelphia: American College of Physicians series; 1997;
  20. Centro Nacional para la Prevención y el Control del VIH/SIDA. Secretaría de Salud. Guía de manejo antirretroviral de las personas que viven con el VIH/SIDA. 2nd ed. México: Secretaría de Salud; 2005-2006. Available at: http://www.salud.gob.mx/conasida (accessed April 2009).
  21. Marchou B, Tangre P, Charreau I, Izopet J, Girard PM, May T, et al. Intermittent antiretroviral therapy in patients with controlled HIV infection. AIDS. 2007;21:457–466
  22. Bongiovanni M, Casana M, Tincati C, d’Arminio Monforte A. Treatment interruptions in HIV-infected subjects. J Antimicrob Chemother. 2006;58:502–505
  23. Julg B, Goebel FD. Treatment interruption in HIV therapy: a SMART strategy?. Infection. 2006;34:186–188
  24. The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355:2283-96.
  25. Sanchez R, Portilla J, Gimeno A, Boix V, Llopis C, Sanchez-Paya J, et al. Immunovirologic consequences and safety of short, non-structured interruptions of successful antiretroviral treatment. J Infect. 2007;54:159–166
  26. Pai NP, Tulsky JP, Lawrence J, Colford JM, Reingold AL. Structured treatment interruptions (STI) in chronic suppressed HIV infection in adults. Cochrane Database Syst Rev. 2005;4:CD005482
  27. Arnedo-Valero M, Garcia F, Gil C, Gvila T, Fumero E, Castro P, et al. Risk of selecting de novo drug-resistance mutations during structured treatment interruptions in patients with chronic HIV infection. Clin Infect Dis. 2005;41:883–890
  28. Ortiz GM, Wellons M, Brancato J, Vo HT, Zinn RL, Clarkson DE, et al. Structured antiretroviral treatment interruptions in chronically HIV-1infected subjects. Proc Natl Acad Sci USA. 2001;98:pp. 13288-93
  29. Currier JS, Baden LR. Getting smarter The toxicity of undertreated HIV infection. N Engl J Med. 2006;355:2359–2361
  30. Gibb DM, Compagnucci A, Green H, Lallemant M, Saidi Y, Ngo-Giang-Huong N, et al. Treatment interruption in children with chronic HIV-infection: the results of the Paediatric European Network for Treatment of AIDS (PENTA) 11 trial. 9th International Congress on Drug Therapy in HIV infection. Glasgow, Scotland. November 9-13, 2008. J Intern AIDS Soc 2008; 11(Suppl 1):O21.
  31. Diallo K, Götte M, Wainberg MA. Molecular impact of the M184 V mutation in human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother. 2003;47:3377–3383
  32. Trivedi V, Von Lindern J, Montes-Walters M, Rojo DR, Shell EJ, Parkin N, et al. Impact of human immunodeficiency virus type 1 reverse transcriptase inhibitor drug resistance mutation interactions on phenotypic susceptibility. AIDS Res Hum Retroviruses. 2008;24:1291–1300
  33. Shearer WT, Quinn TC, LaRussa P, Lew JF, Mofenson L, Almy S, et al. Viral load and disease progression in infants infected with human immunodeficiency virus type 1 Women and Infants Transmission Study Group. N Engl J Med. 1997;336:1337–1342
  34. McIntosh K, Shevitz A, Zaknun D, Kornegay J, Chatis P, Karthas N, et al. Age- and time-related changes in extracellular viral load in children vertically infected by human immunodeficiency virus. Pediatr Infect Dis J. 1996;15:1087–1091
  35. Bartlett JA, DeMasi R, Dawson D, Hill A. Variability in repeated consecutive measurements of plasma human immunodeficiency virus RNA in persons receiving stable nucleoside reverse transcriptase inhibitor therapy or no treatment. J Infect Dis. 1998;178:1803–1805
  36. Hughes MD, Johnson VA, Hirsch MMS, Bremer MJW, Elbeik T, Erice A, et al. Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response ACTG 241 Protocol Virology Substudy Team. Ann Intern Med. 1997;126:929–938
  37. Kilby JM, Goepfert PA, Miller AP, Gnann JW, Sillers M, Saag MS, et al. Recurrence of the acute HIV syndrome after interruption of antiretroviral therapy in a patient with chronic HIV infection: a case report. Ann Intern Med. 2000;133:435–438

PII: S1201-9712(09)00137-4

doi: 10.1016/j.ijid.2009.03.003

International Journal of Infectious Diseases
Volume 14, Issue 1 , Pages e34-e40 , January 2010

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