Skip to main content
Top
Published in: European Journal of Medical Research 6/2011

01-12-2011 | Research

Induction maintenance concept for HAART as initial treatment in HIV infected infants

Authors: S Ghosh, J Neubert, T Niehues, O Adams, N Morali-Karzei, A Borkhardt, HJ Laws

Published in: European Journal of Medical Research | Issue 6/2011

Login to get access

Abstract

Background

Early initiated antiretroviral therapy (ART) in HIV infected infants leads to improved long-term viral suppression and survival. Guidelines recommend initiating therapy with a triple ART consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either one additional non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Compared to older children and adults, viral relapse is seen more frequently in infants receiving triple ART. We now address the possibility of a more potent ART with a quadruple induction and triple maintenance therapy.

Methods

We examine the longitudinal course in four HIV infected infants, who were referred from other centers and could not be recruited to multicentre trials. We introduced ART initially consisting of two NRTIs, one NNRTI and one PI and later discontinued the PI at the age of 12 months maintaining a triple regime consisting of two NRTIs and one NNRTI.

Results

Provided that therapy adherence was maintained we observed an effective sustained decline of viral load and significant CD4 cell reconstitution even after switching to a triple regime. No drug associated toxicity was seen.

Conclusion

We suggest that a four drug therapy might be a possible initial therapy option in HIV infected infants, at least in those with a high viral load, followed by a maintenance triple regime after 12 months of therapy.
Literature
1.
go back to reference Welch S, Sharland M, Lyall EG, Tudor-Williams G, Niehues T, Wintergerst U, et al.: PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. HIV medicine 2009,10(10):591–613.PubMedCrossRef Welch S, Sharland M, Lyall EG, Tudor-Williams G, Niehues T, Wintergerst U, et al.: PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection. HIV medicine 2009,10(10):591–613.PubMedCrossRef
2.
go back to reference Children WGoATaMMoH-I: Guidelines for the Use of Antiretroviral Agents in Pediatric. HIV Infection 2009, 1–139. Children WGoATaMMoH-I: Guidelines for the Use of Antiretroviral Agents in Pediatric. HIV Infection 2009, 1–139.
3.
go back to reference Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, et al.: Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 2008,359(21):2233–44. 10.1056/NEJMoa0800971PubMedCentralPubMedCrossRef Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, et al.: Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 2008,359(21):2233–44. 10.1056/NEJMoa0800971PubMedCentralPubMedCrossRef
4.
go back to reference Goetghebuer T, Haelterman E, Le Chenadec J, Dollfus C, Gibb D, Judd A, et al.: Effect of early antiretroviral therapy on the risk of AIDS/death in HIV-infected infants. AIDS (London, England) 2009,23(5):597–604. 10.1097/QAD.0b013e328326ca37CrossRef Goetghebuer T, Haelterman E, Le Chenadec J, Dollfus C, Gibb D, Judd A, et al.: Effect of early antiretroviral therapy on the risk of AIDS/death in HIV-infected infants. AIDS (London, England) 2009,23(5):597–604. 10.1097/QAD.0b013e328326ca37CrossRef
5.
go back to reference PENPACT-1 First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial. The Lancet infectious diseases. Jan 31 PENPACT-1 First-line antiretroviral therapy with a protease inhibitor versus non-nucleoside reverse transcriptase inhibitor and switch at higher versus low viral load in HIV-infected children: an open-label, randomised phase 2/3 trial. The Lancet infectious diseases. Jan 31
6.
go back to reference Aboulker JP, Babiker A, Chaix ML, Compagnucci A, Darbyshire J, Debre M, et al.: Highly active antiretroviral therapy started in infants under 3 months of age: 72-week follow-up for CD4 cell count, viral load and drug resistance outcome. AIDS (London, England) 2004,18(2):237–45.CrossRef Aboulker JP, Babiker A, Chaix ML, Compagnucci A, Darbyshire J, Debre M, et al.: Highly active antiretroviral therapy started in infants under 3 months of age: 72-week follow-up for CD4 cell count, viral load and drug resistance outcome. AIDS (London, England) 2004,18(2):237–45.CrossRef
7.
go back to reference 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(19):1337–42. 10.1056/NEJM199705083361901PubMedCrossRef 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(19):1337–42. 10.1056/NEJM199705083361901PubMedCrossRef
8.
go back to reference Gulick RM, Ribaudo HJ, Shikuma CM, Lalama C, Schackman BR, Meyer WA, et al.: Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial. Jama. 2006,296(7):769–81.PubMed Gulick RM, Ribaudo HJ, Shikuma CM, Lalama C, Schackman BR, Meyer WA, et al.: Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial. Jama. 2006,296(7):769–81.PubMed
9.
go back to reference Luzuriaga K, McManus M, Mofenson L, Britto P, Graham B, Sullivan JL: A trial of three antiretroviral regimens in HIV-1-infected children. N Engl J Med 2004,350(24):2471–80. 10.1056/NEJMoa032706PubMedCrossRef Luzuriaga K, McManus M, Mofenson L, Britto P, Graham B, Sullivan JL: A trial of three antiretroviral regimens in HIV-1-infected children. N Engl J Med 2004,350(24):2471–80. 10.1056/NEJMoa032706PubMedCrossRef
10.
go back to reference Melvin AJ, Lewis PF, Mohan KM, Naugler WS, Frenkel LM: Efficacy and toxicity of antiretroviral therapy using 4 or more agents: application of a strategy for antiretroviral management in human immunodeficiency virus-infected children. Archives of pediatrics & adolescent medicine 2002,156(6):568–73.CrossRef Melvin AJ, Lewis PF, Mohan KM, Naugler WS, Frenkel LM: Efficacy and toxicity of antiretroviral therapy using 4 or more agents: application of a strategy for antiretroviral management in human immunodeficiency virus-infected children. Archives of pediatrics & adolescent medicine 2002,156(6):568–73.CrossRef
11.
go back to reference Orkin C, Stebbing J, Nelson M, Bower M, Johnson M, Mandalia S, et al.: A randomized study comparing a three- and four-drug HAART regimen in first-line therapy (QUAD study). J Antimicrob Chemother 2005,55(2):246–51. 10.1093/jac/dkh515PubMedCrossRef Orkin C, Stebbing J, Nelson M, Bower M, Johnson M, Mandalia S, et al.: A randomized study comparing a three- and four-drug HAART regimen in first-line therapy (QUAD study). J Antimicrob Chemother 2005,55(2):246–51. 10.1093/jac/dkh515PubMedCrossRef
12.
go back to reference Starr SE, Fletcher CV, Spector SA, Yong FH, Fenton T, Brundage RC, et al.: Combination therapy with efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors in children infected with human immunodeficiency virus type 1. Pediatric AIDS Clinical Trials Group 382 Team. N Engl J Med 1999,341(25):1874–81. 10.1056/NEJM199912163412502PubMedCrossRef Starr SE, Fletcher CV, Spector SA, Yong FH, Fenton T, Brundage RC, et al.: Combination therapy with efavirenz, nelfinavir, and nucleoside reverse-transcriptase inhibitors in children infected with human immunodeficiency virus type 1. Pediatric AIDS Clinical Trials Group 382 Team. N Engl J Med 1999,341(25):1874–81. 10.1056/NEJM199912163412502PubMedCrossRef
13.
go back to reference Tudor-Williams G, Head S, Weigel R, Valerius NH, Ridell A, Lyall EG: Baby Cocktail! A protease-sparing 4 drug combination for symptomatic infants. International Conference on AIDS 2002, 14. Tudor-Williams G, Head S, Weigel R, Valerius NH, Ridell A, Lyall EG: Baby Cocktail! A protease-sparing 4 drug combination for symptomatic infants. International Conference on AIDS 2002, 14.
14.
go back to reference DAIDS: National Institutes of Health, Division of AIDS Table for Grading the Severety of Adult and Pediatric Adverse Events, version 1.0. 2004. DAIDS: National Institutes of Health, Division of AIDS Table for Grading the Severety of Adult and Pediatric Adverse Events, version 1.0. 2004.
15.
go back to reference Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, et al.: Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clinical Immunol 2003,112(5):973–80. 10.1016/j.jaci.2003.07.003CrossRef Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, et al.: Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clinical Immunol 2003,112(5):973–80. 10.1016/j.jaci.2003.07.003CrossRef
16.
go back to reference Neubert J, Laws HJ, Adams O, Munk C, Kramer M, Niehues T, et al.: HIV-1 seroreversion following antiretroviral therapy in an HIV-infected child initially presenting with acquired immunodeficiency syndrome. AIDS (London, England) 24(2):327–8. Neubert J, Laws HJ, Adams O, Munk C, Kramer M, Niehues T, et al.: HIV-1 seroreversion following antiretroviral therapy in an HIV-infected child initially presenting with acquired immunodeficiency syndrome. AIDS (London, England) 24(2):327–8.
17.
go back to reference Chiappini E, Galli L, Tovo PA, Gabiano C, Gattinara GC, Guarino A, et al.: Virologic, immunologic, and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection. AIDS (London, England) 2006,20(2):207–15. 10.1097/01.aids.0000200529.64113.3eCrossRef Chiappini E, Galli L, Tovo PA, Gabiano C, Gattinara GC, Guarino A, et al.: Virologic, immunologic, and clinical benefits from early combined antiretroviral therapy in infants with perinatal HIV-1 infection. AIDS (London, England) 2006,20(2):207–15. 10.1097/01.aids.0000200529.64113.3eCrossRef
18.
go back to reference Chiappini E, Galli L, Tovo PA, Gabiano C, Lisi C, Bernardi S, et al.: Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy. BMC infectious diseases 2009, 9: 140. 10.1186/1471-2334-9-140PubMedCentralPubMedCrossRef Chiappini E, Galli L, Tovo PA, Gabiano C, Lisi C, Bernardi S, et al.: Five-year follow-up of children with perinatal HIV-1 infection receiving early highly active antiretroviral therapy. BMC infectious diseases 2009, 9: 140. 10.1186/1471-2334-9-140PubMedCentralPubMedCrossRef
Metadata
Title
Induction maintenance concept for HAART as initial treatment in HIV infected infants
Authors
S Ghosh
J Neubert
T Niehues
O Adams
N Morali-Karzei
A Borkhardt
HJ Laws
Publication date
01-12-2011
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 6/2011
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/2047-783X-16-6-243

Other articles of this Issue 6/2011

European Journal of Medical Research 6/2011 Go to the issue