Skip to main content
Top
Published in: BMC Infectious Diseases 1/2006

Open Access 01-12-2006 | Research article

Impact of long-term viral suppression in CD4+ recovery of HIV-children on Highly Active Antiretroviral Therapy

Authors: Salvador Resino, Rosa Resino, Juan A Leon, José M Bellon, Pablo Martin-Fontelos, Jose T Ramos, Dolores Gurbindo-Gutierrez, Maria I de Jose, Luis Ciria, Maria A Muñoz-Fernandez

Published in: BMC Infectious Diseases | Issue 1/2006

Login to get access

Abstract

Background

The effects of HAART may differ between children and adults because children have a developing immune system, and the long-term immunological outcome in HIV-infected children on HAART is not well-known. A major aim of our study was to determine CD4+ evolution associated with long-term VL control during 4 years of observation on HAART.

Methods

We carried out a retrospective study on a cohort of 160 vertically HIV-infected children. It was carried out from 1996 to 2004 in six large Spanish pediatric referral hospitals. We compared 33 children who had long-term VL suppression (VL ≤400 copies/ml) in the first 12 months of follow-up and maintained that level throughout follow-up (Responders-group), and 127 children with persistently detectable VL in spite of ART switches (Non-Responders-group).

Results

We observed a quick initial and significant increase in CD4+ counts from the baseline to 12 months on HAART in both groups (p < 0.01). The Non-Responders group sustained CD4+ increases and most of these children maintained high CD4+ level counts (≥25%). The Non-Responders group reached a plateau between 26% and 27% CD4+ at the first 12 months of follow-up that remained stable during the following 3 years. However, the Responders group reached a plateau between 30% and 32% CD4+ at 24, 36 and 48 months of follow-up. We found that the Responders group had higher CD4+ count values and higher percentages of children with CD4+ ≥25% than the Non-Responders group (p < 0.05) after month 12.

Conclusion

Long-term VL suppression in turn induces large beneficial effects in immunological responses. However, it is not indispensable to recover CD4+ levels.
Appendix
Available only for authorised users
Literature
1.
go back to reference Resino S, Bellón JM, Gurbindo D, Ramos JT, León JA, Mellado MJ, Muñoz-Fernández MA: Viral Load and CD4+ T-Cells Response to HAART in HIV-Infected Children: a Observational Study. Clin Infect Dis. 2003, 37: 1216-1225. 10.1086/378804.CrossRefPubMed Resino S, Bellón JM, Gurbindo D, Ramos JT, León JA, Mellado MJ, Muñoz-Fernández MA: Viral Load and CD4+ T-Cells Response to HAART in HIV-Infected Children: a Observational Study. Clin Infect Dis. 2003, 37: 1216-1225. 10.1086/378804.CrossRefPubMed
2.
go back to reference Borkowsky W, Stanley K, Douglas SD, Lee S, Wiznia A, Pelton S, Yogev R, McIntosh K, Nachman S: Immunologic response to combination nucleoside analogue plus protease inhibitor therapy in stable antiretroviral therapy-experienced human immunodeficiency virus-infected children. J Infect Dis. 2000, 182: 96-103. 10.1086/315672.CrossRefPubMed Borkowsky W, Stanley K, Douglas SD, Lee S, Wiznia A, Pelton S, Yogev R, McIntosh K, Nachman S: Immunologic response to combination nucleoside analogue plus protease inhibitor therapy in stable antiretroviral therapy-experienced human immunodeficiency virus-infected children. J Infect Dis. 2000, 182: 96-103. 10.1086/315672.CrossRefPubMed
3.
go back to reference Resino S, Bellón JM, Resino R, Navarro ML, Ramos JT, Mellado MJ, de Jose MI, Muñoz-Fernández MA: Extensive implementation of highly active antiretroviral therapy shows great effectiveness on the survival and surrogate markers in vertically HIV-infected children. Clin Infect Dis. 2004, 38: 1605-1612. 10.1086/420738.CrossRefPubMed Resino S, Bellón JM, Resino R, Navarro ML, Ramos JT, Mellado MJ, de Jose MI, Muñoz-Fernández MA: Extensive implementation of highly active antiretroviral therapy shows great effectiveness on the survival and surrogate markers in vertically HIV-infected children. Clin Infect Dis. 2004, 38: 1605-1612. 10.1086/420738.CrossRefPubMed
4.
go back to reference Wiznia A, Stanley K, Krogstad P, Johnson G, Lee S, McNamara J, Moye J, Jackson JB, Mendez H, Aguayo R, Dieudonne A, Kovacs A, Bamji M, Abrams E, Rana S, Sever J, Nachman S: Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy- experienced HIV-infected children: week 24 results of a randomized controlled trial--PACTG 377. Pediatric AIDS Clinical Trials Group 377 Study Team. AIDS Res Hum Retroviruses. 2000, 16: 1113-1121. 10.1089/088922200414956.CrossRefPubMed Wiznia A, Stanley K, Krogstad P, Johnson G, Lee S, McNamara J, Moye J, Jackson JB, Mendez H, Aguayo R, Dieudonne A, Kovacs A, Bamji M, Abrams E, Rana S, Sever J, Nachman S: Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy- experienced HIV-infected children: week 24 results of a randomized controlled trial--PACTG 377. Pediatric AIDS Clinical Trials Group 377 Study Team. AIDS Res Hum Retroviruses. 2000, 16: 1113-1121. 10.1089/088922200414956.CrossRefPubMed
5.
go back to reference van Rossum AM, Geelen SP, Hartwig NG, Wolfs TF, Weemaes CM, Scherpbier HJ, van Lochem EG, Hop WC, Schutten M, Osterhaus AD, Burger DM, de Groot R: Results of 2 years of treatment with protease-inhibitor--containing antiretroviral therapy in dutch children infected with human immunodeficiency virus type 1. Clin Infect Dis. 2002, 34: 1008-1016. 10.1086/339443.CrossRefPubMed van Rossum AM, Geelen SP, Hartwig NG, Wolfs TF, Weemaes CM, Scherpbier HJ, van Lochem EG, Hop WC, Schutten M, Osterhaus AD, Burger DM, de Groot R: Results of 2 years of treatment with protease-inhibitor--containing antiretroviral therapy in dutch children infected with human immunodeficiency virus type 1. Clin Infect Dis. 2002, 34: 1008-1016. 10.1086/339443.CrossRefPubMed
6.
go back to reference Soh CH, Oleske JM, Brady MT, Spector SA, Borkowsky W, Burchett SK, Foca MD, Handelsman E, Jimenez E, Dankner WM, Hughes MD: Long-term effects of protease-inhibitor-based combination therapy on CD4 T-cell recovery in HIV-1-infected children and adolescents. Lancet. 2003, 362: 2045-2051. 10.1016/S0140-6736(03)15098-2.CrossRefPubMed Soh CH, Oleske JM, Brady MT, Spector SA, Borkowsky W, Burchett SK, Foca MD, Handelsman E, Jimenez E, Dankner WM, Hughes MD: Long-term effects of protease-inhibitor-based combination therapy on CD4 T-cell recovery in HIV-1-infected children and adolescents. Lancet. 2003, 362: 2045-2051. 10.1016/S0140-6736(03)15098-2.CrossRefPubMed
7.
go back to reference Holmberg SD, Hamburger ME, Moorman AC, Wood KC, Palella FJJ: Factors associated with maintenance of long-term plasma human immunodeficiency virus RNA suppression. Clin Infect Dis. 2003, 37: 702-707. 10.1086/376992.CrossRefPubMed Holmberg SD, Hamburger ME, Moorman AC, Wood KC, Palella FJJ: Factors associated with maintenance of long-term plasma human immunodeficiency virus RNA suppression. Clin Infect Dis. 2003, 37: 702-707. 10.1086/376992.CrossRefPubMed
8.
go back to reference Resino S, Galan I, Perez A, Leon JA, Seoane E, Gurbindo D, Muñoz-Fernández MA: HIV-infected children with moderate-severe immune-suppression: changes in the immune system after highly active antiretroviral therapy. Clin Exp Immunol. 2004, 137: 570-577. 10.1111/j.1365-2249.2004.02583.x.CrossRefPubMedPubMedCentral Resino S, Galan I, Perez A, Leon JA, Seoane E, Gurbindo D, Muñoz-Fernández MA: HIV-infected children with moderate-severe immune-suppression: changes in the immune system after highly active antiretroviral therapy. Clin Exp Immunol. 2004, 137: 570-577. 10.1111/j.1365-2249.2004.02583.x.CrossRefPubMedPubMedCentral
9.
go back to reference Douek DC, Picker LJ, Koup RA: T cell dynamics in HIV-1 infection. Annu Rev Immunol. 2003, 21: 265-304. 10.1146/annurev.immunol.21.120601.141053.CrossRefPubMed Douek DC, Picker LJ, Koup RA: T cell dynamics in HIV-1 infection. Annu Rev Immunol. 2003, 21: 265-304. 10.1146/annurev.immunol.21.120601.141053.CrossRefPubMed
10.
go back to reference Chiappini E, Galli L, Zazzi M, de Martino M: Immunological recovery despite virological failure is independent of human immunodeficiency virus-type 1 resistant mutants in children receiving highly active antiretroviral therapy. J Med Virol. 2003, 70: 506-512. 10.1002/jmv.10424.CrossRefPubMed Chiappini E, Galli L, Zazzi M, de Martino M: Immunological recovery despite virological failure is independent of human immunodeficiency virus-type 1 resistant mutants in children receiving highly active antiretroviral therapy. J Med Virol. 2003, 70: 506-512. 10.1002/jmv.10424.CrossRefPubMed
11.
go back to reference Peruzzi M, Azzari C, Galli L, Vierucci A, De Martino M: Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure. Clin Exp Immunol. 2002, 128: 365-371. 10.1046/j.1365-2249.2002.01814.x.CrossRefPubMedPubMedCentral Peruzzi M, Azzari C, Galli L, Vierucci A, De Martino M: Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure. Clin Exp Immunol. 2002, 128: 365-371. 10.1046/j.1365-2249.2002.01814.x.CrossRefPubMedPubMedCentral
12.
go back to reference Melvin AJ, Rodrigo AG, Mohan KM, Lewis PA, Manns-Arcuino L, Coombs RW, Mullins JI, Frenkel LM: HIV-1 dynamics in children. J Acquir Immune Defic Syndr Hum Retrovirol. 1999, 20: 508-513.CrossRef Melvin AJ, Rodrigo AG, Mohan KM, Lewis PA, Manns-Arcuino L, Coombs RW, Mullins JI, Frenkel LM: HIV-1 dynamics in children. J Acquir Immune Defic Syndr Hum Retrovirol. 1999, 20: 508-513.CrossRef
13.
go back to reference Deeks SG, Barbour JD, Grant RM, Martin JN: Duration and predictors of CD4 T-cell gains in patients who continue combination therapy despite detectable plasma viremia. AIDS. 2002, 16: 201-207. 10.1097/00002030-200201250-00009.CrossRefPubMed Deeks SG, Barbour JD, Grant RM, Martin JN: Duration and predictors of CD4 T-cell gains in patients who continue combination therapy despite detectable plasma viremia. AIDS. 2002, 16: 201-207. 10.1097/00002030-200201250-00009.CrossRefPubMed
14.
go back to reference Resino S, Bellón JM, Ramos JT, Gonzalez-Rivera M, de José MI, González MI, Gurbindo D, Mellado MJ, Cabrero E, Muñoz-Fernández MA: Positive virologic outcome after lopinavir/ritonavir salvage therapy in protease inhibitor-experienced HIV-1-infected children. A prospective cohort study. J Antimicrob Chemother. 2004, 54: 921-931. 10.1093/jac/dkh431.CrossRefPubMed Resino S, Bellón JM, Ramos JT, Gonzalez-Rivera M, de José MI, González MI, Gurbindo D, Mellado MJ, Cabrero E, Muñoz-Fernández MA: Positive virologic outcome after lopinavir/ritonavir salvage therapy in protease inhibitor-experienced HIV-1-infected children. A prospective cohort study. J Antimicrob Chemother. 2004, 54: 921-931. 10.1093/jac/dkh431.CrossRefPubMed
15.
go back to reference Paul ME, Mao C, Charurat M, Serchuck L, Foca M, Hayani K, Handelsman EL, Diaz C, McIntosh K, Shearer WT: Predictors of immunologic long-term nonprogression in HIV-infected children: Implications for initiating therapy. J Allergy Clin Immunol. 2005, 115: 848-855. 10.1016/j.jaci.2004.11.054.CrossRefPubMed Paul ME, Mao C, Charurat M, Serchuck L, Foca M, Hayani K, Handelsman EL, Diaz C, McIntosh K, Shearer WT: Predictors of immunologic long-term nonprogression in HIV-infected children: Implications for initiating therapy. J Allergy Clin Immunol. 2005, 115: 848-855. 10.1016/j.jaci.2004.11.054.CrossRefPubMed
16.
go back to reference Koletar SL, Williams PL, Wu J, McCutchan JA, Cohn SE, Murphy RL, Lederman HM, Currier JS: Long-term follow-up of HIV-infected individuals who have significant increases in CD4+ cell counts during antiretroviral therapy. Clin Infect Dis. 2004, 39: 1500-1506. 10.1086/424882.CrossRefPubMed Koletar SL, Williams PL, Wu J, McCutchan JA, Cohn SE, Murphy RL, Lederman HM, Currier JS: Long-term follow-up of HIV-infected individuals who have significant increases in CD4+ cell counts during antiretroviral therapy. Clin Infect Dis. 2004, 39: 1500-1506. 10.1086/424882.CrossRefPubMed
17.
go back to reference Deeks SG, Barbour JD, Martin JN, Swanson MS, Grant RM: Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection. J Infect Dis. 2000, 181: 946-953. 10.1086/315334.CrossRefPubMed Deeks SG, Barbour JD, Martin JN, Swanson MS, Grant RM: Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection. J Infect Dis. 2000, 181: 946-953. 10.1086/315334.CrossRefPubMed
18.
go back to reference Kaufmann GR, Bloch M, Finlayson R, Zaunders J, Smith D, Cooper DA: The extent of HIV-1-related immunodeficiency and age predict the long- term CD4 T lymphocyte response to potent antiretroviral therapy. Aids. 2002, 16: 359-367. 10.1097/00002030-200202150-00007.CrossRefPubMed Kaufmann GR, Bloch M, Finlayson R, Zaunders J, Smith D, Cooper DA: The extent of HIV-1-related immunodeficiency and age predict the long- term CD4 T lymphocyte response to potent antiretroviral therapy. Aids. 2002, 16: 359-367. 10.1097/00002030-200202150-00007.CrossRefPubMed
19.
go back to reference Tarwater PM, Margolick JB, Jin J, Phair JP, Detels R, Rinaldo C, Giorgi J, Munoz A: Increase and plateau of CD4 T-cell counts in the 3(1/2) years after initiation of potent antiretroviral therapy. J Acquir Immune Defic Syndr. 2001, 27: 168-175.CrossRefPubMed Tarwater PM, Margolick JB, Jin J, Phair JP, Detels R, Rinaldo C, Giorgi J, Munoz A: Increase and plateau of CD4 T-cell counts in the 3(1/2) years after initiation of potent antiretroviral therapy. J Acquir Immune Defic Syndr. 2001, 27: 168-175.CrossRefPubMed
20.
go back to reference Hunt PW, Deeks SG, Rodriguez B, Valdez H, Shade SB, Abrams DI, Kitahata MM, Krone M, Neilands TB, Brand RJ, Lederman MM, Martin JN: Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy. Aids. 2003, 17: 1907-1915. 10.1097/00002030-200309050-00009.CrossRefPubMed Hunt PW, Deeks SG, Rodriguez B, Valdez H, Shade SB, Abrams DI, Kitahata MM, Krone M, Neilands TB, Brand RJ, Lederman MM, Martin JN: Continued CD4 cell count increases in HIV-infected adults experiencing 4 years of viral suppression on antiretroviral therapy. Aids. 2003, 17: 1907-1915. 10.1097/00002030-200309050-00009.CrossRefPubMed
21.
go back to reference Franco JM, Leon-Leal JA, Leal M, Cano-Rodriguez A, Pineda JA, Macias J, Rubio A, Rey C, Sanchez B, Lissen E: CD4+ and CD8+ T lymphocyte regeneration after anti-retroviral therapy in HIV-1-infected children and adult patients. Clin Exp Immunol. 2000, 119: 493-498. 10.1046/j.1365-2249.2000.01152.x.CrossRefPubMedPubMedCentral Franco JM, Leon-Leal JA, Leal M, Cano-Rodriguez A, Pineda JA, Macias J, Rubio A, Rey C, Sanchez B, Lissen E: CD4+ and CD8+ T lymphocyte regeneration after anti-retroviral therapy in HIV-1-infected children and adult patients. Clin Exp Immunol. 2000, 119: 493-498. 10.1046/j.1365-2249.2000.01152.x.CrossRefPubMedPubMedCentral
22.
go back to reference Jimenez JL, Resino S, Martinez-Colom A, Bellon JM, Munoz-Fernandez MA: Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopinavir/ritonavir therapy. J Antimicrob Chemother. 2005. Jimenez JL, Resino S, Martinez-Colom A, Bellon JM, Munoz-Fernandez MA: Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopinavir/ritonavir therapy. J Antimicrob Chemother. 2005.
23.
go back to reference Harrigan PR, Hogg RS, Dong WW, Yip B, Wynhoven B, Woodward J, Brumme CJ, Brumme ZL, Mo T, Alexander CS, Montaner JS: Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy. J Infect Dis. 2005, 191: 339-347. 10.1086/427192.CrossRefPubMed Harrigan PR, Hogg RS, Dong WW, Yip B, Wynhoven B, Woodward J, Brumme CJ, Brumme ZL, Mo T, Alexander CS, Montaner JS: Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy. J Infect Dis. 2005, 191: 339-347. 10.1086/427192.CrossRefPubMed
24.
go back to reference Watson DC, Farley JJ: Efficacy of and adherence to highly active antiretroviral therapy in children infected with human immunodeficiency virus type 1. Pediatr Infect Dis J. 1999, 18: 682-689. 10.1097/00006454-199908000-00006.CrossRefPubMed Watson DC, Farley JJ: Efficacy of and adherence to highly active antiretroviral therapy in children infected with human immunodeficiency virus type 1. Pediatr Infect Dis J. 1999, 18: 682-689. 10.1097/00006454-199908000-00006.CrossRefPubMed
25.
go back to reference Reddington C, Cohen J, Baldillo A, Toye M, Smith D, Kneut C, Demaria A, Bertolli J, Hsu HW: Adherence to medication regimens among children with human immunodeficiency virus infection. Pediatr Infect Dis J. 2000, 19: 1148-1153.CrossRefPubMed Reddington C, Cohen J, Baldillo A, Toye M, Smith D, Kneut C, Demaria A, Bertolli J, Hsu HW: Adherence to medication regimens among children with human immunodeficiency virus infection. Pediatr Infect Dis J. 2000, 19: 1148-1153.CrossRefPubMed
Metadata
Title
Impact of long-term viral suppression in CD4+ recovery of HIV-children on Highly Active Antiretroviral Therapy
Authors
Salvador Resino
Rosa Resino
Juan A Leon
José M Bellon
Pablo Martin-Fontelos
Jose T Ramos
Dolores Gurbindo-Gutierrez
Maria I de Jose
Luis Ciria
Maria A Muñoz-Fernandez
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2006
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-6-10

Other articles of this Issue 1/2006

BMC Infectious Diseases 1/2006 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.