Cargando…

Effects of recombinant human growth hormone on HIV-1-specific T-cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up

BACKGROUND: Efficacious immune-based therapy in treated chronic HIV-1 infection requires the induction of virus-specific CD4(+ )T cells and subsequent maturation and maintenance of specific memory CD8(+ )T cells. Concomitant daily administration of recombinant human growth hormone (rhGH) with highly...

Descripción completa

Detalles Bibliográficos
Autores principales: Herasimtschuk, Anna A, Westrop, Samantha J, Moyle, Graeme J, Downey, Jocelyn S, Imami, Nesrina
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613878/
https://www.ncbi.nlm.nih.gov/pubmed/18976455
http://dx.doi.org/10.1186/1476-8518-6-7
_version_ 1782163202901016576
author Herasimtschuk, Anna A
Westrop, Samantha J
Moyle, Graeme J
Downey, Jocelyn S
Imami, Nesrina
author_facet Herasimtschuk, Anna A
Westrop, Samantha J
Moyle, Graeme J
Downey, Jocelyn S
Imami, Nesrina
author_sort Herasimtschuk, Anna A
collection PubMed
description BACKGROUND: Efficacious immune-based therapy in treated chronic HIV-1 infection requires the induction of virus-specific CD4(+ )T cells and subsequent maturation and maintenance of specific memory CD8(+ )T cells. Concomitant daily administration of recombinant human growth hormone (rhGH) with highly active antiretroviral therapy (HAART) was used in chronically infected patients with lipodystrophy in an attempt to reconstitute these virus-specific T-cell responses. METHODS: Individuals with chronic HIV-1 infection on HAART were enrolled on a randomized, double-blinded, placebo-controlled study to receive rhGH therapy. We assessed HIV-1-specific proliferative CD4(+ )and interferon-gamma (IFN-γ)-producing CD8(+ )T-cell responses, quantified thymic output and proviral HIV-1 DNA at the following time points: baseline; after 12 weeks of rhGH therapy; at 24 weeks, after randomization into three groups [placebo weeks 12–24 (Group A), alternate-day dosing weeks 12–24 (Group B), and twice-per-week dosing weeks 12–24 (Group C)]; and at 48 weeks after all patients had received HAART alone for the final 24 weeks. RESULTS: We found significant increases in both proliferative CD4(+ )and IFN-γ-producing CD8(+ )HIV-1-specific T-cell responses after daily administration of rhGH. This increase was focused on HIV-1 Gag-specific T-cell responses. Following subsequent randomisation into different dosing regimens, HIV-1-specific proliferative CD4(+ )T-cell responses declined in patients receiving less frequent dosing of rhGH, while virus-specific IFN-γ-producing CD8(+ )T-cell responses were maintained for longer periods of time. There was no significant change in thymic output and the cell-associated HIV-1 DNA remained stable in most patients. An increased anti-HIV-1 Nef-specific CD4(+ )T-cell proliferative response was correlated to a decrease in proviral load, and an increased HIV-1 Gag-specific IFN-γ-producing CD8(+ )T-cell response correlated with an increase in proviral load. CONCLUSION: The implication of these data is that daily dosing of rhGH with HAART, in addition to improving HIV-1-associated lipodystrophy, may reverse some of the T-lymphocyte dysfunction seen in most treated HIV-1-positive patients, in a dose-dependent manner. Such immune-based therapeutic strategies used in treated, chronic HIV-1 infection may enable the induction of virus-specific CD4(+ )T cells essential for the subsequent 'kick-start' and expansion of virus-specific CD8(+ )T cells. TRIAL REGISTRATION: GH in Lipoatrophy IMP22350.
format Text
id pubmed-2613878
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-26138782009-01-06 Effects of recombinant human growth hormone on HIV-1-specific T-cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up Herasimtschuk, Anna A Westrop, Samantha J Moyle, Graeme J Downey, Jocelyn S Imami, Nesrina J Immune Based Ther Vaccines Original Research BACKGROUND: Efficacious immune-based therapy in treated chronic HIV-1 infection requires the induction of virus-specific CD4(+ )T cells and subsequent maturation and maintenance of specific memory CD8(+ )T cells. Concomitant daily administration of recombinant human growth hormone (rhGH) with highly active antiretroviral therapy (HAART) was used in chronically infected patients with lipodystrophy in an attempt to reconstitute these virus-specific T-cell responses. METHODS: Individuals with chronic HIV-1 infection on HAART were enrolled on a randomized, double-blinded, placebo-controlled study to receive rhGH therapy. We assessed HIV-1-specific proliferative CD4(+ )and interferon-gamma (IFN-γ)-producing CD8(+ )T-cell responses, quantified thymic output and proviral HIV-1 DNA at the following time points: baseline; after 12 weeks of rhGH therapy; at 24 weeks, after randomization into three groups [placebo weeks 12–24 (Group A), alternate-day dosing weeks 12–24 (Group B), and twice-per-week dosing weeks 12–24 (Group C)]; and at 48 weeks after all patients had received HAART alone for the final 24 weeks. RESULTS: We found significant increases in both proliferative CD4(+ )and IFN-γ-producing CD8(+ )HIV-1-specific T-cell responses after daily administration of rhGH. This increase was focused on HIV-1 Gag-specific T-cell responses. Following subsequent randomisation into different dosing regimens, HIV-1-specific proliferative CD4(+ )T-cell responses declined in patients receiving less frequent dosing of rhGH, while virus-specific IFN-γ-producing CD8(+ )T-cell responses were maintained for longer periods of time. There was no significant change in thymic output and the cell-associated HIV-1 DNA remained stable in most patients. An increased anti-HIV-1 Nef-specific CD4(+ )T-cell proliferative response was correlated to a decrease in proviral load, and an increased HIV-1 Gag-specific IFN-γ-producing CD8(+ )T-cell response correlated with an increase in proviral load. CONCLUSION: The implication of these data is that daily dosing of rhGH with HAART, in addition to improving HIV-1-associated lipodystrophy, may reverse some of the T-lymphocyte dysfunction seen in most treated HIV-1-positive patients, in a dose-dependent manner. Such immune-based therapeutic strategies used in treated, chronic HIV-1 infection may enable the induction of virus-specific CD4(+ )T cells essential for the subsequent 'kick-start' and expansion of virus-specific CD8(+ )T cells. TRIAL REGISTRATION: GH in Lipoatrophy IMP22350. BioMed Central 2008-10-31 /pmc/articles/PMC2613878/ /pubmed/18976455 http://dx.doi.org/10.1186/1476-8518-6-7 Text en Copyright © 2008 Herasimtschuk et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Herasimtschuk, Anna A
Westrop, Samantha J
Moyle, Graeme J
Downey, Jocelyn S
Imami, Nesrina
Effects of recombinant human growth hormone on HIV-1-specific T-cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up
title Effects of recombinant human growth hormone on HIV-1-specific T-cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up
title_full Effects of recombinant human growth hormone on HIV-1-specific T-cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up
title_fullStr Effects of recombinant human growth hormone on HIV-1-specific T-cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up
title_full_unstemmed Effects of recombinant human growth hormone on HIV-1-specific T-cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up
title_short Effects of recombinant human growth hormone on HIV-1-specific T-cell responses, thymic output and proviral DNA in patients on HAART: 48-week follow-up
title_sort effects of recombinant human growth hormone on hiv-1-specific t-cell responses, thymic output and proviral dna in patients on haart: 48-week follow-up
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2613878/
https://www.ncbi.nlm.nih.gov/pubmed/18976455
http://dx.doi.org/10.1186/1476-8518-6-7
work_keys_str_mv AT herasimtschukannaa effectsofrecombinanthumangrowthhormoneonhiv1specifictcellresponsesthymicoutputandproviraldnainpatientsonhaart48weekfollowup
AT westropsamanthaj effectsofrecombinanthumangrowthhormoneonhiv1specifictcellresponsesthymicoutputandproviraldnainpatientsonhaart48weekfollowup
AT moylegraemej effectsofrecombinanthumangrowthhormoneonhiv1specifictcellresponsesthymicoutputandproviraldnainpatientsonhaart48weekfollowup
AT downeyjocelyns effectsofrecombinanthumangrowthhormoneonhiv1specifictcellresponsesthymicoutputandproviraldnainpatientsonhaart48weekfollowup
AT imaminesrina effectsofrecombinanthumangrowthhormoneonhiv1specifictcellresponsesthymicoutputandproviraldnainpatientsonhaart48weekfollowup