15th Annual Conference of the British HIV Association 1-3 April 2009, Liverpool, UK

IMPACT OF RECOMBINANT HUMAN GROWTH HORMONE ON T-CELL PHENOTYPE AND FUNCTION IN VITRO AND IN VIVO DURING TREATED HIV-1 INFECTION

HIV Med 2009 Apr 1-3 (Suppl 1);15:9 (abstract no. O17)

A Herasimtschuk¹, M Nelson², G Moyle², M Bower² and N Imami^1
1Department of Immunology, Imperial College London, London, UK, ²Chelsea and Westminster Hospital, London, UK

BACKGROUND: HIV-1-immune-based therapy seeks to reconstitute specific CD4+ and CD8+ T-cell responses. To this end, we administered recombinant human growth hormone (rhGH) daily in addition to highly active antiretroviral therapy (HAART) in chronically infected HIV-1+ individuals, and further determined the in vitro effects of rhGH on T-cell phenotype and function.

METHODS: Peripheral blood mononuclear cells from HIV-1 infected individuals and healthy controls were cultured with rhGH for 72 hours. Phenotypic analysis of CD4+ and CD8+ T cells was carried out before and after culture. Patients enrolled on a double-blinded, placebo-controlled study received daily rhGH. We assessed HIV-1 specific proliferative CD4+ and interferon-gamma (IFN-γ) producing CD8+ T-cell responses, quantified thymic output and proviral DNA at baseline, after 12 weeks rhGH therapy, at 24 and 48 weeks.

RESULTS: Following culture with rhGH, there was a significant decrease in the expression of the activation marker HLA-DR on CD4+ (P=0.01) and CD8+ (P=0.006) T cells and the expression of the exhaustion marker PD1 in the naïve CD8+ T-cell population (P=0.03) in HIV-1+ individuals. Patients in the study demonstrated 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 and these responses declined with less frequent dosing. There was no change in thymic output and pro-viral DNA remained stable.

CONCLUSIONS: These data indicate that beneficial effects of rhGH on T cells in the periphery correlate with reduced activation and exhaustion markers. Daily dosing of rhGH with HAART may reverse some of the T-lymphocyte dysfunction seen in most treated HIV-1+ patients. Thus, immune-based therapeutic approaches may enable the induction of HIV-1 specific CD4+ T cells required to revive the expansion of virus-specific CD8+ T cells.

2009-04-01
O17

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