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Abstract
Recombinant Growth Hormone Induces HIV-1-Specific CD4 and CD8 T-Cell Responses in Patients on Effective Antiretroviral Therapy
Imami N.1, Moyle G.2, Gazzard B.2, Gotch F.1
Introduction: Immunotherapeutic strategies in treated chronic HIV-1 infection should enable induction of virus-specific CD4+ T cells and subsequent activation and maintenance of specific memory CD8+ T cells. Recombinant human growth hormone (rhGH) therapy was administered concomitantly with effective antiretroviral therapy (ART) in chronically infected patients in an attempt to reconstitute HIV-1-specific CD4 and CD8 T cell responses.
Methods: Individuals with chronic HIV-1 infection on effective ART (VL BDL, CD4 >200 cells/ul) received rhGH therapy (4mg/day subcutaneously) for 12 weeks, after which patients were randomised into three groups - group 1 (placebo weeks 12-24); group 2 (alternate-day dosing weeks 12-24); and group 3 (twice-per-week dosing weeks 12-24). All patients received ART alone from weeks 24-48. HIV-1-specific proliferative CD4 T cell responses, interferon (IFN)-g-producing CD8 T-cell responses, and proviral HIV-1 DNA levels were quantified at baseline; 12 weeks; 24 weeks; and 48 weeks.
Results: We found significant increases in both proliferative CD4 (evaluated with both recombinant and whole-HIV-1 antigen) and IFN-g-producing CD8 (evaluated with both rVV and peptide pools) HIV-1-specific T-cell responses after daily administrations of rhGH. Following randomisation to different dosing regimens, HIV-1-specific proliferative CD4 T-cell responses declined in those receiving less frequent dosing of rhGH, while virus-specific IFN-g-producing CD8 T-cell responses were maintained for longer periods of time. Whilst viral load, CD4 and CD8 T cell counts remained unchanged, there was significant enhancement in T-cell maturation and differentiation. Cell-associated HIV-1 DNA was stable in most patients.
Conclusions: The implication of these data is that concomitant administration of rhGH with effective ART results in a dose-dependent reversal of both the CD4 and the CD8 T lymphocyte dysfunction commonly observed in HIV-1-positive patients. Such immune-based therapeutic strategies 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 specific CD8 T cells.
The 3rd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
WePe16.7B01
Suggested Citation
"ImamiN., et al.
Recombinant Growth Hormone Induces HIV-1-Specific CD4 and CD8 T-Cell Responses in Patients on Effective Antiretroviral Therapy.
Poster Exhibition:
The 3rd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
WePe16.7B01"
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