Background:  Immunotherapeutic strategies in treated chronic HIV-1 infection require induction of virus-specific CD4 T cells and subsequent activation and maintenance of specific memory CD8 T cells. Concomitant daily administration of recombinant human growth hormone (rhGH) therapy with effective ART was used in chronically infected patients in an attempt to reconstitute HIV-1-specific CD4 and CD8 T-cell responses.

Methods:  We enrolled in this randomized, double-blind, placebo-controlled study, 12 individuals with chronic HIV-1 infection on effective ART (viral load below detectable levels, CD4 >200 cells/mL) to receive rhGH therapy (4 mg/day subcutaneously). We assessed HIV-1-specific proliferative CD4 and interferon (IFN)-g-producing CD8 T cell responses, T-cell receptor recombination (TREC) levels and quantified proviral HIV-1 DNA:  at baseline; after 12 weeks of rhGH therapy; at 24 weeks after randomization into 3 groups—placebo weeks 12 to 24 (Group 1), alternate-day dosing weeks 12 to 24 (Group 2), and twice-per-week dosing weeks 12 to 24 (Group 3)]— and at 48 weeks after all patients had received ART alone for the final 24 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 subsequent randomization 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. While viral load and CD4 and CD8 T cell counts remained unchanged, T cell maturation and differentiation were significantly enhanced. TREC levels and cell-associated HIV-1 DNA were 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⁺ 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.