Low‐dose growth hormone for 40 weeks induces HIV ‐1‐specific T cell responses in patients on effective combination anti‐retroviral therapy

Summary Recombinant human growth hormone (rh GH ) administered to combination anti‐retroviral therapy (c ART )‐treated human immunodeficiency virus‐1 ( HIV ‐1)‐infected individuals has been found to reverse thymic involution, increase total and naive CD 4 T cell counts and reduce the expression of activation and apoptosis markers. To date, such studies have used high, pharmacological doses of rh GH . In this substudy, samples from treated HIV ‐1 + subjects, randomized to receive either a physiological dose (0·7 mg) of rh GH ( n  = 21) or placebo ( n  = 15) daily for 40 weeks, were assessed. Peptide‐based enzyme‐linked immunospot ( ELISPOT ) assays were used to enumerate HIV ‐1‐specific interferon ( IFN) ‐γ‐producing T cells at baseline and week 40. Individuals who received rh GH demonstrated increased responses to HIV ‐1 G ag overlapping 20mer and G ag 9mer peptide pools at week 40 compared to baseline, whereas subjects who received placebo showed no functional changes. Subjects with the most robust responses in the ELISPOT assays had improved thymic function following rh GH administration, as determined using CD 4 + T cell receptor rearrangement excision circle ( T REC ) and thymic density data from the original study. T cells from these robust responders were characterized further phenotypically, and showed decreased expression of activation and apoptosis markers at week 40 compared to baseline. Furthermore, CD 4 and CD 8 T cell populations were found to be shifted towards an effector and central memory phenotype, respectively. Here we report that administration of low‐dose rh GH over 40 weeks with effective c ART resulted in greater improvement of T lymphocyte function than observed with c ART alone, and provide further evidence that such an approach could also reduce levels of immune activation.