Induction and Expansion of T Cell Repertoire Using Growth Hormone and Vaccination in HIV-1 Infected Patients

• The rhGH activates the thymic function. [ Time Frame: from one year post rhGH administration ] [ Designated as safety issue: Yes ]
• This effect is lasting once the rhGH administration is interrupted. [ Time Frame: from at least one year since the last rhGH administration ] [ Designated as safety issue: Yes ]

• The rhGH activates the thymic function.
• The effect of the rhGh can be expanded by vaccine immunization.
• This effect is lasting once the rhGH administration is interrupted.

Concomitant administration of recombinant human growth hormone (rhGH) may boost the expansion of immune reconstitution and broaden specific T cell responses not achievable by vaccination alone. The main objective of that study is to test the validity of this hypothesis with vaccines which are routinely administered to HIV-1 patients(tetanus toxoid and hepatitis A virus vaccines) in order to, if proven of value, use this strategy of HIV vaccination in the near future. This is a pilot, randomized, clinical open label study aimed to investigate thymic functionality and the HIV-specific responses after administration of rhGH in HIV-1 infected patients in highly active antiretroviral therapy (HAART) regimen.

The purpose of a therapeutic vaccine is to control, induce and expand humoral and cellular immune responses capable to control HIV infection. The administration of a conventional vaccine results in the expansion of peripheral clones. Concomitant administration of rhGH may boost this expansion and reconstitute specific T cell responses not achievable by vaccination alone. In this study we want to investigate whether the administration of rhGH expand T cell repertoire and whether there is an increase in the specific cellular responses to HIV-1 and recall antigens and, lately, whether this responses can be further amplified after immunization with tetanus toxoid and hepatitis A vaccines. This Hypothesis will be evaluated by the measurement of thymic volume, the expansion of naïve, memory and effector cell subsets, analysis of thymic emigrants (TRECs) before, during and after rhGH administration and vaccination. Moreover, T cell receptor rearrangement, specific antibodies and cellular responses to antigenic peptides will be determined.

• Biological: recombinant human Growth Hormone
  Growth Hormone during 6 months (30UG/KG/DAY)
• Biological: Vaccination
  Vaccination (Hepatitis A+B + tetanus toxoid) at week 16
• Drug: HAART
  HAART all over the trial

• Experimental: A
  growth hormone + vaccination + HAART
  Interventions:

  • Biological: recombinant human Growth Hormone
  • Biological: Vaccination
  • Drug: HAART
• Experimental: B
  growth hormone + HAART
  Interventions:

  • Biological: recombinant human Growth Hormone
  • Drug: HAART
• Experimental: C
  vaccination + HAART
  Interventions:

  • Biological: Vaccination
  • Drug: HAART
• Active Comparator: D
  control healthy HIV negative + vaccination
  Intervention: Biological: Vaccination

Inclusion Criteria:

1. HIV-1 asymptomatic patients in HAART regimen (> 6 months)
2. Viral load < 50 copies/ml
3. Number CD4 cells > 250 cells/mm3
4. Non responders to vaccination (tetanus toxoid and/or Hepatitis A virus)
5. Well-disposition to rhGh daily administration (6 months of treatment)

Exclusion Criteria:

1. AIDS outbreak
2. Allergy or hyperreactivity to rhGH or vaccines
3. Diabetes Mellitus
4. Renal, hepatic, pancreatic disorders
5. Chronic diseases
6. Dementia
7. Pregnancy

• Hospital Clinic of Barcelona
• Hospital General Universitario Gregorio Marañon
• Carlos III Health Institute