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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Double Strategy to Induce and Expand the T Cell Repertoire by the Administration of Growth Hormone and Vaccination in HIV-1 Infected Patients

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: recombinant human Growth Hormone
* Biological: Vaccination
* Drug: HAART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 asymptomatic patients in HAART regimen (> 6 months) Viral load < 50 copies/ml Number CD4 cells > 250 cells/mm3 Non responders to vaccination (tetanus toxoid and/or Hepatitis A virus) Well-disposition to rhGh daily administration (6 months of treatment) Exclusion Criteria: AIDS outbreak Allergy or hyperreactivity to rhGH or vaccines Diabetes Mellitus Renal, hepatic, pancreatic disorders Chronic diseases Dementia Pregnancy

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>growth hormone + vaccination + HAART | Biological: recombinant human Growth Hormone<br>* Growth Hormone during 6 months (30UG/KG/DAY)<br>Biological: Vaccination<br>* Vaccination (Hepatitis A+B + tetanus toxoid) at week 16<br>Drug: HAART<br>* HAART all over the trial<br>|
| Experimental: B<br>growth hormone + HAART | Biological: recombinant human Growth Hormone<br>* Growth Hormone during 6 months (30UG/KG/DAY)<br>Drug: HAART<br>* HAART all over the trial<br>|
| Experimental: C<br>vaccination + HAART | Biological: Vaccination<br>* Vaccination (Hepatitis A+B + tetanus toxoid) at week 16<br>Drug: HAART<br>* HAART all over the trial<br>|
| Active Comparator: D<br>control healthy HIV negative + vaccination | Biological: Vaccination<br>* Vaccination (Hepatitis A+B + tetanus toxoid) at week 16<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients HIV+ that recover the immunospecific responses against tetanus toxoid and Hepatitis A at 24 weeks of rhGH administration (time of treatment interruption). |  | from 24 weeks post rhGH administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rhGH activates the thymic function. |  | from one year post rhGH administration | 
| This effect is lasting once the rhGH administration is interrupted. |  | from at least one year since the last rhGH administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth Hormone, HIV-1, Vaccination, Thymopoiesis, HIV-specific responses, Treatment Experienced