This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Highly active anti-retroviral therapy (HAART) has dramatically influenced the AIDS epidemic in developed countries. HAART treatment suppresses HIV replication, thereby preventing further immune destruction. However, many patients have limited immune recovery due to the immune degradation imparted from the direct and indirect effects of the previously untreated chronic viral infection. We hypothesize that an effective immune therapy provided concurrently with HAART will result in a more functionally complete immune recovery and a better prognosis for HIV+ patients. IL-7 is unique among other immune therapeutic candidates in that it has the ability to impact T-cell renewal in the periphery as well as thymocyte maturation and T-cell production in the thymus. We will treat SIV+ macaques with HAART alone or HAART with IL-7 to evaluate the ability of IL-7 to influence immune reconstitution during the acute as well as during the chronic phase of the infection.
Aim 1 will assess the effect of IL-7 on T-cell phenotypes, proliferation and thymic production in HAART-treated SIV infected macaques.
Aim 2 will evaluate any potentially negative effects of the IL-7 therapy through an assessment of viral replication and cell types infected.
Aim 3 will determine if IL-7 administration increases the levels of SIV-specific T cells and improves clinical outcome after cessation of HAART. We anticipate that use of the SIV/macaque model will assist in the approval of IL-7 as an immune therapeutic for HIV-infected patients as well as identify the patient populations most likely to benefit from this therapy.
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