Dissecting the influence of HIV infection and treatment with antiretroviral therapy on Human Papillomavirus infection, disease and immunity - Identifying possible targets for therapeutic intervention

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The increase in Human Papilloma Virus (HPV) associated cervical cancer in HIV+ women implies that defects in the HPV-specific CD4 T cell response play an important role in pathogenesis. It can thus be hypothesized that depletion and dysfunction of HPV-specific T cell and antibody responses after HIV infection and even after initiation of highly active antiretroviral therapy (HAART) contribute to frequent HPV reinfection, increased diversity and persistence of High Risk (HR) HPV types finally leading to malignant cell transformation. We postulate that a therapeutic HPV vaccine consisting of selected antigenic targets can specifically prime and reconstitute HPV-specific adaptive immunity to prevent HPV disease progression in HIV+ individuals on HAART. The proposed study aims to elucidate the complicated interplay between HIV, the immune system and HPV induced carcinogenesis in the era of HAART, HPV antigenic regions frequently recognized by the HPV-specific T cell response will be mapped in immunocompetent women and will provide the basis for rationale design of a vaccine tailored for the HR HPV types most frequently occurring in HIV+ subjects. During a later stage, a side study, which will seek additional ethical approval, is planned to explore the safety and immunogenicity of a TFDA* approved subunit vaccine (Gardasil™) or a HPV16 peptide-based vaccine (ISA Pharmaceuticals) in healthy HIV+ women on HAART