Dissecting the influence of HIV infection and treatment with antiretroviral therapy on Human Papillomavirus infection, disease and immunity: Designing new tools for therapeutic intervention.

• Applicant: Dr. Christof Geldmacher
• Subject Area: Virology ; Immunology ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2015 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 270691494

• Final Report Year: 2024

Final Report Abstract

The increase of HPV infection associated cervical lesions and accelerated carcinogenesis in HIV+ women of antiretroviral therapy (ART) implies that HIV-induced dysregulation of the HPV-specific immune response increases HR HPV replication, reduces HPV clearance and consequently increases the risk of progression to mild and moderate dysplasia even in the presence of ART. We postulate that higher HR HPV loads in HIV+ women in the presence of moderate cervical dysplasia facilitate statistically more frequent HPV DNA integration events into the host genome. We hypothesize that HPV viral integration is the key event in driving rapid cancerogenesis in HIV+ women. A therapeutic HPV vaccine might be able to resurrect HPV-specific adaptive immunity to erradicate persistent HPV infection and hence prevent HPV disease progression in HIV+ individuals on ART. The 2H study aims to elucidate the complicated interplay between HIV, the immune system and HPV induced carcinogenesis in the era of ART.

Publications

• 30th National Institute of Medical Research (NIMR)- Annual Scientific Conference in Arusha 2016, "The 2H study in Mbeya from April 2013 to June 2016". This presentation was the overall winner 2016 of the Mount Kilimanjaro Scientific Award.
  Ruby Mcharo
  
• Conference on Retroviruses and Opportunistic Infections (CROI) in Boston 2016, " High Prevalence of HR-HPV Infection in HIV-Infected Women From Tanzania".
  Arne Kroidl
  
• "Distribution of Human papilloma virus (HPV) among women enrolled in cervical cancer study in Mbeya- Tanzania". This presentation was awarded 1st Prize for best poster presentation (HIV and Global Health track).
  Jonathan Mnkai
  
• 7th Symposium Infectious Diseases in Africa (IDA) in Cape Town, 2017, "Dissecting the influence of HIV infection and treatment with ART on HPV infection, disease and immunity" This presentation was awarded with 1st price for best oral presentation.
  Wilbert Mbuya
  
• 7th Symposium Infectious Diseases in Africa (IDA) in Cape Town, 2017, "Phenotyping mucosal T-Cells in HIV- and HIV+ women with/without pre-cancerous cervical lesions/invasive cancer in Mbeya - Tanzania".
  Jacklina Mhidze
  
• Depletion and activation of mucosal CD4 T cells in HIV infected women with HPV-associated lesions of the cervix uteri. PLOS ONE, 15(10), e0240154.
  Mbuya, Wilbert; Mcharo, Ruby; Mhizde, Jacklina; Mnkai, Jonathan; Mahenge, Anifrid; Mwakatima, Maria; Mwalongo, Wolfram; Chiwerengo, Nhamo; Hölscher, Michael; Lennemann, Tessa; Saathoff, Elmar; Rwegoshora, France; Torres, Liset; Kroidl, Arne; Geldmacher, Christof; Held, Kathrin & Chachage, Mkunde
  
• Depletion of Human Papilloma Virus E6- and E7-Oncoprotein-Specific T-Cell Responses in Women Living With HIV. Frontiers in Immunology, 12.
  Mbuya, Wilbert; Held, Kathrin; Mcharo, Ruby D.; Haule, Antelmo; Mhizde, Jacklina; Mnkai, Jonathan; Mahenge, Anifrid; Mwakatima, Maria; Sembo, Margareth; Mwalongo, Wolfram; Agrea, Peter; Hoelscher, Michael; Maboko, Leonard; Saathoff, Elmar; Geisenberger, Otto; Rwegoshora, France; Torres, Liset; Koup, Richard A.; Kroidl, Arne ... & Geldmacher, Christof
  
• HPV Type Distribution in HIV Positive and Negative Women With or Without Cervical Dysplasia or Cancer in East Africa. Frontiers in Oncology, 11.
  Mcharo, Ruby; Lennemann, Tessa; France, John; Torres, Liseth; Garí, Mercè; Mbuya, Wilbert; Mwalongo, Wolfram; Mahenge, Anifrid; Bauer, Asli; Mnkai, Jonathan; Glasmeyer, Laura; Judick, Mona; Paul, Matilda; Schroeder, Nicolas; Msomba, Bareke; Sembo, Magreth; Chiwerengo, Nhamo; Hoelscher, Michael; Geisenberger, Otto ... & Geldmacher, Christof
  
• Eurogin in Düsseldorf, 2022, “HPV Type Distribution in HIV Positive and Negative Women With or Without Cervical Dysplasia or Cancer South West Tanzania”
  Christof Geldmacher
  
• European Congress on Gynecological Oncology in Berlin, 2022, “MULTIPLEXED BIOMARKER DETECTION USING THE QUANTIGENE ASSAY IN WOMEN LIVING WITH HIV FOR CERVICAL DYSPLASIA DETECTION”
  Anna Sophie Skof
  
• High-risk human papillomavirus genotype distribution among women living with and at risk for HIV in Africa. AIDS, 37(4), 625-635.
  Chachage, Mkunde; Parikh, Ajay P.; Mahenge, Anifrid; Bahemana, Emmanuel; Mnkai, Jonathan; Mbuya, Wilbert; Mcharo, Ruby; Maganga, Lucas; Mwamwaja, Jaqueline; Gervas, Reginald; Kibuuka, Hannah; Maswai, Jonah; Singoei, Valentine; Iroezindu, Michael; Fasina, Abiola; Esber, Allahna; Dear, Nicole; Imbach, Michelle; Crowell, Trevor A. ... & Geldmacher, Christof
  
• Long-term follow-up on HIV infected and non-infected women with cervical cancer from Tanzania: staging, access to cancer-directed therapies and associated survival in a real-life remote setting. BMC Cancer, 22(1).
  Glasmeyer, Laura; Mcharo, Ruby Doryn; Torres, Liset; Lennemann, Tessa; Danstan, Elizabeth; Mwinuka, Nice; Judick, Mona; Mueller, William; Mbuya, Wilbert; Hölscher, Michael; Lellé, Ralph; Geldmacher, Christof; Kroidl, Arne & France, John Rwegoshora
  
• 35th IPVC conference in Washington DC, 2023, ”HPV Type Distribution in HIV Positive and Negative Women With or Without Cervical Dysplasia or Cancer South West Tanzania” This presentation was awarded with a IPVC 2023 Travel Scholarship
  Wilbert Mbuya
  
• Therapeutic Efficacy of a VSV-GP-based Human Papilloma Virus Vaccine in a Murine Cancer Model. Journal of Molecular Biology, 435(13), 168096.
  Riepler, Lydia; Frommelt, Laura-Sophie; Wilmschen-Tober, Sarah; Mbuya, Wilbert; Held, Kathrin; Volland, André; von Laer, Dorothee; Geldmacher, Christof & Kimpel, Janine
  
• 36th IPVC conference in Edinburgh, 2024, “DISSECTING THE IMPACT OF HIV ON HPV-SPECIFIC IMMUNITY, VIRAL PERSISTENCE AND MOLECULAR SIGNATURES OF CERVICAL DYSPLASIA”
  Wilbert Mbuya
  
• NIMR conference in 2024, “Quantification of cervical cancer causing HPV16 E6 and E7 oncogene-transcripts in women living with and without HIV in Mbeya, Tanzania.”
  Wilbert Mbuya