Plasma and cellular immune biomarkers of Kaposi's sarcoma in HIV-1 suppressed patients

PROJECT SUMMARY/ABSTRACT Successful ART coverage has has reduced AIDS-related mortality from 2.2 million in mid 2000s to 1.8 million in 2019. In turn, this has led to global increase in life expectancy of PLWH. In the US, it is estimated that 50% of the PLWH are older than 50-years and accounts for 70% of total deaths among PLWH. The

ageing population of PLWH is now facing an increase in age-related non-communicable diseases like cancers. However, in sub-Saharan Africa (SSA) where ~66% of global 38.4 million PLWH reside, data on the changing demographics of the HIV pandemic are scarce. Although it is expected that non-HIV- associated malignancies (HIVAM) to increase and at an earlier age at diagnosis as a consequence of

ageing among PLWH, there is limited data on the impact of HIV and ageing on cancer development in SSA. The limited data on the impact of ageing on health and the nature of the accelerated ageing process in PLWH in SSA could be partly due to the fact that, 1) prior to ART scale up in Africa, most PLWH were

not treated with ART and died at an earlier age, rarely lived beyond 50-years of age. It is only through ART a new generation of PLWH are now ageing in SSA. 2) Importantly, in the past, most of the training opportunities in SSA focused on the training of clinicians to address patient care with minimal emphasis on

research training. Coupled with limited research training opportunities, particularly in HIV and ageing, this has led to low research output in SSA. To address this gap of well-trained HIV researchers, we are proposing to recruit and mentor an early-stage female investigator (Dr. Herrieth) on the basics of HIV

research through academic instruction and conducting a hands-on research training to determine the incidence, trends, and outcome of non-HIVAM in ageing PLWH in Tanzania. The overall objective is to train the already identified young, enthusiastic female early-stage investigator on expansion of the K43 dataset

to include other cancers in order to determine incidence, trends, and outcomes of non-HIVAM in Tanzania. We hypothesize that while successful ART improves lifespan of PLWH, but it also lead to an increase in incidence of non-HIVAM, at an earlier chronological age at cancer diagnosis due to HIV associated chronic

inflammation and unwanted effects of ART. We will utilize the parent K43 study infrastructure to integrate, and train the early-stage investigator on how to a) design tools for secondary data curation, and b) perform data analysis to determine incidence, trend, and outcome of non-HIVAM among ageing PLWH. This

training is significant as it provides a unique opportunity for the trainee to acquire skills in HIV and ageing research. Moreover, the study will foster gender inclusion and diversity in research, motivate others, and improve the multidisciplinary research workforce. Overall, these efforts will generate preliminary data for

future studies to understand the impact of HIV and ageing to improve health outcomes for PLWH in SSA.