The role of natural immunity in delaying of HIV progression from infection to AIDS/death among children in Uganda and Botswana

Samuel Kyobe is a medical doctor currently pursuing his Ph.D. in Medicine (Human Genetics) at Makerere University. His Ph.D. focuses on the role of molecules on the white blood cells (human leucocyte antigens, HLA) that present HIV particles to the immune system for destruction and clearance of cells infected by HIV. Samuel graduated with a Bachelor of Medicine and Bachelor of Surgery from Makerere University, followed by an Internship for one year at Rubaga Hospital. From Rubaga Hospital, Samuel returned to Makerere University College of Health Sciences (MakCHS) in 2011 to pursue his dream in Biomedical research, first graduating with a Masters of Medicine in Medical Microbiology in 2016 and subsequently offered a tenured position of Assistant Lecturer and later promoted to Lecturer in 2017.

Samuel has been part of various research activities and infrastructure developments at MakCHS, such as the Collaborative African Genetics Network, H3Africa Biorepository, and B3Africa international research collaborations. He also led the effort for the setup and construction of the University’s first and largest Biorepository at Makerere University. These research efforts provided a firm foundation for his enrollment into the Ph.D. program, winning a Ph.D. Fellowship in 2017 with MUIIplus (Makerere University/UVRI Center of Excellence in Infection and Immunity) to explore the role of HLA class I molecules in the progression of HIV from infection to disease in children from Uganda and Botswana. Samuel is supervised by Prof. Graeme Mardon of Baylor College of Medicine, an esteemed researcher in human genetics, and Dr. Jacqueline Kyosiimire-Lugemwa, an accomplished HIV/AIDS researcher based at Uganda Virus Research Institute, Entebbe. Samuel has also received tremendous academic support from Prof. Neil Hanchard now at NIH, Bethesda USA, who is a member of the doctoral committee. Samuel’s research interests span various interdisciplinary fields of human genetics, immunology, bioinformatics, clinical epidemiology and medical microbiology, which are intricately interwoven in his Ph.D. studies.

Why should people care about your research?

HIV/AIDS is still a significant public health concern in Africa, where 26 million people are infected. Despite the programs such as preventing mother-to-child transmission of HIV, more than 220,000 children are born with HIV annually, and 110,000 die due to HIV-related complications. Therefore, safe and effective HIV vaccines and therapeutics are urgently required. Samuel’s research investigates the role of natural immunity in the prevention of HIV progression from infection to AIDS/death. This research focuses on a rare (about 1-5%) group of children infected with HIV perinatally but do not develop AIDS or die from HIV-related causes and are not on antiretroviral therapy (ART) for ten years or more of life. “We presuppose that this rare group of children can naturally control HIV infection, providing some leads for new HIV therapies and vaccine strategies. Unfortunately, (on a very selfish note) with the recent changes in ART policies globally (Test and Treat), we shall never see this rare group of children again, making this research quite important.” Samuel noted. This comes across as the final opportunity to find answers from how the body naturally deals with HIV on infection, a generational opportunity. Furthermore, such research has not been previously conducted in African populations both at the scale and approach we are using in this study.

What are the significant challenges in your research area?

HIV research is a rapidly evolving field and incremental gains of HIV research to clinical solutions such as vaccines seems to be slow; this Samuel is comparing to the recent Coronavirus epidemic, which has seen the fastest rate of vaccine development for a disease of global concern. “In genetics research like the one I am conducting; large numbers of subjects are needed to observe scientific evidence; this makes HIV genetics research expensive.” said Samuel. Fortunately, with recent advances in bioinformatics, including tools to interrogate genetic data, we can now take advantage of available genetic data (e.g., whole genome, whole exome, and chip datasets) to conduct genetics studies of the HLA region at the scale we have in this study. Samuel happens to be among the first cohort of students studying in the area of bioinformatics in MakCHS, looking at a nascent field there are challenges of limited peer support. You rely more on self-directed and experiential learning, which is quite resourceful and a great experience. One future challenge is validating our findings; with the changes in ART policies, we do not have the cohorts to replicate our results.

How will this research help you achieve your long-term career plans?

Samuel believes this is a springboard for his long-term career goals. “What I like the most is studying a breadth of subjects in one PhD program, including human genetics, immunology, bioinformatics, and clinical epidemiology. I believe I have acquired or accumulated the necessary skills and knowledge to further my long-term career goals in these subjects,” noted Samuel. One of the significant outputs of his research is the publication of findings, which he considers an essential primer for future grant applications especially in the area of expertise. In addition, I have had the opportunity to work with international scientists/researchers in Baylor College of Medicine, Texas and a year-long laboratory rotation in the University of California, Berkeley. These opportunities have exposed me to state-of-the-art technologies barely available here in Uganda, which open my thinking horizons on how much more I can achieve with simple ideas.

What are some of the findings you are seeing from your research?

Samuel has some interesting findings on the role of HLA class I molecules in pediatric HIV progression. In addition to what is typically termed canonical HLA molecules (HLA-B*57:03 and B*58:01), together with others, found that a previously unreported (novel) molecule HLA-C*03:02 potentially has a role to play in delaying the progression of among children in Africa. The findings can be placed in the middle of the existing controversial literature in this field; how? On the one hand, they found a substantial corroboration of the previous conclusions, especially among adults. Still, they also found evidence that the influence of these molecules in children may be different, especially given the genetic effect sizes of the novel molecules (from their research) compared to the canonical molecules. They are currently pursuing a more profound understanding of how HIV particles associate or interact with the novel HLA molecule to delay HIV progression to AIDS.

How has the work taking place changed or improved your understanding of your research?

“Quite substantially, I must say‼ Setting out to do this research more than four years ago, I was a novice in most of the subjects I have studied. Immunology is seen as a very complex subject for most medical students, and few ever understand the basic concepts of the immune system.” Samuel said. His attitude to this subject has seen a 180-degree change from a sceptic to a pessimist, and he believes he is more willing to write a research proposal in the area. His attitude to bioinformatics was that of fear and non-interest; in fact, he never wanted to look at the terminal on his laptop. Today, his terminal app is always open, and he uses it daily, which is a phenomenal transformation. He practically thinks about the various ways to improve his skills and application of the subject to solve problems in his community. These undertones run through his experiences with understanding of the utility and application of research.

Have you started to communicate and engage with communities, policymakers, or healthcare officials? If so, please discuss and share what actions you have taken and any impacts this has had. If not, please tell us how you hope this work can influence policy and/or healthcare initiatives.

None, to date, because he is still collecting more information that can coherently lead to a solid evidence-based community and policy engagement activity. Samuel is positively looking forward to this activity and responses from his engagements.