MWESIGWA Savannah used Whole-exome sequencing (WES) to investigate two disease phenotypes; the first was pediatric HIV Long Term Non- Progression (LTNP) where 813 children from Uganda and Botswana were studied using WES in a non-traditional fashion by analyzing off-target reads from mitochondrial DNA and viral DNA. The second phenotype was hyper-hemolysis syndrome (HHS) in sickle cell disease (SCD) where 12 adults were studied using WES in the traditional approach by investigating the protein-coding variants. The study found that Anelloviridae co-infection was associated with an ex- tended AIDS-free period. Addition- ally, there was some evidence for reduced mitochondrial DNA copy numbers with increased highly active antiretroviral therapy (HAART) duration and participant age. For HHS in SCD, rare variants implicating dysfunction in the innate immune system were identified. These results demonstrate a broad application of WES to investigate the host and viral genetic factors influencing a spectrum of disease phenotypes. The study was funded by the Collaborative African Genomics Network (CAfGEN), H3Africa, and the National Institutes of Health and supervised by Prof. Moses Joloba, Dr. David Kateete, and Prof Graeme Mardon.