Streamlining the detection of latent HIV and investigating the causes of ineffective reactivation HIV incorporates its genetic material into that of an infected cell in a process called integration. Some of the integrated viruses can remain inactive, or become 'latent', but remain capable of reactivating later.  These viruses periodically reactivate meaning that, if treatment is stopped they can rekindle the infection, rendering HIV incurable.  One experimental approach to curing HIV is to reactivate these latent viruses whilst administering antiretroviral treatment at the same time, thereby flushing out the latent reservoir. Thus, it is crucial to be able to reactivate latent HIV effectively and measure the latent viral load efficiently.  The current gold standard measure of the latent HIV viral load is complex and labour intensive. It involves isolating the type of cells that harbour latent HIV, seeding them in defined small numbers in tissue culture wells, activating them, detecting proteins from reactivated viruses and working back to calculate the number of latently infected cells.  This process takes many days to yield a result. HIV is genetically diverse and my pilot data show that each latent virus is genetically distinct. Activating a sample will add reactivated viruses to the circulating population. Thus one expects an increase in the number of distinct viral sequences after latent viruses have been reactivated.  I will use modern sequencing methods and recently developed bioinformatics techniques to measure the number of viral sequences and correlate it with the latent viral load. This will reduce the amount of laboratory manipulation required for the assay.  Latent viruses are reactivated by activation of the cells containing them. However, even with the powerful stimuli currently available, only a minority can be reactivated.  I will generate cultures containing latent viruses. Some cultures will have only reactivatable viruses, some only non-reactivatable viruses. I will study why viral reactivation is ineffective, focusing on areas that have been overlooked in previous studies.  There is evidence that some cells can be induced to produce viral RNA, but not virus particles. It is possible that there are additional blocks in the way the cell processes viral RNA and produces viruses.  I will characterise these viral RNAs, sequence them and look for consistent mutations in apparently intact viral sequences that may account for their inability to produce virus.  We can potentially uncover novel viral encoded mechanisms through which RNA processing and production are controlled.  Most integrated viruses are defective or non-reactivatable. Reactivatable viruses constitute a small minority. It is possible that there are special features in the sites into which some viruses are integrated that make them susceptible to reactivation. Data from cell line models are inconsistent, and existing data from patient is derived from unselected cells and non-reactivable infected cells, both contain large proportions of defective viruses.  I will characterise the integration sites of reactivatable integrated viruses and identify features rendering the virus susceptible to reactivation. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.