SAPHIR addresses HIV latency in a focused and coherent manner profiting from an integrated approach by bringing highly complementary expertise of two Flemish universities, Ghent University and KU Leuven, together in one consortium. The project explored three missing gaps in our understanding of HIV latency such as:

i) the impact of the cellular HIV integration site on viral transcription using a new class of antiretroviral compounds (LEDGF/p75-IN inhibitors) as a tool to redirect HIV-1 integration;

ii) the importance of long noncoding RNA (lncRNA) in HIV latency; and

iii) the role of extracellular vesicles in latency and potential low level replication.  

SAPHIR addressed the unmet needs for efficient therapies and diagnostic assays for HIV-1: 

1. Define the impact of HIV-1 integration sites on the transcriptional status of the virus to better understand HIV persistence. 

2. Validate of a “block-and-lock” strategy by retargeting HIV-1 integration to non-functional integration sites in a pre-clinical model. 

3. Define the impact of HIV integration on clonal expansion in cells expressing immune-checkpoint markers. 

4. Validation of long non-coding RNAs that can be used as biomarker or define the reactivation potential of the reservoir.

5. Validation of at least one EV-based marker to measure the elimination of the HIV-1 reservoir in cell culture and relevant patient samples.