For patients, this has the major benefit that they can take less saquinavir, while maintaining sufficient saquinavir blood plasma levels to efficiently suppress the replication of HIV.The mechanism behind this welcome observation was not directly known, but later it was determined that ritonavir inhibits the cytochrome P450 3A4 isozyme. Normally, this enzyme metabolizes saquinavir to an inactive form, but with the ritonavir inhibiting this enzyme, the saquinavir blood plasma levels increased considerably. Additionally, ritonavir also inhibits multidrug transporters, although to a much lower extent.Unlike other protease inhibitors, the absorption of saquinavir seems to be improved by omeprazole. Mechanism of action
Saquinavir is a protease inhibitor. Proteases are enzymes that cleave protein molecules into smaller fragments. HIV protease is vital for both viral replication within the cell and release of mature viral particles from an infected cell. Saquinavir binds to the active site of the viral protease and prevents cleavage of viral polyproteins, preventing maturation of the virus. Saquinavir inhibits both HIV-1 and HIV-2 proteases. History
Saquinavir was developed by the pharmaceutical company Roche. Saquinavir was the sixth antiretroviral and the first protease inhibitor approved by the US Food and Drug Administration (FDA), leading ritonavir and indinavir by a few months.
1988: 10 families worldwide were identified as having CRV (now known as RVCL or RVCL-S)
1991: Related disease reported, HERNS (Hereditary Endiotheliopathy with Retinopathy, Nephropathy and Stroke – UCLA
1998: Related disease reported, HRV (Hereditary Retinal Vasculopathy) – Leiden University, Netherlands
2001: Localized to Chromosome 3. 2007: The specific genetic defect in all of these families was discovered in a single gene called TREX1 on chromosome 3. 2008: Name changed to AD-RVCL Autosomal Dominant-Retinal Vasculopathy with Cerebral Leukodystrophy
2009: Testing for the disease available to persons 21 and older
2011: 20 families worldwide were identified as having CRV
2012: Obtained mouse models for further research and to test therapeutic agents
2021: At least 42 families and 200 patients worldwide are known to have RVCL (or RVCL-S). [1]
2021: Dr. Jonathan Miner of the University of Pennsylvania (Penn) initiates the second clinical trial for RVCL, in collaboration with Dr. Andria Ford of WashU. Miner also establishes an International Registry in collaboration with colleagues. References


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