To confirm, among HIV1-infected patients, data from in vitro studies showing that antiretroviral therapies (ART) induce an accelerated aging through the same mechanism than genetic laminopathies (progeria) and « physiological » aging, i.e. through the synthesis and persistence of farnesylated prelamin A. The perspective is to minimize ART side effects using the same drug combination yet given to treat progeria children in Marseille.

A multicentric (Marseille, Nice and Montpellier Hospitals) 3 year-long study will analyse 50 HIV1-infected patients without any ART (A group), 100 infected patients receiving ART for at least 12 months (B group) and 50 age- and sex-matched seronegative control subjects. Infected patients will be submitted to 4 successive investigations (M0, M12, M24 and M36).

Biological tests are performed in Timone Hospital labs (Marseille): i/ viral load, PBMC isolation, DNA extraction, proviral DNA measurement [Virology]; ii/ CD4, CD8, glycemia, insulinemia, HOMA, total-, LDL- and HDL-cholesterol, triglycerides [Biochemistry labs from the 3 Hospitals]; iii/ ART assay [Pharmacokinetics Lab]; iv/ detection (western blot, immunocytochemistry) of PBMC nuclear, cytosolic and mitochondrial ART targets: A and B lamins, NF-kB and I-kB (proteasome activity), CD36 (glycosylation), mitochondrial Hsp70, ROS production, inner membrane potential, cytochrome C oxidase subunits 2 and 4 [Cell Biology]; v/ genotyping the ART targets: prelamin A and B processing proteases, Golgi SREBP-releasing proteases, mitochondrial deoxynucleoside transporters and proteases involved in nuclear-encoded protein import; telomere length [Molecular Genetics]. CIC-UPCET collaborated to the protocol design, recruits control subjects and is in charge of data statistical treatment.

The M0 collection just finished. Mitochondrial data will be presented.