Clinical trials

HIV/AIDS is a chronic disease that is difficult to eradicate because the virus persists as proviral DNA integrated into the host cells. Despite antiretroviral therapy, proviral DNA persists in lymphoid and myeloid reservoirs, whether circulating (memory CD4+ T cells) or tissue-based (macrophages). HIV reservoirs are highly heterogeneous, making it difficult to identify a specific biomarker or cell profile for a given reservoir. A distinctive feature of HIV reservoirs may be the selective interaction between reservoir cells and platelets. The presence of HIV in platelets could impact disease progression, particularly by triggering the reversal of HIV latency and leading to residual viral production. The frequency of platelets containing circulating virus in the blood is approximately 0.1% of the total platelet volume. Although seemingly negligible, this would represent a daily input of 10⁸ platelets harboring the virus. Furthermore, patients whose platelets contain HIV are primarily those with persistent immunological failure, known as "immunological non-responders" (InR). The regulation of the size (number and frequency) of the HIV reservoir by platelets is not known. However, HIV-containing platelets form more conjugates with CD4+ T cells than HIV-free platelets. While HIV-containing platelets do not productively infect cells, they induce metabolic dysfunction in CD4+ T cells (aerobic glycolysis). Increased aerobic glycolysis is a hallmark of T cell activation and senescence. This suggests an interconnection between the presence of the virus in platelets, the size of the reservoir, and immune dysfunction in HIV.

Rifampicin, is key in the treatment of staphylococcal PJIs. Rifabutin has a better profile of tolerance than rifampicin regarding the risk of interaction with concomitant medications and liver disorders. The hypothesis is that rifabutin may be an alternative antibiotic option as efficient as rifampicin for the treatment of staphylococcal PJIs, with a better safety profile. The investigator aim to demonstrate the non-inferiority of rifabutin as compared with rifampicin prescribed in combination treatment for PJIs.