Platelets Target the Circulating HIV Reservoir: Implications for Immunological Failure

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.

Inclusion Criteria: * Adult patients living with HIV with an undetectable viral load for more than 2 years * Beneficiary of a social security scheme or rightful claimant; * Patients able to read and understand the information sheet; * Having signed the consent form. Exclusion Criteria: * being unable to give free and informed consent; * pregnant or breastfeeding woman; * being under guardianship, curatorship, or a protection mandate;