Long-term treated HIV infection is associated with platelet mitochondrial dysfunction

Area of Science:

• Mitochondrial biology
• Hematology
• Infectious diseases

Background:

• HIV infection and antiretroviral therapy are associated with mitochondrial dysfunction.
• Platelet mitochondrial dysfunction plays a role in thrombosis, immunoregulation, and age-related diseases.

Purpose of the Study:

• To investigate platelet mitochondrial DNA content (mtDNApl) and function in people living with HIV (PLHIV).
• To correlate these findings with platelet function and inflammatory markers.

Main Methods:

• Quantification of mtDNApl in 208 treated PLHIV and 56 controls.
• Assessment of platelet activation, reactivity, and inflammation using flow cytometry and circulating factors.
• Mitochondrial function tests and Seahorse Flux Analyzer in a subgroup.

Main Results:

• PLHIV had significantly lower mtDNApl compared to controls (p < 0.001).
• Prior zidovudine use showed a trend towards lower mtDNApl.
• PLHIV exhibited reduced ex vivo platelet reactivity and mean platelet volume.
• mtDNApl correlated positively with platelet parameters and negatively with sCD163.
• Platelet mitochondrial respiration defects were confirmed.

Conclusions:

• Platelet mitochondrial function is disturbed in people living with HIV.
• This dysfunction may contribute to platelet dysfunction and subsequent complications.
• Interventions to preserve platelet mitochondrial function could benefit PLHIV.