Platelet Microparticles, Platelet Activation and Platelet-Leukocyte Conjugates in HIV Infected Patients with Optimal Response to Highly Active Antiretroviral Therapy (HAART).

Background: HIV infection and its treatment have been associated with an increased risk of atherothrombotic cardiovascular disease. Little is known about the status of platelets in optimally controlled HIV infection. We aimed to assess the status of platelets using flow cytometry markers of platelet activation/apoptosis in HIV-infected patients who demonstrated an optimal response to highly active antiretroviral therapy (HAART).

Methods: In the current study we measured P-selectin expression in platelets, platelet microparticles (PMP) and platelet-leukocyte conjugates (PLC) by flow cytometry in 29 patients (mean age=42.1±7 years) with HIV infection on HAART who demonstrated an optimal viral and immunological response (CD4+ cell count > 200 /mm³ and undetectable viral load by ultrasensitive PCR analysis). Patients with a history of diabetes, smoking, illicit drug use, thrombotic, cardiovascular or malignant disease were excluded. We used age- and gender-matched healthy individuals as controls. PMP were measured by flow cytometry based in the co-expression of CD31 and CD42b. Platelet activation was also assessed by expression of activation marker P-selectin (expressed in fluorescence intensity units, FIU). PLC were measured based on the co-expression of CD45 and CD41 (expressed as percentage of leukocytes positive for CD41).

Results: Platelet expression of P-selectin was not significantly different between HIV infected patients (7.35 FIU; IQR=4.00–15.43) and controls (13.32 FIU; IQR=4.91–23.02; p=0.11). However, the levels of PMP were markedly elevated in HIV-infected patients (24,951 (counts/μl; IQR=17,887–36,175) compared to the control group (13,862 counts/μl; IQR=9,984–20,736; p=0.001). The levels of PLC were lower in HIV-infected patients (52.2%; IQR=42.65–65.75) compared to controls (63.8%; IQR=56.9–78.7; p=0.0007). There was a trend for a negative correlation between PMP levels and the CD4 count (Pearson R=−0.34; p=0.07).

Conclusions: HIV infected patients with optimal response to HAART demonstrate an increased number of circulating free PMP, normal levels of platelet expression of activation marker P-selectin and decreased levels of PLC. A decreased number of PLC indicates decreased binding of platelets and PMP to leukocytes in HIV-infected patients, which could be partially responsible for increased levels of free PMP. In addition, PMP (unlike P-selectin expression) may be a sensitive marker indicating low-grade platelet activation in HIV infection. Increased PMP levels are likely to contribute to the atherothrombotic risk HIV+ infected patients on HAART.