Platelet count kinetics following interruption of antiretroviral treatment

OBJECTIVES: To investigate the mechanisms of platelet kinetics in the SMART study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) (drug conservation [DC]) compared to continuous treatment (viral suppression [VS]). Follow up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. DESIGN: SMART patients from sites that determined platelets routinely. METHODS: Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. RESULTS:: Platelet levels decreased in the DC group following randomization, but remained stable in the VS group [median (IQR) decline from study entry to month 4: -24,000/μL(-54,000-4,000) vs. 3000 (-22,000-24,000), respectively, p < 0.0001)] and the rate of developing thrombocytopenia (<100,000/μL) was significantly higher in the DC versus the VS arm (unadjusted DC/VS HR (95%CI) = 1.8 (1.2-2.7)). The decline in platelet count among DC participants on fully suppressive ART correlated with the rise in D-dimer from baseline to either month 1 or 2 (r = -0.41; p = 0.02). Among DC participants who resumed ART 74% recovered to their study entry platelet levels. CONCLUSION: Interrupting ART increases the risk of thrombocytopenia, but re-initiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related pro-coagulant activity requires further study. (Less)