Delaying Megakaryocyte Apoptosis Normalizes Platelets in HIV Patients

ATLANTA—It appears that HIV-related thrombocytopenia can be corrected using a form of thrombopoietin to improve platelet production, Richard A. Carter, MD, of Emory University, said at the ASH meeting. He reported results of Amgen’s PEG-rHuMGDF (pegylated recombinant human megakaryocyte growth and development factor) in six HIV-infected thrombocytopenic patients.

He explained that thrombocytopenia in HIV patients is common, occurring in about one-third of individuals. It is due to a combination of shortened platelet lifespan, enhanced platelet splenic sequestration, and ineffective platelet production by megakaryocytes. A low platelet count generally leads to increased megakaryocyte production, but HIV can directly infect the megakaryocytes and induce apoptosis.

Dr. Carter noted that HIV also increases levels of endogenous thrombopoietin and increases the megakaryocyte mass, which increases platelet turnover but also results in defective delivery of platelets to the periphery.

The researchers hypothesized that thrombopoietic stimulation with PEG-rHuMGDF would normalize peripheral platelet counts in HIV-infected patients by improving the effectiveness of platelet production and stimulating megakaryocyte proliferation.

For the first month, patients were randomized to receive placebo or PEG-rHuMGDF, 5 µg/kg SC twice weekly. Placebo patients were given the growth factor after the first month, and all patients received it for 4 months.

“In all patients, platelet counts normalized in response to this dose, in most cases within 2 weeks,” Dr. Carter said. This occurred despite only a modest increase in platelet lifespan and reflected a “striking amplification in platelet turnover.”

The increase in peripheral platelet counts was 10-fold and was not associated with increased megakaryocyte mass, development of anti-PEG-rHu-MGDF antibodies, or increased HIV viral load.

Platelet counts were sustained throughout the 16 weeks of therapy but returned to thrombocytopenic baseline within 2 weeks after discontinuation. “This approach will require maintenance therapy,” he said.