With the exception of hemolytic anemia, the potential hematological toxicity of antiretrovirals (ARV) and combination treatments in HIV treated individuals has not been well established. We report, for the first time, hematological toxicity defined as thrombocytosis in 9% of the HIV+ patients receiving highly active antiretroviral treatment (HAART) being followed in a nutritional clinical trial. Participants were evaluated every 6 months during a 2-year period (1998-2000) and blood drawn for biochemical, hematological and immunological parameters. NK cells were negatively correlated with platelet counts in the total cohort (P = 0.018) and persistently elevated with ARVT. Chronic thrombocytosis was associated with significantly lower NK percentages (P = 0.005). Twenty-five percent of the patients with thrombocytosis developed a cardiovascular disease. Together, these results support the proposal that HAART may increase the risk of hematological dysfunction and impact the risk of cardiovascular disease.