CCR2 is a minor coreceptor for human immune deficiency virus-1 (HIV-1) and its impact on HIV-1-related neuropsychological impairment (NPI) remains unknown. We studied the impact of CCR2-V64I polymorphisms on the development of NPI in 121 HIV-1 patients. The CCR2-64-I allele was associated with rate of progression to NPI when measured from the first study visit (Log Rank p=0.01) or from the estimated time of seroconversion (p=0.02). CCR2-V64I was not associated with plasma or CSF HIV-1 RNA load, suggesting that the impact of CCR2 on neuropathogenesis may involve alterations in inflammatory responses within the CNS rather than a direct impact on viral entry or replication.