Antiretroviral treatment is generally highly effective in controlling HIV replication in the central nervous system (CNS), although resistance associated mutations may be locally selected 1. Drug ...passage into the CNS is known to be variable, being influenced by several parameters such as protein binding, molecular weight, lipophilicity, ionization, as well as by the presence of membrane transporters. According to a recently defined CNS drug penetration/effectiveness score, which was found to be associated to a significantly lower risk of viral replication in the cerebrospinal fluid (CSF), tenofovir and emtricitabine are classified as drugs with poor and good penetration, respectively 2. However, a high inter-individual variability of drug passage was recorded in pharmacokinetic studies. In this setting, the possible role of disrupted blood-brain barrier (BBB) deserves consideration, as altered BBB has been frequently reported in asymptomatic HIV-positive patients (2-22%) and in up to 100% of those with HIV-associated encephalitis 3,4. In other neurological diseases 5, drug penetration into CSF is known to be significantly affected by disruption of BBB, but only limited evidence of this is available in case of HIV-infected patients receiving antiretroviral treatment 6.