The development of antiretroviral drugs over the past couple of decades has been commendable owing to the identification of several new targets within the overall HIV replication cycle. However, complete control over HIV/AIDS is yet to be achieved. This is because the current anti-HIV drugs, although effective in reducing plasma viral levels, cannot eradicate the virus completely from the body. This occurs because most anti-HIV drugs do not accumulate in certain cellular and anatomical reservoirs including the CNS. Insufficient delivery of anti-HIV drugs to the CNS is attributed to their low permeability across the BBB. Hence, low and sustained viral replication within the CNS continues even during prolonged antiretroviral drug therapy. Therefore, developing novel approaches that are targeted at enhancing the CNS delivery of anti-HIV drugs are required. In this review, we discuss the potential of nanocarriers and the role of cell-penetrating peptides in enhancing drug delivery to the CNS. Such drug delivery approaches could also lead to higher drug delivery to other cellular and anatomical reservoirs where the virus harbors than with conventional treatment, thus providing an effective therapy to eliminate the virus completely from the body.
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