Antiretroviral therapy regimens for neuro-AIDS

Abstract

In the era of highly active antiretroviral therapy (HAART) the central nervous system (CNS) becomes increasingly important as a sanctuary site for the human immunodeficiency virus (HIV-1). HIV-1-associated brain disease is subdivided into the minor cognitive/motor disorder, the minor cognitive/motor complex and the AIDS dementia complex, all of which are predictive for patients' deaths. CNS effective therapy therefore influences the prognosis of each individual patient. Thus, there is urgent need both for prophylactic and therapeutic strategies preventing or treating HIV-1-associated CNS disease. HAART consisting of two nucleoside analogues (NAs), one or two protease inhibitors (PIs) and/or one non-nucleoside inhibitor of the reverse transcriptase (NNRTI) has a neuroprophylactic value with regard to the manifestation of HIV-I associated CNS disease. With regard to therapeutic effects, the NAs zidovudine and stavudine penetrate into the cerebrospinal fluid and positively influence HIV-1-associated brain disease. Adding a second NA has no additional therapeutic effect. NNRTIs (nevirapine and efavirenz) are also CNS effective. However, there is a subgroup of non-responders, who obviously need other forms of therapeutic interventions. The very few existing studies point out that patients with high plasma viral loads and neurological abnormalities should be treated with a combination of two NAs and one NNRTI. The value of PIs for CNS protection remains to be evaluated.