Background: The presence of active Human Immunodeficiency Virus (HIV) viral replication in the central nervous system (CNS) despite optimal plasma virological suppression is a largely unexplored issue, which is important for the understanding of HIV-associated neurocognitive diseases and development of drug resistance. We aimed to study the presence of detectable HIV RNA, as well as cerebrospinal fluid (CSF) drug levels, in a population of HIV-infected patients with HIV-associated dementia (HAD) and stable plasma virological suppression, in order to modify therapy and avoid further progression of the disease.

Patients and Methods: HIV-positive patients attending the University Department of Infectious Diseases in Brescia (Northern Italy), with a previous diagnosis of HAD, on both stable Highly Active Antiretroviral Therapy (HAART) and plasma HIV RNA <37 copies/mL for at least 6 months underwent lumbar puncture (LP) in order to study HIV RNA and antiretroviral concentrations in the CSF.

Results: Fifteen subjects were included in the analysis. Mean age was 51 years, 13 patients were males. Eight patients were injection drug users. Mean nadir CD4+ T-cell count was 99cells/µL. Mean time from HAD diagnosis was 9 years. Eight patients experienced more than 5 lines of HAART and 13 patients were on PI-boosted regimens. Only one patient had detectable HIV RNA in CSF (130 copies/mL) with a pattern of widespread drug resistance. As for CSF antiretroviral drug concentrations, allsamples showed detectable levels, but atazanavir concentrations were significantly lowerin the patient with CSF viral escape (1.1 ng/mL) compared to the other patients on the same PI (range: 3.5-40.3 ng/mL).

Conclusions: In our study, only one out of fifteen patients had CSF viral escape. However, a cautious approach would suggest to perform screening LP in patients with previous HAD who could experience severe clinical deterioration. Indeed HIV may replicate in CSF despite low viral levels or viral suppression in the blood compartment, resulting in acute or subacute neurocognitive impairment.