Birgitta Anesten , Lars Hagberg , Henrik Zetterberg , Kaj Blennow , Magnus Gisslén , Aylin Yilmaz 
Affiliates:  Dpt of Infectious Diseases,  Dpt of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
In early phase of HIV infection, the virus invades the central nervous system and causes a chronic, progressive inflammation of the brain. Damage of the blood-brain barrier (BBB) is prevalent, mainly seen in patients with HIV associated dementia (HAD), but previous studies have confirmed BBB damage also in some untreated neuroasymptomatic HIV infected individuals. Since the introduction of modern antiretroviral therapy (ART) mortality and morbidity of HIV has remarkably reduced but the dynamics of BBB integrity prior and during treatment is not well studied. The aim of this study was to investigate the BBB integrity after initiation of modern antiretroviral therapy (ART).
Using a retrospective, longitudinal, observational study design and archived CSF samples from Department of Infectious Diseases, Sahlgrenska University Hospital, Göteborg, Sweden we studied BBB integrity as measured by CSF/plasma albumin ratio in 87 HIV-1 infected individuals. Neuroasymptomatic HIV infected antiretroviral treatment-naïve individuals and individuals off treatment for 6 months or more before initiation of ART, with >6 months of viral suppression to <50 copies/mL of HIV RNA in blood, were included. Albumin ratio was measured for each individual prior to and repeatedly during treatment for up to 12 years (in total 399 measurements).
Albumin ratios were age-adjusted to 43 years, the median age of subjects after all samples had been considered, this was based on 273 healthy HIV-negative controls. Normal age-adjusted reference value was < 9.9, based on the antilog of the log scale mean + 2 standard deviations (SD) in the 273 healthy controls.
In total, 13% of the individuals (11/87) had elevated age-adjusted albumin ratios. Seven percent (6/87) of the individuals had elevated age-adjusted albumin ratio at baseline. No significant change was found in albumin ratio after treatment initiation. Increased albumin ratio was found in 6% (5/87) after 1 year, 3% after 2 years, 2% (2/87) after 5 years and 2% (2/87) after 10 years ART.
A minority (7%) of neuroasymptomatic HIV-1 -infected individuals without treatment had signs of damaged BBB prior to treatment. Although ART did not significantly decrease age-adjusted albumin ratio in the full cohort, half (3/6) of those with increased levels normalised their levels within approximately 2 years and only 1 out of 6 had persistently increased albumin ratio after >10 years of treatment.