Rapid Increase of Astrocytic and Inflammatory Markers in the Cerebrospinal Fluid of HIV+ Patients on LPV/r-Monotherapy (S57.006)

Objective: To determine biomarker(s) of early HIV escape in the cerebrospinal fluid (CSF). Background The MOST trial compared monotherapy with ritonavir-boosted lopinavir (MT) with continued therapy (CT). This trial had to be prematurely stopped due to blood viral failure in six patients on MT (Gutmann et al, AIDS 2010). It thus offers a unique opportunity to assess brain markers in the early stage of viral escape. Design/Methods: 61 CSF samples from 48 patients enrolled in MOST, including 34 CSF samples of CT and 27 of MT (mean duration on MT: 47+20 weeks) in patients who maintained full VL suppression in blood ( Results: In MT, concentrations of S100-beta (570±1132) and neopterin (2.5±2.9) were higher than in CT (0±532, p=0.002 and 1.2±2.5, p=0.058, respectively) and than in AD (173±214; p=0.0006 and 1.1±0.9; p=0.0014, respectively). In AD, concentration of Abeta (234+/-328) was lower than in CT (466±489, p=0.007) and MT (390±412, p=0.01) and concentrations of tTau (270±414) was higher than in CT (150±153, p=0.0078), but not than in MT (199±177, p=0.11). Conclusions: Despite full VL-suppression in blood, HIV monotherapy is sufficient to trigger inflammation and, especially, astrocytic damage. CSF markers of patients on CT have the same profile as reported for healthy subjects, suggesting that CT permits a good control of HIV in the brain. The levels of tTau, which are relatively similar between AD and MT patients, suggest that neurons are damaged during monotherapy. Supported by: Swiss HIV Cohort Study. Disclosure: Dr. Du Pasquier has received personal compensation for activities with Merck Serono, Biogen Idec, Abbott, and ViiV. Dr. Kalubi has nothing to disclose. Dr. Jilek has nothing to disclose. Dr. Yerly has received personal compensation for activities with Bristol-Myers Squibb Company, Gilead, ViiV, Merck Sharp & Dohme. Dr. Fux has nothing to disclose. Dr. Gutmann has nothing to disclose. Dr. Cusini has nothing to disclose. Dr. Cavassini has nothing to disclose. Dr. Opravil has nothing to disclose. Dr. Vernazza has received personal compensation for activities with Janssen, Gilead, and Bristol-Myers Squibb Company.