Virological Efficacy in Cerebrospinal Fluid and Neurocognitive Status in Patients with Long-Term Monotherapy Based on Lopinavir/Ritonavir: An Exploratory Study

Abstract

BackgroundData on suppression of HIV replication in the CNS and on the subsequent risk of neurocognitive impairment using monotherapy with boosted protease inhibitors are limited.MethodsOurs was an exploratory cross-sectional study in patients on lopinavir/ritonavir-based monotherapy (LPV/r-MT) or standard triple therapy (LPV/r-ART) for at least 96 weeks who maintained a plasma viral load <50 copies/mL. HIV-1 RNA in CSF was determined by HIV-1 SuperLow assay (lower limit of detection, 1 copy/mL). Neurocognitive functioning was assessed using a recommended battery of neuropsychological tests covering 7 areas. Neurocognitive impairment (NCI) was determined and also a global deficit score (GDS) for study comparisons.ResultsSeventeen patients on LPV/r-MT and 17 on LPV/r-ART were included. Fourteen (82.4%) patients on LPV/r-MT and 16 (94.1%) on LPV/r-ART had HIV-1 RNA <1 copy/mL in CSF (p = 0.601). NCI was observed in 7 patients on LPV/r-MT and in 10 on LPV/r-ART (41% vs 59%; p = 0.494). Mean (SD) GDS was 0.22 (0.20) in patients on LPV/r-MT and 0.47 (0.34) in those on LPV/r-ART (p = 0.012).ConclusionsSuppression of HIV in CSF is similar in individuals with durable plasma HIV-1 RNA suppression who are receiving LPV/r-MT or LPV/r-ART for at least 96 weeks. Findings for HIV-1 replication in CSF and neurocognitive status indicate that this strategy seems to be safe for CNS functioning.

Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy

“…Using assays with a lower HIV RNA detection limit, estimated at 1 c/mL, the prevalence of asymptomatic CSF escape in the above study was 71 % (10/ 14) in monotherapy patients (compared to 50 %, 8/16 in patients on triple therapy [55]) and 11 % (2/17) in a crosssectional study of patients receiving long-term LPV/r monotherapy (compared to none of 17 patients on LPV/r-based cART) [54].…”

Short Communication: Focal Encephalitis Related to Viral Escape and Resistance Emergence in Cerebrospinal Fluid in a Patient on Lopinavir/Ritonavir Monotherapy with Plasma HIV-1 RNA Suppression

“…9,11 Recently, the prevalence of neurocognitive impairment in virologically suppressed patients on PI/r monotherapy was evaluated in two observational studies, and PI/r monotherapy was not associated with poorer neurocognitive performance compared to triple therapy. 24,25 In our case, the patient had a low nadir CD4 cell count and previous treatment failure with nucleoside reverse transcriptase inhibitors (NRTIs) and unboosted PIs; hence, although plasma viral load remained below the limit of detection and the patient was asymptomatic for a long time, we must emphasize that PI/r monotherapy was not a good simplification alternative according to current recommendations. 15,23 The presence of the M184V mutation suggests resistance selection while receiving lamivudine.…”

Prevalence and Correlates of Persistent HIV-1 RNA in Cerebrospinal Fluid During Antiretroviral Therapy

“…Our study is the largest to date, which may make our estimates more representative of clinical populations. While we used a different assay than prior studies, its accuracy has been previously validated in CSF [19]. CHARTER was designed to generalize to US clinical populations, but our study participants were a subgroup of the larger CHARTER cohort.…”

“…To measure HIV-1 RNA levels of <50 copies/mL, a validated single-copy assay procedure that has been used in other studies of HIV-1 RNA detection in CSF was used [19]. The HIV-1 SuperLow Assay (bioMONTR Labs) is a proprietary, modified version of the NucliSENS EasyQ assay (bioMèrieux) and is capable of quantifying HIV-1 levels as low as 1 copy/mL.…”