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

TitlePrevalence and Correlates of Persistent HIV-1 RNA in Cerebrospinal Fluid During Antiretroviral Therapy.
Publication TypeJournal Article
Year of Publication2017
AuthorsAnderson, AM, Muñoz-Moreno, JA, McClernon, DR, Ellis, RJ, Cookson, D, Clifford, DB, Collier, AC, Gelman, BB, Marra, CM, McArthur, JC, J McCutchan, A, Morgello, S, Sacktor, N, Simpson, DM, Franklin, DR, Heaton, RK, Grant, I, Letendre, SL
Corporate AuthorsCHARTER Group
JournalJ Infect Dis
Date Published2017 Jan 01
KeywordsAdult, Anti-HIV Agents, CD4 Lymphocyte Count, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, neurocognitive disorders, Prevalence, RNA, Viral, Viral Load

BACKGROUND:  Neurocognitive disorders remain common among human immunodeficiency virus (HIV)-positive adults, perhaps owing to persistent HIV-1 RNA in cerebrospinal fluid (CSF) during antiretroviral therapy (ART).METHODS:  Using a single-copy assay, we measured HIV-1 RNA levels in CSF and plasma specimens from 220 HIV-positive adults who were taking suppressive ART. Fifty-five participants were tested twice.RESULTS:  HIV-1 RNA was detected in 42.3% of CSF and 65.2% of plasma samples. Correlates of higher CSF HIV-1 RNA levels included higher nadir and current CD4 T-cell counts, a plasma HIV-1 RNA level of ≥ 1 copy/mL, and a lower central nervous system penetration-effectiveness score (model P < .001). Worse neurocognitive performance was associated with discordance in HIV-1 RNA detection between plasma and CSF, lower overall CSF HIV-1 RNA level, and longer ART duration, among others (model P < .001). In the longitudinal subgroup, CSF HIV-1 RNA persisted in most participants (69%) over 7 months.CONCLUSIONS:  Low-level HIV-1 RNA in CSF is common during suppressive ART and is associated with low-level HIV-1 RNA in blood, better immune status, and lower ART drug distribution into CSF. The association between HIV-1 RNA discordance and HIV-associated neurocognitive disorder (HAND) may reflect compartmentalization. The relationship between HAND, lower HIV-1 RNA levels in CSF, and lower CD4 T-cell counts may reflect disturbances in the immune response to HIV-1 in the CNS.

Alternate JournalJ Infect Dis
PubMed ID27789723
PubMed Central IDPMC5225254
Grant ListK24 MH097673 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
N01 MH022005 / MH / NIMH NIH HHS / United States
R01 MH107345 / MH / NIMH NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States
K23 MH095679 / MH / NIMH NIH HHS / United States