Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Dec 15;202(12):1819-25.
doi: 10.1086/657342. Epub 2010 Nov 4.

HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment

Arvid Edén  1 , Dietmar Fuchs, Lars Hagberg, Staffan Nilsson, Serena Spudich, Bo Svennerholm, Richard W Price, Magnus Gisslén
Affiliations

HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment

Arvid Edén et al. J Infect Dis. .

Abstract

Background: Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank.

Methods: Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay.

Results: Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54-213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels.

Conclusions: Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A, Cerebrospinal fluid (CSF) and plasma neopterin in relation to CSF human immunodeficiency virus type 1 (HIV-1) RNA. Neopterin values are log10 transformed. Dotted line represents normal reference value for neopterin. CSF neopterin was significantly higher in CSF viremic subjects (P=.03, t test). B, Total treatment time was significantly longer in CSF viremic subjects (P=.002 ; Mann-Whitney U test). C and D, the impact of central nervous system penetration effectiveness 2010 rank (CPE 2010-rank) on CSF viral load (C; P=.88) and CSF neopterin (D; r=0.009, P=.9).
Table 1
Table 1
Subject Characteristics
Table 2
Table 2
Distribution of Cerebrospinal Fluid (CSF) Viral Escape for Antiretroviral Drugs
See this image and copyright information in PMC

Comment in

References

    1. Gisslen M, Fuchs D, Svennerholm B, Hagberg L. Cerebrospinal fluid viral load, intrathecal immunoactivation, and cerebrospinal fluid monocytic cell count in HIV-1 infection. J Acquir Immune Defic Syndr. 1999;21:271–276. - PubMed
    1. Spudich SS, Nilsson AC, Lollo ND, et al. Cerebrospinal fluid HIV infection and pleocytosis: relation to systemic infection and antiretroviral treatment. BMC Infect Dis. 2005;5:98. - PMC - PubMed
    1. Ellis RJ, Hsia K, Spector SA, et al. Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome: HIV neurobehavioral research center group. Ann Neurol. 1997;42:679–688. - PubMed
    1. Antinori A, Arendt G, Becker JT, et al. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007;69:1789–1799. - PMC - PubMed
    1. Price RW, Brew BJ. The AIDS dementia complex. J Infect Dis. 1988;158:1079–1083. - PubMed

Publication types

MeSH terms