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

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 ac...

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Vydáno v:	The Journal of infectious diseases Ročník 202; číslo 12; s. 1819
Hlavní autoři:	Edén, Arvid, Fuchs, Dietmar, Hagberg, Lars, Nilsson, Staffan, Spudich, Serena, Svennerholm, Bo, Price, Richard W, Gisslén, Magnus
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 15.12.2010
Témata:	Adult Aged Anti-HIV Agents - pharmacokinetics Anti-HIV Agents - therapeutic use Blood-Brain Barrier Cerebrospinal Fluid - virology Cross-Sectional Studies Enzyme-Linked Immunosorbent Assay Female HIV Infections - drug therapy HIV Infections - virology HIV-1 - isolation & purification Humans Male Middle Aged Neopterin - analysis Plasma - virology Reverse Transcriptase Polymerase Chain Reaction RNA, Viral - isolation & purification Treatment Outcome Viral Load
ISSN:	1537-6613, 1537-6613
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Abstract	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. 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. 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. 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.
AbstractList	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.BACKGROUNDOccasional 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.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.METHODSSixty-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.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.RESULTSSeven (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.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.CONCLUSIONSViral 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. 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. 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. 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. 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.
Author	Nilsson, Staffan Svennerholm, Bo Gisslén, Magnus Fuchs, Dietmar Price, Richard W Spudich, Serena Edén, Arvid Hagberg, Lars
Author_xml	– sequence: 1 givenname: Arvid surname: Edén fullname: Edén, Arvid email: arvid.eden@vgregion.se organization: Department of Infectious Diseases, The Sahlgrenska Academy at University of Gothenburg, Sweden. arvid.eden@vgregion.se – sequence: 2 givenname: Dietmar surname: Fuchs fullname: Fuchs, Dietmar – sequence: 3 givenname: Lars surname: Hagberg fullname: Hagberg, Lars – sequence: 4 givenname: Staffan surname: Nilsson fullname: Nilsson, Staffan – sequence: 5 givenname: Serena surname: Spudich fullname: Spudich, Serena – sequence: 6 givenname: Bo surname: Svennerholm fullname: Svennerholm, Bo – sequence: 7 givenname: Richard W surname: Price fullname: Price, Richard W – sequence: 8 givenname: Magnus surname: Gisslén fullname: Gisslén, Magnus
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/21050119$$D View this record in MEDLINE/PubMed
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References	21628673 - J Infect Dis. 2011 Jul 1;204(1):174; author reply 174-5. doi: 10.1093/infdis/jir234. 21050117 - J Infect Dis. 2010 Dec 15;202(12):1768-9. doi: 10.1086/657343.
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SubjectTerms	Adult Aged Anti-HIV Agents - pharmacokinetics Anti-HIV Agents - therapeutic use Blood-Brain Barrier Cerebrospinal Fluid - virology Cross-Sectional Studies Enzyme-Linked Immunosorbent Assay Female HIV Infections - drug therapy HIV Infections - virology HIV-1 - isolation & purification Humans Male Middle Aged Neopterin - analysis Plasma - virology Reverse Transcriptase Polymerase Chain Reaction RNA, Viral - isolation & purification Treatment Outcome Viral Load
Title	HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment
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