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Treatment intensification has no effect on the HIV-1 central nervous system infection in patients on suppressive antiretroviral therapy

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Abstract
Background: Antiretroviral treatment (ART) significantly reduces cerebrospinal fluid (CSF) HIV-1 RNA levels and residual viremia is less frequently found in CSF than in blood. However, persistent intrathecal immunoactivation is common, even after several years of ART. To investigate whether low-level CSF viremia and residual immunoactivation within the central nervous system (CNS) derive from ongoing local viral replication, we conducted a study of treatment intensification in patients on effective ART. Methods: Ten patients on ART with plasma HIV RNA,50 copies per milliliter for. 18 months were included. Intensification was given for in total 8 weeks: 4 weeks with maraviroc or lopinavir/ritonavir (good CNS penetration), and 4 weeks with enfuvirtide (poor CNS penetration). Lumbar punctures were performed 4 weeks before, at intensification commencement, at switchover after 4 weeks, at the conclusion of, and 4 weeks after the intensification period. Results: No significant changes in HIV RNA, neopterin, beta 2-microglobulin, immunoglobulin G index, albumin ratio, and CD4(+) T-cell count were observed, either in CSF or blood, neither before, during, nor after the intensification periods. Conclusions: ART intensification did not reduce residual CSF HIV RNA levels or intrathecal immunoactivation in patients on ART. These findings do not support an ongoing viral replication in CNS.
Keywords
VIRAL LOAD, antiretroviral drug intensification, COMBINATION THERAPY, cerebrospinal fluid, viral reservoir, NEUROLOGICAL DISORDERS, HIV RNA, REFERENCE VALUES, LOPINAVIR CONCENTRATIONS, HIV-1-INFECTED PATIENTS, CEREBROSPINAL-FLUID, CD4(+) T-CELLS, NEOPTERIN CONCENTRATIONS, INTRATHECAL IMMUNOACTIVATION

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Citation

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Chicago
Yilmaz, Aylin, Chris Verhofstede, Antonio D’Avolio, Victoria Watson, Lars Hagberg, Dietmar Fuchs, Bo Svennerholm, and Magnus Gisslen. 2010. “Treatment Intensification Has No Effect on the HIV-1 Central Nervous System Infection in Patients on Suppressive Antiretroviral Therapy.” Jaids-journal of Acquired Immune Deficiency Syndromes 55 (5): 590–596.
APA
Yilmaz, Aylin, Verhofstede, C., D’Avolio, A., Watson, V., Hagberg, L., Fuchs, D., Svennerholm, B., et al. (2010). Treatment intensification has no effect on the HIV-1 central nervous system infection in patients on suppressive antiretroviral therapy. JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 55(5), 590–596.
Vancouver
1.
Yilmaz A, Verhofstede C, D’Avolio A, Watson V, Hagberg L, Fuchs D, et al. Treatment intensification has no effect on the HIV-1 central nervous system infection in patients on suppressive antiretroviral therapy. JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES. 2010;55(5):590–6.
MLA
Yilmaz, Aylin, Chris Verhofstede, Antonio D’Avolio, et al. “Treatment Intensification Has No Effect on the HIV-1 Central Nervous System Infection in Patients on Suppressive Antiretroviral Therapy.” JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES 55.5 (2010): 590–596. Print.
@article{1233558,
  abstract     = {Background: Antiretroviral treatment (ART) significantly reduces cerebrospinal fluid (CSF) HIV-1 RNA levels and residual viremia is less frequently found in CSF than in blood. However, persistent intrathecal immunoactivation is common, even after several years of ART. To investigate whether low-level CSF viremia and residual immunoactivation within the central nervous system (CNS) derive from ongoing local viral replication, we conducted a study of treatment intensification in patients on effective ART. Methods: Ten patients on ART with plasma HIV RNA,50 copies per milliliter for. 18 months were included. Intensification was given for in total 8 weeks: 4 weeks with maraviroc or lopinavir/ritonavir (good CNS penetration), and 4 weeks with enfuvirtide (poor CNS penetration). Lumbar punctures were performed 4 weeks before, at intensification commencement, at switchover after 4 weeks, at the conclusion of, and 4 weeks after the intensification period. Results: No significant changes in HIV RNA, neopterin, beta 2-microglobulin, immunoglobulin G index, albumin ratio, and CD4(+) T-cell count were observed, either in CSF or blood, neither before, during, nor after the intensification periods. Conclusions: ART intensification did not reduce residual CSF HIV RNA levels or intrathecal immunoactivation in patients on ART. These findings do not support an ongoing viral replication in CNS.},
  author       = {Yilmaz, Aylin and Verhofstede, Chris and D'Avolio, Antonio and Watson, Victoria and Hagberg, Lars and Fuchs, Dietmar and Svennerholm, Bo and Gisslen, Magnus},
  issn         = {1525-4135},
  journal      = {JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES},
  keyword      = {VIRAL LOAD,antiretroviral drug intensification,COMBINATION THERAPY,cerebrospinal fluid,viral reservoir,NEUROLOGICAL DISORDERS,HIV RNA,REFERENCE VALUES,LOPINAVIR CONCENTRATIONS,HIV-1-INFECTED PATIENTS,CEREBROSPINAL-FLUID,CD4(+) T-CELLS,NEOPTERIN CONCENTRATIONS,INTRATHECAL IMMUNOACTIVATION},
  language     = {eng},
  number       = {5},
  pages        = {590--596},
  title        = {Treatment intensification has no effect on the HIV-1 central nervous system infection in patients on suppressive antiretroviral therapy},
  url          = {http://dx.doi.org/10.1097/QAI.0b013e3181f5b3d1},
  volume       = {55},
  year         = {2010},
}

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