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Erschienen in: Journal of NeuroVirology 1/2014

01.02.2014

Central nervous system antiretroviral penetration and cognitive functioning in largely pretreated HIV-infected patients

verfasst von: José L. Casado, Ana Marín, Ana Moreno, Verónica Iglesias, María J. Perez-Elías, Santiago Moreno, Iñigo Corral

Erschienen in: Journal of NeuroVirology | Ausgabe 1/2014

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Abstract

Prolonged time on effective antiretroviral therapy (ART) should be associated with a low incidence of neurocognitive impairment (NCI). We investigated the rate of NCI in 162 largely pretreated patients with HIV RNA suppression according to CNS antiretroviral drug penetration in comparison with 67 patients on their first ART line. Cognitive performance (Trailmaking A, B, Digit Symbol, Grooved Pegboard; demographically adjusted and converted to Z scores, NPZ4) was evaluated, and CNS penetration effectiveness (CPE) ranks of 1 to 4 were assigned and summed per regimen. After a median of 173.2 months on therapy (1,909.3 patients-year), the rate of NCI was similar in both groups (mean NPZ4, −0.24 vs −0.2). Pretreated patients received regimens with a CPE <7 in a large proportion (30 vs 9 %; p < 0.01). Patients in monotherapy had worse NPZ4 score than patients receiving triple therapy (−0.78 vs −0.18; p = 0.02; effect sizes 1.38), and a lower CPE score was observed in patients with a CD4+ count nadir <200 cells/ml with NCI (6.5 vs 7.3, p = 0.04). In the multivariate model, only the lowest CD4+ count and hepatitis C virus coinfection were associated with NPZ4, whereas CPE <7 showed a trend to association (p = 0.06) probably due to patients on monotherapy (estimate −0.33, p < 0.01). In conclusion, the rate of NCI in largely pretreated patients was similar to that observed in patients on their first regimen, and nadir CD4+ count continue to be critical. CNS drug penetration should be considered in cases of high risk for NCI.
Literatur
Zurück zum Zitat Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799PubMedCrossRef Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M et al (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799PubMedCrossRef
Zurück zum Zitat Antinori A, Giancola ML, Grisetti S, Soldani F, Alba L, Liuzzi G et al (2002) Factors influencing virological response to antiretroviral drugs in cerebrospinal fluid of advanced HIV-1-infected patients. AIDS 16:1867–1876PubMedCrossRef Antinori A, Giancola ML, Grisetti S, Soldani F, Alba L, Liuzzi G et al (2002) Factors influencing virological response to antiretroviral drugs in cerebrospinal fluid of advanced HIV-1-infected patients. AIDS 16:1867–1876PubMedCrossRef
Zurück zum Zitat Bhaskaran K, Mussini C, Antinori A, Walker AS, Dorrucci M, Sabin C et al (2008) Changes in the incidence and predictors of human immunodeficiency virus-associated dementia in the era of highly active antiretroviral therapy. Ann Neurol 63:213–221PubMedCrossRef Bhaskaran K, Mussini C, Antinori A, Walker AS, Dorrucci M, Sabin C et al (2008) Changes in the incidence and predictors of human immunodeficiency virus-associated dementia in the era of highly active antiretroviral therapy. Ann Neurol 63:213–221PubMedCrossRef
Zurück zum Zitat Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG et al (2010) Discordances between cerebrospinal fluid and plasma replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis 50:773–8. doi:10.1086/650538 PubMedCrossRef Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG et al (2010) Discordances between cerebrospinal fluid and plasma replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis 50:773–8. doi:10.​1086/​650538 PubMedCrossRef
Zurück zum Zitat Cysique L, Maruff P, Brew B (2004) Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J Neurovirol 10:350–357PubMedCrossRef Cysique L, Maruff P, Brew B (2004) Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: a combined study of two cohorts. J Neurovirol 10:350–357PubMedCrossRef
Zurück zum Zitat d’Arminio Monforte A, Cinque P, Mocroft A, Goebel FD, Antunes F, Katlama C et al (2004) Changing incidence of central nervous system diseases in the EuroSIDA cohort. Ann Neurol 55:320–328PubMedCrossRef d’Arminio Monforte A, Cinque P, Mocroft A, Goebel FD, Antunes F, Katlama C et al (2004) Changing incidence of central nervous system diseases in the EuroSIDA cohort. Ann Neurol 55:320–328PubMedCrossRef
Zurück zum Zitat Eggers C, Hertogs K, Sturenburg HJ, van Lunzen J, Stellbrink HJ (2003) Delayed central nervous system virus suppression during highly active antiretroviral therapy is associated with HIV encephalopathy, but not with viral drug resistance or poor central nervous system drug penetration. AIDS 17:1897–1906PubMedCrossRef Eggers C, Hertogs K, Sturenburg HJ, van Lunzen J, Stellbrink HJ (2003) Delayed central nervous system virus suppression during highly active antiretroviral therapy is associated with HIV encephalopathy, but not with viral drug resistance or poor central nervous system drug penetration. AIDS 17:1897–1906PubMedCrossRef
Zurück zum Zitat Ellis RJ, Evans SR, Clifford DB, Moo LR, McArthur JC, Collier AC et al (2005) Clinical validation of the NeuroScreen. J Neurovirol 11(6):503–511PubMedCrossRef Ellis RJ, Evans SR, Clifford DB, Moo LR, McArthur JC, Collier AC et al (2005) Clinical validation of the NeuroScreen. J Neurovirol 11(6):503–511PubMedCrossRef
Zurück zum Zitat Ellis RJ, Gamst AC, Capparelli E, Spector SA, Hsia K, Wolfson T et al (2000) Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology 54:927–936PubMedCrossRef Ellis RJ, Gamst AC, Capparelli E, Spector SA, Hsia K, Wolfson T et al (2000) Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology 54:927–936PubMedCrossRef
Zurück zum Zitat Ellis RJ, Moore DJ, Childers ME, Letendre S, McCutchan JA, Wolfson T et al (2002) Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA. Arch Neurol 59:923–928PubMedCrossRef Ellis RJ, Moore DJ, Childers ME, Letendre S, McCutchan JA, Wolfson T et al (2002) Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA. Arch Neurol 59:923–928PubMedCrossRef
Zurück zum Zitat Giancola ML, Lorenzini P, Balestra P, Larussa D, Baldini F, Corpolongo A et al (2006) Neuroactive antiretroviral drugs do not influence neurocognitive performance in less advanced HIV-infected patients responding to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 41:332–337PubMedCrossRef Giancola ML, Lorenzini P, Balestra P, Larussa D, Baldini F, Corpolongo A et al (2006) Neuroactive antiretroviral drugs do not influence neurocognitive performance in less advanced HIV-infected patients responding to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 41:332–337PubMedCrossRef
Zurück zum Zitat Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S et al (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17:3–16PubMedCentralPubMedCrossRef Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S et al (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17:3–16PubMedCentralPubMedCrossRef
Zurück zum Zitat Heaton RK, Marcotte TD, Mindt MR, Sadek J, Moore DJ, Bentley H et al (2004) The impact of HIV-associated neuropsychological impairment on everyday functioning. J Int Neuropsychol Soc 10:317–331PubMedCrossRef Heaton RK, Marcotte TD, Mindt MR, Sadek J, Moore DJ, Bentley H et al (2004) The impact of HIV-associated neuropsychological impairment on everyday functioning. J Int Neuropsychol Soc 10:317–331PubMedCrossRef
Zurück zum Zitat Letendre S (2011) Central nervous system complications in HIV disease: HIV-associated neurocognitive disorder. Top Antivir Med 19:137–42PubMed Letendre S (2011) Central nervous system complications in HIV disease: HIV-associated neurocognitive disorder. Top Antivir Med 19:137–42PubMed
Zurück zum Zitat Letendre S, McClernon D, Ellis R, et al. (2009). Persistent HIV in the central nervous system during treatment is associated with worse ART penetration and cognitive impairment. [Abstract 484b.] 16th Conference on Retroviruses and Opportunistic Infections (CROI). February 8-11; Montreal, Canada. Letendre S, McClernon D, Ellis R, et al. (2009). Persistent HIV in the central nervous system during treatment is associated with worse ART penetration and cognitive impairment. [Abstract 484b.] 16th Conference on Retroviruses and Opportunistic Infections (CROI). February 8-11; Montreal, Canada.
Zurück zum Zitat Price RW, Deeks SG (2004) Antiretroviral drug treatment interruption in human immunodeficiency virus infected adults: clinical and pathogenetic implications for the central nervous system. J Neurovirol 10(Suppl 1):44–51PubMed Price RW, Deeks SG (2004) Antiretroviral drug treatment interruption in human immunodeficiency virus infected adults: clinical and pathogenetic implications for the central nervous system. J Neurovirol 10(Suppl 1):44–51PubMed
Zurück zum Zitat Robertson KR, Smurzynski M, Parsons T, Wu K, Bosch R, Wu J et al (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 21:1915–1921PubMedCrossRef Robertson KR, Smurzynski M, Parsons T, Wu K, Bosch R, Wu J et al (2007) The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS 21:1915–1921PubMedCrossRef
Zurück zum Zitat Sacktor N, McDermott M, Marder K, Schifitto G, Selnes OA, McArthur JC et al (2002) HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol 8:136–142PubMedCrossRef Sacktor N, McDermott M, Marder K, Schifitto G, Selnes OA, McArthur JC et al (2002) HIV-associated cognitive impairment before and after the advent of combination therapy. J Neurovirol 8:136–142PubMedCrossRef
Zurück zum Zitat Simioni S, Cavassini M, Annoni JM, Rimbault Abraham A, Bourquin I, Schiffer V et al (2010) Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 24:1243–1250. doi:10.1097/QAD.0b013e3283354a7b PubMed Simioni S, Cavassini M, Annoni JM, Rimbault Abraham A, Bourquin I, Schiffer V et al (2010) Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 24:1243–1250. doi:10.​1097/​QAD.​0b013e3283354a7b​ PubMed
Zurück zum Zitat Tamarit MDP, Quereda C, Gonzalez-Rozas M, Corral I, Casado JL (2012) HIV-1 viral encephalitis after development of viral resistance to plasma suppressive antiretroviral therapy. AIDS Res Hum Retroviruses 28:83–86. doi:10.1089/AID.2011.0020 CrossRef Tamarit MDP, Quereda C, Gonzalez-Rozas M, Corral I, Casado JL (2012) HIV-1 viral encephalitis after development of viral resistance to plasma suppressive antiretroviral therapy. AIDS Res Hum Retroviruses 28:83–86. doi:10.​1089/​AID.​2011.​0020 CrossRef
Zurück zum Zitat Tozzi V, Balestra P, Bellagamba R, Corpolongo A, Salvatori MF, Visco-Comandini U et al (2007) Persistence of neuropsychological deficits despite long-term HAART in patients with HIV-related neurocognitive impairment. Prevalence and risk factors. J Acquir Immune Defic Syndr 45:174–182PubMedCrossRef Tozzi V, Balestra P, Bellagamba R, Corpolongo A, Salvatori MF, Visco-Comandini U et al (2007) Persistence of neuropsychological deficits despite long-term HAART in patients with HIV-related neurocognitive impairment. Prevalence and risk factors. J Acquir Immune Defic Syndr 45:174–182PubMedCrossRef
Zurück zum Zitat Tozzi V, Balestra P, Murri R, Galgani S, Bellagamba R, Narciso P et al (2004) Neurocognitive impairment influences quality of life in HIV-infected patients receiving HAART. Int J STD AIDS 15:254–259PubMedCrossRef Tozzi V, Balestra P, Murri R, Galgani S, Bellagamba R, Narciso P et al (2004) Neurocognitive impairment influences quality of life in HIV-infected patients receiving HAART. Int J STD AIDS 15:254–259PubMedCrossRef
Zurück zum Zitat Tozzi V, Balestra P, Salvatori MF, Vlassi C, Liuzzi G, Giancola ML et al (2009) Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. J Acquir Immune Defic Syndr 52:56–63PubMedCrossRef Tozzi V, Balestra P, Salvatori MF, Vlassi C, Liuzzi G, Giancola ML et al (2009) Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. J Acquir Immune Defic Syndr 52:56–63PubMedCrossRef
Zurück zum Zitat Yilmaz A, Svennerholm B, Hagberg L, Gisslen M (2006) Cerebrospinal fluid viral loads reach less than 2 copies/ml in HIV-1-infected patients with effective antiretroviral therapy. Antivir Ther 11:833–837PubMed Yilmaz A, Svennerholm B, Hagberg L, Gisslen M (2006) Cerebrospinal fluid viral loads reach less than 2 copies/ml in HIV-1-infected patients with effective antiretroviral therapy. Antivir Ther 11:833–837PubMed
Zurück zum Zitat Zigmond AS, Snaith RP (1984) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370CrossRef Zigmond AS, Snaith RP (1984) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370CrossRef
Metadaten
Titel
Central nervous system antiretroviral penetration and cognitive functioning in largely pretreated HIV-infected patients
verfasst von
José L. Casado
Ana Marín
Ana Moreno
Verónica Iglesias
María J. Perez-Elías
Santiago Moreno
Iñigo Corral
Publikationsdatum
01.02.2014
Verlag
Springer US
Erschienen in
Journal of NeuroVirology / Ausgabe 1/2014
Print ISSN: 1355-0284
Elektronische ISSN: 1538-2443
DOI
https://doi.org/10.1007/s13365-013-0228-0

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