Neurological outcomes in late HIV infection: Adverse impact of neurological impairment on survival and protective effect of antiviral therapy

Richard W. Price, Constantin Yiannoutsos, David B. Clifford, Lawrence Zaborski, Alex Tselis, John J. Sidtis, Bruce Cohen, Colin D. Hall, Alejo Erice, Keith Henry, M. Glicksman, W. G. Powderly, S. Swindells, G. Rudberg, C. Cooper, H. Kessler, M. Borucki, P. Galatas, C. Van der Horst, C. KapoorK. Robertson, W. Robertson, D. Simpson, D. Dorfman, B. Sinclair, C. Olson, K. Marder, M. Crawford, T. Flynn, C. Wanke, D. Craven, J. Reid, R. Holloway, Kenneth Fife, K. Todd, C. M. Marra, A. C. Collier, D. Cummings, K. L. Tyler, B. A. Putnam, H. Hollander, J. Walker, I. Matozzo, I. Frank, P. Kumar, M. Guerrero, S. Kruger, M. Fischl, E. Scerpella, A. Rodriguez, P. T. Frame, S. Kohrs, M. Lederman, G. Vazquez, I. Lopez, R. Delapenha, Y. Butler, M. Saag, K. E. Squires, S. Deloach, B. McCulloch, E. Cooney, C. Frank, M. J. Nealon, L. Ponticello, R. Sociro, F. Valentine, M. Vogler, K. Chirgwin, S. Szebenyi, M. Rinki, D. Slamowitz, D. Ogata-Arakaki, M. Millard, R. Ellis, R. Snyder, M. E. Eyster, C. Ehmann, C. Kessler, C. Quinlan, D. B. Brettler, P. Forand, S. Seremetis, M. Brady, J. Hunkler, H. Saba, B. Tannenbaum, K. Hoots, T. D. Coates, A. Sosa, M. A. South, A. Rubinstein, J. Weiler-Einstein, J. Gill, P. Timmons, S. Stabler, S. Giambartolomei, P. Clax, A. Kenton

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Objective: In a large multi-center clinical trial of combination reverse transcriptase inhibitors (RTIs), we assessed the impact of antiretroviral therapy on neurological function, the relationship between neurological and systemic benefit, and the prognostic value of neurological performance in late HIV-1 infection. Design: Neurological evaluations incorporated in a randomized, multi-center trial of combination antiretroviral therapy. Setting: Forty-two AIDS Clinical Trials Group sites and seven National Hemophilia Foundation sites Patients: Adult HIV-infected patients (n = 1313) with CD4 counts <50 x 106 cells/l. Interventions: Four combinations of reverse transcriptase inhibitors consisting of zidovudine (ZDV), alternating monthly with didanosine (ddl), or in combination with zalcitabine (ddC), ddl or ddl and nevirapine. Main outcome measures: Mean change from baseline of a four-item quantitative neurological performance battery score, the QNPZ-4, administered to 1031 subjects. Results: Triple therapy and ZDV/ddl combination preserved or improved neurological performance over time compared with the alternating ZDV/ddl and ZDV/ddC regimens (P <0.001), paralleling their impact on survival in the same trial as previously reported. QNPZ-4 scores were predictive of survival (P <0.001), after adjusting for CD4 counts and HIV-1 plasma RNA concentrations. Conclusions: Combination antiretroviral therapy can have a salutary effect on preserving or improving neurological function. Superior systemic treatments may likewise better preserve neurological function. The significant association of poor neurological performance with mortality, independent of CD4 counts and HIV-1 RNA levels indicates that neurological dysfunction is an important cause or a strong marker of poor prognosis in late HIV-1 infection. This study demonstrates the value of adjunctive neurological measures in large therapeutic trials of late HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)1677-1685
Number of pages9
JournalAIDS
Volume13
Issue number13
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

HIV Infections
Antiviral Agents
Zidovudine
HIV-1
Survival
CD4 Lymphocyte Count
Reverse Transcriptase Inhibitors
Therapeutics
Zalcitabine
Clinical Trials
RNA
Didanosine
Nevirapine
Hemophilia A
Acquired Immunodeficiency Syndrome
Outcome Assessment (Health Care)
HIV
Mortality

Keywords

  • AIDS dementia complex
  • Antiretroviral therapy
  • CD4 T lymphocytes
  • Central nervous system
  • Didanosine
  • Neuropsychological test
  • Nevirapine
  • Reverse transcriptase inhibitors
  • Viral load
  • Zalcitabine
  • Zidovudine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Neurological outcomes in late HIV infection : Adverse impact of neurological impairment on survival and protective effect of antiviral therapy. / Price, Richard W.; Yiannoutsos, Constantin; Clifford, David B.; Zaborski, Lawrence; Tselis, Alex; Sidtis, John J.; Cohen, Bruce; Hall, Colin D.; Erice, Alejo; Henry, Keith; Glicksman, M.; Powderly, W. G.; Swindells, S.; Rudberg, G.; Cooper, C.; Kessler, H.; Borucki, M.; Galatas, P.; Van der Horst, C.; Kapoor, C.; Robertson, K.; Robertson, W.; Simpson, D.; Dorfman, D.; Sinclair, B.; Olson, C.; Marder, K.; Crawford, M.; Flynn, T.; Wanke, C.; Craven, D.; Reid, J.; Holloway, R.; Fife, Kenneth; Todd, K.; Marra, C. M.; Collier, A. C.; Cummings, D.; Tyler, K. L.; Putnam, B. A.; Hollander, H.; Walker, J.; Matozzo, I.; Frank, I.; Kumar, P.; Guerrero, M.; Kruger, S.; Fischl, M.; Scerpella, E.; Rodriguez, A.; Frame, P. T.; Kohrs, S.; Lederman, M.; Vazquez, G.; Lopez, I.; Delapenha, R.; Butler, Y.; Saag, M.; Squires, K. E.; Deloach, S.; McCulloch, B.; Cooney, E.; Frank, C.; Nealon, M. J.; Ponticello, L.; Sociro, R.; Valentine, F.; Vogler, M.; Chirgwin, K.; Szebenyi, S.; Rinki, M.; Slamowitz, D.; Ogata-Arakaki, D.; Millard, M.; Ellis, R.; Snyder, R.; Eyster, M. E.; Ehmann, C.; Kessler, C.; Quinlan, C.; Brettler, D. B.; Forand, P.; Seremetis, S.; Brady, M.; Hunkler, J.; Saba, H.; Tannenbaum, B.; Hoots, K.; Coates, T. D.; Sosa, A.; South, M. A.; Rubinstein, A.; Weiler-Einstein, J.; Gill, J.; Timmons, P.; Stabler, S.; Giambartolomei, S.; Clax, P.; Kenton, A.

In: AIDS, Vol. 13, No. 13, 1999, p. 1677-1685.

Research output: Contribution to journalArticle

Price, RW, Yiannoutsos, C, Clifford, DB, Zaborski, L, Tselis, A, Sidtis, JJ, Cohen, B, Hall, CD, Erice, A, Henry, K, Glicksman, M, Powderly, WG, Swindells, S, Rudberg, G, Cooper, C, Kessler, H, Borucki, M, Galatas, P, Van der Horst, C, Kapoor, C, Robertson, K, Robertson, W, Simpson, D, Dorfman, D, Sinclair, B, Olson, C, Marder, K, Crawford, M, Flynn, T, Wanke, C, Craven, D, Reid, J, Holloway, R, Fife, K, Todd, K, Marra, CM, Collier, AC, Cummings, D, Tyler, KL, Putnam, BA, Hollander, H, Walker, J, Matozzo, I, Frank, I, Kumar, P, Guerrero, M, Kruger, S, Fischl, M, Scerpella, E, Rodriguez, A, Frame, PT, Kohrs, S, Lederman, M, Vazquez, G, Lopez, I, Delapenha, R, Butler, Y, Saag, M, Squires, KE, Deloach, S, McCulloch, B, Cooney, E, Frank, C, Nealon, MJ, Ponticello, L, Sociro, R, Valentine, F, Vogler, M, Chirgwin, K, Szebenyi, S, Rinki, M, Slamowitz, D, Ogata-Arakaki, D, Millard, M, Ellis, R, Snyder, R, Eyster, ME, Ehmann, C, Kessler, C, Quinlan, C, Brettler, DB, Forand, P, Seremetis, S, Brady, M, Hunkler, J, Saba, H, Tannenbaum, B, Hoots, K, Coates, TD, Sosa, A, South, MA, Rubinstein, A, Weiler-Einstein, J, Gill, J, Timmons, P, Stabler, S, Giambartolomei, S, Clax, P & Kenton, A 1999, 'Neurological outcomes in late HIV infection: Adverse impact of neurological impairment on survival and protective effect of antiviral therapy', AIDS, vol. 13, no. 13, pp. 1677-1685. https://doi.org/10.1097/00002030-199909100-00011
Price, Richard W. ; Yiannoutsos, Constantin ; Clifford, David B. ; Zaborski, Lawrence ; Tselis, Alex ; Sidtis, John J. ; Cohen, Bruce ; Hall, Colin D. ; Erice, Alejo ; Henry, Keith ; Glicksman, M. ; Powderly, W. G. ; Swindells, S. ; Rudberg, G. ; Cooper, C. ; Kessler, H. ; Borucki, M. ; Galatas, P. ; Van der Horst, C. ; Kapoor, C. ; Robertson, K. ; Robertson, W. ; Simpson, D. ; Dorfman, D. ; Sinclair, B. ; Olson, C. ; Marder, K. ; Crawford, M. ; Flynn, T. ; Wanke, C. ; Craven, D. ; Reid, J. ; Holloway, R. ; Fife, Kenneth ; Todd, K. ; Marra, C. M. ; Collier, A. C. ; Cummings, D. ; Tyler, K. L. ; Putnam, B. A. ; Hollander, H. ; Walker, J. ; Matozzo, I. ; Frank, I. ; Kumar, P. ; Guerrero, M. ; Kruger, S. ; Fischl, M. ; Scerpella, E. ; Rodriguez, A. ; Frame, P. T. ; Kohrs, S. ; Lederman, M. ; Vazquez, G. ; Lopez, I. ; Delapenha, R. ; Butler, Y. ; Saag, M. ; Squires, K. E. ; Deloach, S. ; McCulloch, B. ; Cooney, E. ; Frank, C. ; Nealon, M. J. ; Ponticello, L. ; Sociro, R. ; Valentine, F. ; Vogler, M. ; Chirgwin, K. ; Szebenyi, S. ; Rinki, M. ; Slamowitz, D. ; Ogata-Arakaki, D. ; Millard, M. ; Ellis, R. ; Snyder, R. ; Eyster, M. E. ; Ehmann, C. ; Kessler, C. ; Quinlan, C. ; Brettler, D. B. ; Forand, P. ; Seremetis, S. ; Brady, M. ; Hunkler, J. ; Saba, H. ; Tannenbaum, B. ; Hoots, K. ; Coates, T. D. ; Sosa, A. ; South, M. A. ; Rubinstein, A. ; Weiler-Einstein, J. ; Gill, J. ; Timmons, P. ; Stabler, S. ; Giambartolomei, S. ; Clax, P. ; Kenton, A. / Neurological outcomes in late HIV infection : Adverse impact of neurological impairment on survival and protective effect of antiviral therapy. In: AIDS. 1999 ; Vol. 13, No. 13. pp. 1677-1685.
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title = "Neurological outcomes in late HIV infection: Adverse impact of neurological impairment on survival and protective effect of antiviral therapy",
abstract = "Objective: In a large multi-center clinical trial of combination reverse transcriptase inhibitors (RTIs), we assessed the impact of antiretroviral therapy on neurological function, the relationship between neurological and systemic benefit, and the prognostic value of neurological performance in late HIV-1 infection. Design: Neurological evaluations incorporated in a randomized, multi-center trial of combination antiretroviral therapy. Setting: Forty-two AIDS Clinical Trials Group sites and seven National Hemophilia Foundation sites Patients: Adult HIV-infected patients (n = 1313) with CD4 counts <50 x 106 cells/l. Interventions: Four combinations of reverse transcriptase inhibitors consisting of zidovudine (ZDV), alternating monthly with didanosine (ddl), or in combination with zalcitabine (ddC), ddl or ddl and nevirapine. Main outcome measures: Mean change from baseline of a four-item quantitative neurological performance battery score, the QNPZ-4, administered to 1031 subjects. Results: Triple therapy and ZDV/ddl combination preserved or improved neurological performance over time compared with the alternating ZDV/ddl and ZDV/ddC regimens (P <0.001), paralleling their impact on survival in the same trial as previously reported. QNPZ-4 scores were predictive of survival (P <0.001), after adjusting for CD4 counts and HIV-1 plasma RNA concentrations. Conclusions: Combination antiretroviral therapy can have a salutary effect on preserving or improving neurological function. Superior systemic treatments may likewise better preserve neurological function. The significant association of poor neurological performance with mortality, independent of CD4 counts and HIV-1 RNA levels indicates that neurological dysfunction is an important cause or a strong marker of poor prognosis in late HIV-1 infection. This study demonstrates the value of adjunctive neurological measures in large therapeutic trials of late HIV-1 infection.",
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doi = "10.1097/00002030-199909100-00011",
language = "English (US)",
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pages = "1677--1685",
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TY - JOUR

T1 - Neurological outcomes in late HIV infection

T2 - Adverse impact of neurological impairment on survival and protective effect of antiviral therapy

AU - Price, Richard W.

AU - Yiannoutsos, Constantin

AU - Clifford, David B.

AU - Zaborski, Lawrence

AU - Tselis, Alex

AU - Sidtis, John J.

AU - Cohen, Bruce

AU - Hall, Colin D.

AU - Erice, Alejo

AU - Henry, Keith

AU - Glicksman, M.

AU - Powderly, W. G.

AU - Swindells, S.

AU - Rudberg, G.

AU - Cooper, C.

AU - Kessler, H.

AU - Borucki, M.

AU - Galatas, P.

AU - Van der Horst, C.

AU - Kapoor, C.

AU - Robertson, K.

AU - Robertson, W.

AU - Simpson, D.

AU - Dorfman, D.

AU - Sinclair, B.

AU - Olson, C.

AU - Marder, K.

AU - Crawford, M.

AU - Flynn, T.

AU - Wanke, C.

AU - Craven, D.

AU - Reid, J.

AU - Holloway, R.

AU - Fife, Kenneth

AU - Todd, K.

AU - Marra, C. M.

AU - Collier, A. C.

AU - Cummings, D.

AU - Tyler, K. L.

AU - Putnam, B. A.

AU - Hollander, H.

AU - Walker, J.

AU - Matozzo, I.

AU - Frank, I.

AU - Kumar, P.

AU - Guerrero, M.

AU - Kruger, S.

AU - Fischl, M.

AU - Scerpella, E.

AU - Rodriguez, A.

AU - Frame, P. T.

AU - Kohrs, S.

AU - Lederman, M.

AU - Vazquez, G.

AU - Lopez, I.

AU - Delapenha, R.

AU - Butler, Y.

AU - Saag, M.

AU - Squires, K. E.

AU - Deloach, S.

AU - McCulloch, B.

AU - Cooney, E.

AU - Frank, C.

AU - Nealon, M. J.

AU - Ponticello, L.

AU - Sociro, R.

AU - Valentine, F.

AU - Vogler, M.

AU - Chirgwin, K.

AU - Szebenyi, S.

AU - Rinki, M.

AU - Slamowitz, D.

AU - Ogata-Arakaki, D.

AU - Millard, M.

AU - Ellis, R.

AU - Snyder, R.

AU - Eyster, M. E.

AU - Ehmann, C.

AU - Kessler, C.

AU - Quinlan, C.

AU - Brettler, D. B.

AU - Forand, P.

AU - Seremetis, S.

AU - Brady, M.

AU - Hunkler, J.

AU - Saba, H.

AU - Tannenbaum, B.

AU - Hoots, K.

AU - Coates, T. D.

AU - Sosa, A.

AU - South, M. A.

AU - Rubinstein, A.

AU - Weiler-Einstein, J.

AU - Gill, J.

AU - Timmons, P.

AU - Stabler, S.

AU - Giambartolomei, S.

AU - Clax, P.

AU - Kenton, A.

PY - 1999

Y1 - 1999

N2 - Objective: In a large multi-center clinical trial of combination reverse transcriptase inhibitors (RTIs), we assessed the impact of antiretroviral therapy on neurological function, the relationship between neurological and systemic benefit, and the prognostic value of neurological performance in late HIV-1 infection. Design: Neurological evaluations incorporated in a randomized, multi-center trial of combination antiretroviral therapy. Setting: Forty-two AIDS Clinical Trials Group sites and seven National Hemophilia Foundation sites Patients: Adult HIV-infected patients (n = 1313) with CD4 counts <50 x 106 cells/l. Interventions: Four combinations of reverse transcriptase inhibitors consisting of zidovudine (ZDV), alternating monthly with didanosine (ddl), or in combination with zalcitabine (ddC), ddl or ddl and nevirapine. Main outcome measures: Mean change from baseline of a four-item quantitative neurological performance battery score, the QNPZ-4, administered to 1031 subjects. Results: Triple therapy and ZDV/ddl combination preserved or improved neurological performance over time compared with the alternating ZDV/ddl and ZDV/ddC regimens (P <0.001), paralleling their impact on survival in the same trial as previously reported. QNPZ-4 scores were predictive of survival (P <0.001), after adjusting for CD4 counts and HIV-1 plasma RNA concentrations. Conclusions: Combination antiretroviral therapy can have a salutary effect on preserving or improving neurological function. Superior systemic treatments may likewise better preserve neurological function. The significant association of poor neurological performance with mortality, independent of CD4 counts and HIV-1 RNA levels indicates that neurological dysfunction is an important cause or a strong marker of poor prognosis in late HIV-1 infection. This study demonstrates the value of adjunctive neurological measures in large therapeutic trials of late HIV-1 infection.

AB - Objective: In a large multi-center clinical trial of combination reverse transcriptase inhibitors (RTIs), we assessed the impact of antiretroviral therapy on neurological function, the relationship between neurological and systemic benefit, and the prognostic value of neurological performance in late HIV-1 infection. Design: Neurological evaluations incorporated in a randomized, multi-center trial of combination antiretroviral therapy. Setting: Forty-two AIDS Clinical Trials Group sites and seven National Hemophilia Foundation sites Patients: Adult HIV-infected patients (n = 1313) with CD4 counts <50 x 106 cells/l. Interventions: Four combinations of reverse transcriptase inhibitors consisting of zidovudine (ZDV), alternating monthly with didanosine (ddl), or in combination with zalcitabine (ddC), ddl or ddl and nevirapine. Main outcome measures: Mean change from baseline of a four-item quantitative neurological performance battery score, the QNPZ-4, administered to 1031 subjects. Results: Triple therapy and ZDV/ddl combination preserved or improved neurological performance over time compared with the alternating ZDV/ddl and ZDV/ddC regimens (P <0.001), paralleling their impact on survival in the same trial as previously reported. QNPZ-4 scores were predictive of survival (P <0.001), after adjusting for CD4 counts and HIV-1 plasma RNA concentrations. Conclusions: Combination antiretroviral therapy can have a salutary effect on preserving or improving neurological function. Superior systemic treatments may likewise better preserve neurological function. The significant association of poor neurological performance with mortality, independent of CD4 counts and HIV-1 RNA levels indicates that neurological dysfunction is an important cause or a strong marker of poor prognosis in late HIV-1 infection. This study demonstrates the value of adjunctive neurological measures in large therapeutic trials of late HIV-1 infection.

KW - AIDS dementia complex

KW - Antiretroviral therapy

KW - CD4 T lymphocytes

KW - Central nervous system

KW - Didanosine

KW - Neuropsychological test

KW - Nevirapine

KW - Reverse transcriptase inhibitors

KW - Viral load

KW - Zalcitabine

KW - Zidovudine

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UR - http://www.scopus.com/inward/citedby.url?scp=16744362308&partnerID=8YFLogxK

U2 - 10.1097/00002030-199909100-00011

DO - 10.1097/00002030-199909100-00011

M3 - Article

C2 - 10509569

AN - SCOPUS:16744362308

VL - 13

SP - 1677

EP - 1685

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 13

ER -