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

Richard W. Price; Constantin T. 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. Kapoor; K. 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; K. 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

doi:10.1097/00002030-199909100-00011

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

Richard W. Price, Constantin T. 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, K. 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

Vagelos College of Physicians and Surgeons

Research output: Contribution to journal › Article › peer-review

124 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 language	English
Pages (from-to)	1677-1685
Number of pages	9
Journal	AIDS
Volume	13
Issue number	13
DOIs	https://doi.org/10.1097/00002030-199909100-00011
Publication status	Published - 1999

Funding

Funders	Funder number
National Institute of Allergy and Infectious Diseases	U01AI038855
National Institute of Neurological Disorders and Stroke	P01NS025701

ASJC Scopus Subject Areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1097/00002030-199909100-00011

Cite this

Price, R. W., Yiannoutsos, C. T., Clifford, D. B., Zaborski, L., Tselis, A., Sidtis, J. J., Cohen, B., Hall, C. D., Erice, A., Henry, K., Glicksman, M., Powderly, W. G., Swindells, S., Rudberg, G., Cooper, C., Kessler, H., Borucki, M., Galatas, P., Van der Horst, C., ... Kenton, A. (1999). Neurological outcomes in late HIV infection: Adverse impact of neurological impairment on survival and protective effect of antiviral therapy. AIDS, 13(13), 1677-1685. https://doi.org/10.1097/00002030-199909100-00011

Price, RW, Yiannoutsos, CT, 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

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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.",

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

year = "1999",

doi = "10.1097/00002030-199909100-00011",

language = "English",

volume = "13",

pages = "1677--1685",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins",

number = "13",

}

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 T.

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, K.

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.

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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

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AN - SCOPUS:16744362308

SN - 0269-9370

VL - 13

SP - 1677

EP - 1685

JO - AIDS

JF - AIDS

IS - 13

ER -

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

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UN SDGs

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