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

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


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
Pages (from-to)1677-1685
Number of pages9
Issue number13
StatePublished - 1999


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


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