Neurological outcomes in late HIV infection: adverse impact of neurological impairment on survival and protective effect of antiviral therapy. AIDS Clinical Trial Group and Neurological AIDS Research Consortium study team.
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.


METHODS
Neurological evaluations incorporated in a randomized, multi-center trial of combination antiretroviral therapy.


METHODS
Forty-two AIDS Clinical Trials Group sites and seven National Hemophilia Foundation sites.


METHODS
Adult HIV-infected patients (n = 1313) with CD4 counts < 50 x 10(6) cells/l.


METHODS
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.


METHODS
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.
Price
R W
RW
University of California, San Francisco, USA.
Yiannoutsos
C T
CT
Clifford
D B
DB
Zaborski
L
L
Tselis
A
A
Sidtis
J J
JJ
Cohen
B
B
Hall
C D
CD
Erice
A
A
Henry
K
K
D015526:AIDS Dementia Complex / Q000175:diagnosis; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000401:mortality* / Q000523:psychology*; D015497:HIV-1; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011379:Prognosis
D019380:Anti-HIV Agents