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

Objective: In a large multi-center clinical trial of combination reverse tr anscriptase inhibitors (RTIs), we assessed the impact of antiretroviral the rapy on neurological function, the relationship between neurological and sy stemic benefit, and the prognostic value of neurological performance in lat e 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 Hemo philia Foundation sites Patients: Adult HIV-infected patients (n = 1313) with CD4 counts < 50 x 10( 6) cells/l. Interventions: Four combinations of reverse transcriptase inhibitors consis ting 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 quantitativ e neurological performance battery score, the QNPZ-4, administered to 1031 subjects. Results: Triple therapy and ZDV/ddl combination preserved or improved neuro logical 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 concentratio ns. Conclusions: Combination antiretroviral therapy can have a salutary effect on preserving or improving neurological function. Superior systemic treatme nts may likewise better preserve neurological function. The significant ass ociation of poor neurological performance with mortality, independent of CD 4 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 infecti on. This study demonstrates the value of adjunctive neurological measures i n large therapeutic trials of late HIV-1 infection. (C) 1999 Lippincott Wil liams & Wilkins.