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 10(6) 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.
RCT Entities:
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-infectedpatients (n = 1313) with CD4 counts < 50 x 10(6) 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.
Authors: Justin C McArthur; Norman Haughey; Suzanne Gartner; Kathy Conant; Carlos Pardo; Avi Nath; Ned Sacktor Journal: J Neurovirol Date: 2003-04 Impact factor: 2.643
Authors: Lakshmanan Annamalai; Veena Bhaskar; Douglas R Pauley; Heather Knight; Kenneth Williams; Margaret Lentz; Eva Ratai; Susan V Westmoreland; R Gilberto González; Shawn P O'Neil Journal: Am J Pathol Date: 2010-07-01 Impact factor: 4.307
Authors: Taylor Kuhn; Philip Sayegh; Jacob D Jones; Jason Smith; Manoj K Sarma; A Ragin; Elyse J Singer; M Albert Thomas; April D Thames; Steven A Castellon; Charles H Hinkin Journal: J Neurovirol Date: 2017-05-30 Impact factor: 2.643
Authors: Lars Hagberg; Paola Cinque; Magnus Gisslen; Bruce J Brew; Serena Spudich; Arabella Bestetti; Richard W Price; Dietmar Fuchs Journal: AIDS Res Ther Date: 2010-06-03 Impact factor: 2.250
Authors: Edward R Hammond; Rosa M Crum; Glenn J Treisman; Shruti H Mehta; Christina M Marra; David B Clifford; Susan Morgello; David M Simpson; Benjamin B Gelman; Ronald J Ellis; Igor Grant; Scott L Letendre; Justin C McArthur Journal: Am J Epidemiol Date: 2014-06-24 Impact factor: 4.897
Authors: Sriram Venneti; Brian J Lopresti; Guoji Wang; Stephanie J Bissel; Chester A Mathis; Carolyn C Meltzer; Fernando Boada; Saverio Capuano; Geraldine J Kress; Denise K Davis; James Ruszkiewicz; Ian J Reynolds; Michael Murphey-Corb; Anita M Trichel; Stephen R Wisniewski; Clayton A Wiley Journal: J Clin Invest Date: 2004-04 Impact factor: 14.808