OBJECTIVES: To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. METHODS:RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. RESULTS: Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL. CONCLUSIONS: At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.
RCT Entities:
OBJECTIVES: To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. METHODS: RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. RESULTS: Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL. CONCLUSIONS: At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.
Authors: Steven G Deeks; Rebecca Hoh; Robert M Grant; Terri Wrin; Jason D Barbour; Amy Narvaez; Denise Cesar; Ken Abe; Mary Beth Hanley; Nicholas S Hellmann; Christos J Petropoulos; Joseph M McCune; Marc K Hellerstein Journal: J Infect Dis Date: 2002-01-17 Impact factor: 5.226
Authors: J Carbone; J Gil; J M Benito; J Navarro; A Muñóz-Fernández; J Bartolomé; J M Zabay; F López; E Fernández-Cruz Journal: AIDS Date: 2000-12-22 Impact factor: 4.177
Authors: C J Petropoulos; N T Parkin; K L Limoli; Y S Lie; T Wrin; W Huang; H Tian; D Smith; G A Winslow; D J Capon; J M Whitcomb Journal: Antimicrob Agents Chemother Date: 2000-04 Impact factor: 5.191
Authors: S G Deeks; T Wrin; T Liegler; R Hoh; M Hayden; J D Barbour; N S Hellmann; C J Petropoulos; J M McCune; M K Hellerstein; R M Grant Journal: N Engl J Med Date: 2001-02-15 Impact factor: 91.245
Authors: Guido Silvestri; Donald L Sodora; Richard A Koup; Mirko Paiardini; Shawn P O'Neil; Harold M McClure; Silvija I Staprans; Mark B Feinberg Journal: Immunity Date: 2003-03 Impact factor: 31.745
Authors: Ana E Sousa; Jorge Carneiro; Martin Meier-Schellersheim; Zvi Grossman; Rui M M Victorino Journal: J Immunol Date: 2002-09-15 Impact factor: 5.422