title: Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS.
abstract: BACKGROUND
  The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown.
  
  
  RESULTS
  Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56-3.62, p<0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p<0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/µL; p = 0.001) even after adjusting for potential confounders.
  
  
  CONCLUSIONS
  In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution.
authors.affiliation: Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, United States of America. vcmarco@emory.edu
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Marconi
authors.forename: Greg
authors.initials: G
authors.lastname: Grandits
authors.forename: Jason F
authors.initials: JF
authors.lastname: Okulicz
authors.forename: Glenn
authors.initials: G
authors.lastname: Wortmann
authors.forename: Anuradha
authors.initials: A
authors.lastname: Ganesan
authors.forename: Nancy
authors.initials: N
authors.lastname: Crum-Cianflone
authors.forename: Michael
authors.initials: M
authors.lastname: Polis
authors.forename: Michael
authors.initials: M
authors.lastname: Landrum
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Dolan
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Ahuja
authors.forename: Brian
authors.initials: B
authors.lastname: Agan
authors.forename: Hemant
authors.initials: H
authors.lastname: Kulkarni
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000821:virology; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012698:Serologic Tests; D016896:Treatment Outcome; D019562:Viral Load