title: Decline of CD4⁺ T-cell count before start of therapy and immunological response to treatment in antiretroviral-naive individuals.
abstract: OBJECTIVE
  Treatment guidelines recommend initiation of therapy for individuals experiencing rapid CD4 cell decline. It is not known, however, whether the rate of CD4 cell decline before combination antiretroviral therapy (cART) is related to immunological response following cART.
  
  
  METHODS
  We estimated precART and postcART CD4 cell slopes by mixed models and categorized patients into two groups according to whether estimated precART slopes were above or below the 75th percentile. We compared immunological responses of the two groups through both mixed models and survival techniques. Models were stratified by CD4 cell at baseline, adjusted for HIV RNA, age, sex, HIV transmission group, year of seroconversion, initiation during primary infection, hepatitis C virus and hepatitis B virus serostatus, and cART class.
  
  
  RESULTS
  Of 2038 eligible patients, 1531 and 507 experienced median (interquartile range) precART CD4 cell slope of −105 (−471 to −61) and −42 (−62 to −80) cells/μl, respectively, over 2 years. After adjusting for potential confounders, individuals with shallower decline experienced a slower rate of CD4 cell recovery following cART initiation of +9.5 [95% confidence interval (CI) +6.6 to +12.2] compared to +13.9 (+13.0 to +14.8) cells/μl per month among those with steeper precART decline (P < 0.001). After stratifying by the baseline CD4 cell count, the adjusted relative hazard of an increase from baseline of more than 50 cells/μl was 0.70 (95% CI 0.62−0.79) for those with a shallower vs. steeper precART decline.
  
  
  CONCLUSIONS
  Findings highlight the existence of a subgroup of individuals with shallower precART CD4 cell decline who experience poorer CD4 cell increases after cART; new studies in this group may provide information to optimize responses to therapy.
authors.affiliation: Clinic of Infectious Diseases, Modena University, Modena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.forename: Heiner C
authors.initials: HC
authors.lastname: Bucher
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rezza
authors.forename: Kholoud
authors.initials: K
authors.lastname: Porter
authors.forename: Maria
authors.initials: M
authors.lastname: Dorrucci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001315:Australia; D018791:CD4 Lymphocyte Count; D002170:Canada; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D012367:RNA, Viral; D019562:Viral Load; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral