title: Determinants of response to first HAART regimen in antiretroviral-naïve patients with an estimated time since HIV seroconversion.
abstract: OBJECTIVE
  To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naïve patients, adjusting for time since HIV-1 seroconversion.
  
  
  METHODS
  Data from HIV-cohort studies where dates of seroconversion have been reliably estimated. Methods In previously untreated patients, short- and long-term marker responses from HAART initiation (three or more antiretroviral drugs) to the end of follow-up or any treatment modification were considered using mixed effects models accounting for undetectable HIV viral load and informative dropout.
  
  
  RESULTS
  In total, 943 patients were treated with a first HAART regimen for a median of 29 months. In adjusted analyses, compared with a reference group of homosexual men without AIDS initiating treatment 4 years after seroconversion, injecting drug users (IDUs) were treated at similar CD4 and HIV RNA levels but had poorer short-term virological response (2.54 vs 2.13 log(10) HIV-1 RNA copies/mL at 1.5 months, P=0.03) and poorer long-term immunological response (522 vs 631 cells/microL at 24 months, P<0.0001). Although individuals with AIDS at HAART initiation had lower CD4 counts (206 vs 382 cells/microL, P<0.0001), their immunological responses were similar to those of individuals without AIDS. Similarly, individuals further from seroconversion started HAART at lower CD4 counts (e.g. 311 vs 382 cells/microL at vs before 9 years from seroconversion, P<0.0001), but had similar CD4 responses. However, they experienced poorer long-term virological response (0.67 log(10) copies/mL/year smaller decline, P<0.0001) compared to those treated before 9 years from seroconversion.
  
  
  CONCLUSIONS
  Taking into account the time elapsed since seroconversion, this study suggests that careful choices of initial treatment should be made and intensive follow-up carried out in high-risk subgroups such as IDUs who have poorer responses.
authors.affiliation: INSERM E0338 Biostatistics, Bordeaux 2 University, Bordeaux, France. rodolphe.thiebaut@isped.u-bordeaux2.fr
authors.forename: R
authors.initials: R
authors.lastname: Thiébaut
authors.forename: H
authors.initials: H
authors.lastname: Jacqmin-Gadda
authors.forename: S
authors.initials: S
authors.lastname: Walker
authors.forename: C
authors.initials: C
authors.lastname: Sabin
authors.forename: M
authors.initials: M
authors.lastname: Prins
authors.forename: J
authors.initials: J
authors.lastname: Del Amo
authors.forename: K
authors.initials: K
authors.lastname: Porter
authors.forename: F
authors.initials: F
authors.lastname: Dabis
authors.forename: G
authors.initials: G
authors.lastname: Chêne
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral