title: Determinants of sustainable CD4 lymphocyte count increases in response to antiretroviral therapy.
abstract: OBJECTIVE
  HIV-induced CD4 lymphocyte depletion is partially reversed by antiretroviral therapy but it is unclear if the degree to which the CD4 count rises depends on viral suppression (if so, the extent of viral suppression required to achieve a maximal CD4 count rise), whether the rise is sustainable and whether it occurs in patients with CD4 count <10 x 10(6) cells/l. We aimed to address these issues.
  
  
  METHODS
  We studied CD4 count and plasma HIV RNA values every 4 weeks for 72 weeks in 154 patients starting indinavir-containing regimens.
  
  
  RESULTS
  Mean baseline HIV RNA and CD4 count were 4.8 log10 copies/ml and 180 x 10(6) cells/l, respectively. Overall, there was a mean increase in CD4 count of 143 x 10(6) cells/l by 72 weeks. The adjusted mean increase (adjusted for initial viral load, CD4 count and age) was strongly related to the mean viral suppression over the follow-up period (P < 0.0001). Importantly, there was a highly significant difference (P = 0.0004) in the rise in CD4 count between those with 2-3 log suppression (161 x 10(6) cells/l) and those with > 3 log suppression (314 x 10(6) cells/l; mean 3.6 log suppression in this group), suggesting that with even greater suppression the rise in CD4 lymphocytes may be still larger. We also studied whether CD4 counts were still rising after 72 weeks in patients with sustained suppression of at least 3 log in viral load. There was a significant (P = 0.004; paired t-test) rise in count of 43 x 10(6) cells/l between weeks 64 and 72 in these patients, suggesting that regeneration continues at least up to 72 weeks after therapy, provided virus replication continues to be suppressed. Patients with initial CD4 counts < 10 x 10(6) cells/l experienced no smaller rises than those at higher levels, even after adjustment for other factors.
  
  
  CONCLUSIONS
  These results strongly support a direct causal relationship between HIV replication and CD4 lymphocyte count depletion. The rise in those with > 3 log suppression provides the best available indicator of the potential for natural CD4 regeneration in HIV-infected patients. However, since still greater CD4 count rises may be seen with more suppressive regimens, it may not be possible to study the intrinsic CD4 regenerative capacity until such regimens are available.
authors.affiliation: Department of Infectious Diseases, Klinikum der Johann Wofgang Goethe-Universitat, Medizinische Klinik, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Staszewski
authors.forename: V
authors.initials: V
authors.lastname: Miller
authors.forename: C
authors.initials: C
authors.lastname: Sabin
authors.forename: C
authors.initials: C
authors.lastname: Schlecht
authors.forename: P
authors.initials: P
authors.lastname: Gute
authors.forename: S
authors.initials: S
authors.lastname: Stamm
authors.forename: T
authors.initials: T
authors.lastname: Leder
authors.forename: A
authors.initials: A
authors.lastname: Berger
authors.forename: E
authors.initials: E
authors.lastname: Weidemann
authors.forename: A
authors.initials: A
authors.lastname: Hill
authors.forename: A
authors.initials: A
authors.lastname: Phillips
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir