Relationship between antiretrovirals used as part of a cART regimen and CD4 cell count increases in patients with suppressed viremia.
BACKGROUND
It is unknown if the CD4 cell count response differs according to antiretroviral drugs used in combination antiretroviral therapy (cART) in patients with maximal virological suppression [viral load (VL) < 50 copies/ml].


OBJECTIVE
To compare the change in CD4 cell count over consecutive measurements with VL < 50 copies/ml at both time-points according to nucleoside backbones and other antiretrovirals used.


METHODS
Generalized linear models, accounting for multiple measurements within patients, were used to compare CD4 cell count changes after adjustment for antiretrovirals, time from starting cART, age, CD4 at first VL < 50 copies/ml, prior antiretroviral treatment, and change in CD4 cell count since starting cART.


RESULTS
We studied 28418 instances of VL < 50 copies/ml in 4041 patients. The mean annual change in CD4 cell count was +45.5/microl [95% confidence interval (CI) +39.4 to +51.6/microl). Comparing two drug nucleoside backbones, there was a lower annual change in CD4 cell count for zidovudine/lamivudine (n = 13038; -15.4/microl; P = 0.012) and for those on tenofovir (n = 1809; -27.3/microl; P = 0.029) compared to lamivudine/stavudine (n = 7339). Compared to the boosted-protease inhibitor regimen (n = 5915), use of an abacavir-based triple-nucleoside regimen was associated with a lower annual change in CD4 cell count (n = 2504 pairs; -26.1/microl; P = 0.011).


CONCLUSIONS
A nucleoside backbone of zidovudine/lamivudine or any tenofovir-based backbone was associated with significantly poorer increases in CD4 cell count compared to a nucleoside backbone of stavudine/lamivudine, as was an abacavir-based triple nucleoside regimen compared to a boosted protease inhibitor regimen. Long-term studies are needed to determine whether the differences in immunological response seen here translate into differences in the risk of clinical disease.
Mocroft
Amanda
A
Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK. a.mocroft@pcps.ucl.ac.uk
Phillips
Andrew N
AN
Ledergerber
Bruno
B
Katlama
Christine
C
Chiesi
Antonio
A
Goebel
Frank-Detlef
FD
Knysz
Brygioa
B
Antunes
Francisco
F
Reiss
Peter
P
Lundgren
Jens D
JD
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D000068698:Tenofovir; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D000068698:Tenofovir; D000225:Adenine