Is long-term virological response related to CCR5 Delta32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?
OBJECTIVE
The aim of the study was to determine whether the chemokine (C-C motif) receptor 5 (CCR5) Delta32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1-infected patients.


METHODS
The genetic substudy of the Agence Nationale de Recherche sur le SIDA (ANRS) CO8 APROCO-COPILOTE cohort included 609 patients who started protease inhibitor-containing cART in 1997-1999. Patients were considered to have a sustained virological response if all plasma HIV RNA measurements in the period considered were <500 HIV-1 RNA copies/ml, allowing for a single blip. Virological response was compared between patients heterozygous for CCR5 Delta32 (Delta32/wt) and wild-type patients (wt/wt) from month 4 to year 3 and from month 4 to year 5. Logistic regression analysis was used to adjust for baseline demographical data, HIV RNA, CD4 cell count, antiretroviral exposure status, time spent on antiretroviral therapy at years 3 and 5 and adherence to treatment (month 4 to year 3 or 5).


RESULTS
A sustained virological response was more frequent in Delta32/wt than in wt/wt patients from month 4 to year 3, with 66%vs. 52% of patients, respectively, showing a sustained response (P=0.02); after adjustment for potential confounders, the association of Delta32 with a sustained response was nearly significant (P=0.07). A sustained virological response was also more frequent in Delta32/wt patients up to year 5, with 48% showing a sustained response vs. 35% of wt/wt patients (P=0.01); after adjustment, Delta32 remained significantly associated with a sustained virological response up to year 5 (P=0.04). There was no association with CD4 response.


CONCLUSIONS
The Delta32 deletion in Delta32/wt patients is associated with a beneficial virological response to cART in the long term. Whether this association is a direct effect of the Delta32 deletion remains unclear and requires confirmation in further observational studies.
Laurichesse
J-J
JJ
Laboratoire de Recherche en Pathologie Infectieuse, Université Paris 7, Paris, France. j-j.laurichesse@ch-mantes-la-jolie.fr
Taieb
A
A
Capoulade-Metay
C
C
Katlama
C
C
Villes
V
V
Drobacheff-Thiebaud
M-C
MC
Raffi
F
F
Chêne
G
G
Theodorou
I
I
Leport
C
C
D000328:Adult; D000367:Age Factors; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D005260:Female; D017353:Gene Deletion; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D016896:Treatment Outcome
D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019713:Receptors, CCR5