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Is long‐term virological response related to CCR5 Δ32 deletion in HIV‐1‐infected patients started on highly active antiretroviral therapy?
Author(s) -
Laurichesse JJ,
Taieb A,
CapouladeMetay C,
Katlama C,
Villes V,
DrobacheffThiebaud MC,
Raffi F,
Chêne G,
Theodorou I,
Leport C
Publication year - 2010
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2009.00769.x
Subject(s) - medicine , cart , confounding , viral load , cohort , logistic regression , antiretroviral therapy , sida , human immunodeficiency virus (hiv) , gastroenterology , immunology , viral disease , mechanical engineering , engineering
Objective The aim of the study was to determine whether the chemokine (C‐C motif) receptor 5 (CCR5) Δ32 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 Δ32 (Δ32/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 Δ32/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 Δ32 with a sustained response was nearly significant ( P =0.07). A sustained virological response was also more frequent in Δ32/wt patients up to year 5, with 48% showing a sustained response vs . 35% of wt/wt patients ( P =0.01); after adjustment, Δ32 remained significantly associated with a sustained virological response up to year 5 ( P =0.04). There was no association with CD4 response. Conclusion The Δ32 deletion in Δ32/wt patients is associated with a beneficial virological response to cART in the long term. Whether this association is a direct effect of the Δ32 deletion remains unclear and requires confirmation in further observational studies.