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. CONCLUSION: 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.