Is long-term virological response related to CCR5 32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?

• Published in: HIV medicine Vol. 11; no. 4; pp. 239 - 244
• Main Authors: Laurichesse, J-J, Taieb, A, Capoulade-Metay, C, Katlama, C, Villes, V, Drobacheff-Thiebaud, M-C, Raffi, F, Chene, G, Theodorou, I, Leport, C
• Format: Journal Article
• Language: English
• Published: 01-04-2010
• Subjects: Human immunodeficiency virus 1
• ISSN: 1464-2662
• DOI: 10.1111/j.1468-1293.2009.00769.x

ObjectiveThe aim of the study was to determine whether the chemokine (C-C motif) receptor 5 (CCR5) 32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1-infected patients.MethodsThe 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 32 (32-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).ResultsA sustained virological response was more frequent in 32-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 32 with a sustained response was nearly significant (P=0.07). A sustained virological response was also more frequent in 32-wt patients up to year 5, with 48% showing a sustained response vs. 35% of wt-wt patients (P=0.01); after adjustment, 32 remained significantly associated with a sustained virological response up to year 5 (P=0.04). There was no association with CD4 response.ConclusionThe 32 deletion in 32-wt patients is associated with a beneficial virological response to cART in the long term. Whether this association is a direct effect of the 32 deletion remains unclear and requires confirmation in further observational studies.