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CCR5 D32 Deletion and Response to HAART in HIV-1-Infected Patients S. GUERIN*1, L. MEYER1, I. THEODOROU2, F. BOUFASSA1, M. MAGIEROWSKA2, C. GOUJARD3, C. ROUZIOUX4, P. DEBRE2, J. F. DELFRAISSY3, and SEROCO/HEMOCO Study Group.
1INSERM U292, Le Kremlin-Bicêtre; 2Hosp. Pitié Salpêtrière, Paris; 3Hosp. Bicêtre, Le Kremlin-Bicêtre; and 4Hosp. Necker, Paris, France Background: Patients bearing a D32 deletion on one allele of the gene coding for the CCR5 chemokine receptor progress less rapidly to AIDS and death than do wild-type patients.
Objective: To investigate the role of the CCR5 D32 deletion in the 6-month response to HAART in a protease inhibitor-naive population of HIV-1 infected patients.
Design: Prospective cohort study.
Patients: 166 protease inhibitor-naive patients from the SEROCO and HEMOCO cohorts who received a triple drug combination therapy including a protease inhibitor.
Outcome measures: A six-month response to HAART comprised a virological response, defined as at least one plasma HIV-1 RNA measurement below the threshold of 500 copies/ml or a two log HIV-1 RNA decrease, and an immunological response, defined as an increase of at least 50 CD4+ cells/mL.
Results: A six month response to HAART was observed in 53% of patients. The D32 heterozygous patients responded to HAART more often than wild-type patients, whichever type of response: immunological (91% versus 67%, p=0.021), virological (91% versus 65%, p=0.016) and immunological plus virological response (82% versus 49%, p=0.004). In a multivariate logistic analysis, the CCR5 genotype remained predictive of response to HAART, independently of potential confounding factors such as the type of protease inhibitor used in HAART and the number of previous antiretroviral regimens (aOR=4.7, p=0.011). A higher proportion of responders to HAART was again observed among D32 heterozygous patients at 12 months after adjustment (D32/wt versus wt/wt, aOR=3.7, p=0.019).
Conclusions: CCR5 D32 heterozygous patients are more likely to respond to HAART than wild-type patients. CCR5 genotyping could therefore become a useful tool in clinical practice, in order to refine the therapeutic management of HIV-1 infected patients.
Key Words: CCR5, Response to HAART
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