Improved virological response to highly active antiretroviral therapy in HIV-1-infected patients carrying the CCR5 Delta32 deletion.
BACKGROUND
Patients heterozygous for the C-C chemokine receptor 5 (CCR5) Delta32 deletion spontaneously progress less rapidly to AIDS and death than do wild-type patients. We investigated whether the CCR5 Delta32 deletion has an impact on immunological, virological and clinical responses to highly active antiretroviral therapy (HAART) in HIV-1-infected patients.


METHODS
We included in the study 565 HIV-1-infected patients from the French HIV-1 infected cohort with documented date of seroconversion (SEROCO)/haemophiliacs HIV-1 infected (HEMOCO) cohorts, who started HAART after 1996. We investigated virological responses to HAART at 6 months (defined as a plasma HIV-1 RNA measurement below the threshold of detection or a 2 log HIV-1 RNA decrease) and at 12 months (defined as a plasma HIV-1 RNA measurement below the threshold of detection) and clinical response to HAART by Kaplan-Meier survival curves, with AIDS and death as outcomes.


RESULTS
The Delta32 heterozygous patients (n=83; 15%) had a better virological response to HAART than wild-type patients (73 vs 53% at 6 months, P=0.01; and 60 vs 44% at 12 months, P=0.01). This better virological response was still observed after adjustment for antiretroviral status (whether or not patients were naïve to antiretroviral therapy), year of HAART initiation, number of new antiretroviral drugs and baseline viral load. There was no statistical difference between heterozygous patients and wild-type patients in terms of survival and AIDS-free survival.


CONCLUSIONS
CCR5 Delta32 heterozygous patients were more likely to have a virological response to HAART than wild-type patients at 6 and 12 months. However, this virological response did not produce better immunological and clinical responses. The long-term impact of the Delta32 deletion on survival in HIV-1-infected treated patients should be investigated in a meta-analysis.
Laurichesse
J J
JJ
INSERM, U569, Hôpital Bicêtre, Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France. jean-jacques.laurichesse@bch.aphp.fr
Persoz
A
A
Theodorou
I
I
Rouzioux
C
C
Delfraissy
J F
JF
Meyer
L
L
D000328:Adult; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D019562:Viral Load
D012367:RNA, Viral; D019713:Receptors, CCR5; D004247:DNA