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Short communication. Association of the CCR5delta32 mutation with clinical response and >5-year survival following initiation of first triple antiretroviral regimen.
Antivir Ther. 2005; 10(7):849-53.AT

Abstract

OBJECTIVE

The CCR5delta32 mutation is associated with slower HIV disease progression in untreated infection. However, it remains controversial as to whether CCR5delta32 is a relevant prognostic marker in the context of highly active antiretroviral therapy (HAART). Here we investigate associations between CCR5delta32 and HAART outcomes in a large, population-based cohort of >1000 antiretroviral-naive individuals initiating triple therapy over a median >5 year follow-up.

METHODS

CCR5delta32 genotypes were determined using PCR and DNA sequencing in a cohort of 1188 antiretroviral-naive individuals initiating triple therapy in British Columbia. Associations between CCR5delta32 and baseline (pre-therapy) sociodemographic and clinical parameters were investigated in a cross-sectional analysis. Cox proportional hazards regression was used to investigate the effect of CCR5delta32 on clinical outcomes following therapy initiation. The endpoints that were evaluated included time to plasma viral load (pVL) suppression <400 copies HIV RNA/ml, subsequent time to pVL rebound > or =400 copies/ml, time to CD4+ cell decline below baseline, and time to non-accidental death over a median >5 year follow-up.

RESULTS

CCR5delta32 genotypes were available for 1174 of 1188 individuals (98.8%): 171 (14.6%) CCR5wt/delta32 and 1003 (85.4%) CCR5wt/wt. At baseline, CCR5wt/delta32 individuals had higher CD4+ cell counts (P=0.04), lower plasma viral loads (P=0.06) and were slightly older than CCR5wt/wt individuals (P=0.04). In multivariate analyses controlling for baseline parameters and adherence estimates, we observed a significant association between CCR5wt/delta32 and a shorter time to initial pVL suppression <400 copies/ml (multivariate hazard ratio [HR]: 1.20; 95% confidence interval [CI]: 1.01-1.44). No associations were observed between CCR5delta32 and other clinical outcomes including subsequent time to pVL rebound or time to CD4+ cell decline below baseline. In univariate analyses, we observed a significant association between CCR5wt/delta32 genotype and improved survival over the median >5 year period following initiation of HAART (P=0.03). However, this association did not remain significant in multivariate analyses after adjusting for baseline factors including adherence (multivariate HR: 0.64; 95% CI: 0.38-1.07; P=0.09)

CONCLUSION

Results indicate that, after controlling for adherence, the CCR5delta32 mutation is likely not a clinically significant predictor of longer-term clinical responses or survival in the context of HAART.

Authors+Show Affiliations

B.C. Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

16312181

Citation

Brumme, Zabrina L., et al. "Short Communication. Association of the CCR5delta32 Mutation With Clinical Response and >5-year Survival Following Initiation of First Triple Antiretroviral Regimen." Antiviral Therapy, vol. 10, no. 7, 2005, pp. 849-53.
Brumme ZL, Henrick BM, Brumme CJ, et al. Short communication. Association of the CCR5delta32 mutation with clinical response and >5-year survival following initiation of first triple antiretroviral regimen. Antivir Ther (Lond). 2005;10(7):849-53.
Brumme, Z. L., Henrick, B. M., Brumme, C. J., Hogg, R. S., Montaner, J. S., & Harrigan, P. R. (2005). Short communication. Association of the CCR5delta32 mutation with clinical response and >5-year survival following initiation of first triple antiretroviral regimen. Antiviral Therapy, 10(7), 849-53.
Brumme ZL, et al. Short Communication. Association of the CCR5delta32 Mutation With Clinical Response and >5-year Survival Following Initiation of First Triple Antiretroviral Regimen. Antivir Ther (Lond). 2005;10(7):849-53. PubMed PMID: 16312181.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Short communication. Association of the CCR5delta32 mutation with clinical response and >5-year survival following initiation of first triple antiretroviral regimen. AU - Brumme,Zabrina L, AU - Henrick,Bethany M, AU - Brumme,Chanson J, AU - Hogg,Robert S, AU - Montaner,Julio S G, AU - Harrigan,P Richard, PY - 2005/11/30/pubmed PY - 2006/8/22/medline PY - 2005/11/30/entrez SP - 849 EP - 53 JF - Antiviral therapy JO - Antivir. Ther. (Lond.) VL - 10 IS - 7 N2 - OBJECTIVE: The CCR5delta32 mutation is associated with slower HIV disease progression in untreated infection. However, it remains controversial as to whether CCR5delta32 is a relevant prognostic marker in the context of highly active antiretroviral therapy (HAART). Here we investigate associations between CCR5delta32 and HAART outcomes in a large, population-based cohort of >1000 antiretroviral-naive individuals initiating triple therapy over a median >5 year follow-up. METHODS: CCR5delta32 genotypes were determined using PCR and DNA sequencing in a cohort of 1188 antiretroviral-naive individuals initiating triple therapy in British Columbia. Associations between CCR5delta32 and baseline (pre-therapy) sociodemographic and clinical parameters were investigated in a cross-sectional analysis. Cox proportional hazards regression was used to investigate the effect of CCR5delta32 on clinical outcomes following therapy initiation. The endpoints that were evaluated included time to plasma viral load (pVL) suppression <400 copies HIV RNA/ml, subsequent time to pVL rebound > or =400 copies/ml, time to CD4+ cell decline below baseline, and time to non-accidental death over a median >5 year follow-up. RESULTS: CCR5delta32 genotypes were available for 1174 of 1188 individuals (98.8%): 171 (14.6%) CCR5wt/delta32 and 1003 (85.4%) CCR5wt/wt. At baseline, CCR5wt/delta32 individuals had higher CD4+ cell counts (P=0.04), lower plasma viral loads (P=0.06) and were slightly older than CCR5wt/wt individuals (P=0.04). In multivariate analyses controlling for baseline parameters and adherence estimates, we observed a significant association between CCR5wt/delta32 and a shorter time to initial pVL suppression <400 copies/ml (multivariate hazard ratio [HR]: 1.20; 95% confidence interval [CI]: 1.01-1.44). No associations were observed between CCR5delta32 and other clinical outcomes including subsequent time to pVL rebound or time to CD4+ cell decline below baseline. In univariate analyses, we observed a significant association between CCR5wt/delta32 genotype and improved survival over the median >5 year period following initiation of HAART (P=0.03). However, this association did not remain significant in multivariate analyses after adjusting for baseline factors including adherence (multivariate HR: 0.64; 95% CI: 0.38-1.07; P=0.09) CONCLUSION: Results indicate that, after controlling for adherence, the CCR5delta32 mutation is likely not a clinically significant predictor of longer-term clinical responses or survival in the context of HAART. SN - 1359-6535 UR - https://www.unboundmedicine.com/medline/citation/16312181/Short_communication__Association_of_the_CCR5delta32_mutation_with_clinical_response_and_>5_year_survival_following_initiation_of_first_triple_antiretroviral_regimen_ L2 - http://hivinsite.ucsf.edu/InSite?page=kb-03-02-09 DB - PRIME DP - Unbound Medicine ER -