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Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals.
J Infect Dis. 2005 Aug 01; 192(3):466-74.JI

Abstract

OBJECTIVE

We wished to characterize the epidemiological and clinical correlates of CXCR4-using human immunodeficiency virus type 1 (HIV-1) ("X4 variants") in a cross-sectional analysis of a large population of antiretroviral-naive individuals.

METHODS

HIV-1 coreceptor use was determined in the last pretherapy plasma sample for 1191 individuals initiating triple-combination therapy in British Columbia, Canada. Baseline variables investigated included sociodemographic characteristics, plasma viral load (pVL), CD4 cell count, AIDS diagnosis, HIV-1 V3 loop sequence, and human CCR5 Delta 32 genotype.

RESULTS

Individuals harboring X4 variants (n = 178 of 979 phenotyped samples; 18.2%) displayed a poorer baseline clinical profile than individuals harboring exclusively CCR5-using HIV-1 ("R5 variants") (median pVL, 175,000 vs. 120,000 copies of HIV-1 RNA/mL [P = .0006]; median CD4 cell count, 110 vs. 290 cells/mm(3) [P < .0001]). Individuals heterozygous for the CCR5 Delta 32 deletion (n = 128 of 967; 13.2%) were at 2.5 times higher risk of harboring X4 variants, compared with those without the deletion (multivariate P = .0005). The presence of basic amino acids at codon 11 and/or codon 25 of HIV-1 V3 (n = 109 of 955; 11.4%) was associated with a 9.1 times higher risk of harboring X4 variants (multivariate P < .0001), regardless of CCR5 Delta 32 genotype. In multivariate analyses adjusting for baseline parameters, HIV-1 coreceptor use was not found to be a significant predictor of survival or treatment response.

CONCLUSION

Baseline CD4 cell count, pVL, HIV-1 V3 sequence, and CCR5 Delta 32 genotype were the strongest determinants of CXCR4-using HIV-1 in this population. After adjustment for baseline parameters, the presence of X4 variants before initiation of highly active antiretroviral therapy was not independently associated with a poorer outcome of therapy.

Authors+Show Affiliations

BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, and Faculty of Medicine, University of British Columbia, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15995960

Citation

Brumme, Zabrina L., et al. "Molecular and Clinical Epidemiology of CXCR4-using HIV-1 in a Large Population of Antiretroviral-naive Individuals." The Journal of Infectious Diseases, vol. 192, no. 3, 2005, pp. 466-74.
Brumme ZL, Goodrich J, Mayer HB, et al. Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals. J Infect Dis. 2005;192(3):466-74.
Brumme, Z. L., Goodrich, J., Mayer, H. B., Brumme, C. J., Henrick, B. M., Wynhoven, B., Asselin, J. J., Cheung, P. K., Hogg, R. S., Montaner, J. S., & Harrigan, P. R. (2005). Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals. The Journal of Infectious Diseases, 192(3), 466-74.
Brumme ZL, et al. Molecular and Clinical Epidemiology of CXCR4-using HIV-1 in a Large Population of Antiretroviral-naive Individuals. J Infect Dis. 2005 Aug 1;192(3):466-74. PubMed PMID: 15995960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals. AU - Brumme,Zabrina L, AU - Goodrich,James, AU - Mayer,Howard B, AU - Brumme,Chanson J, AU - Henrick,Bethany M, AU - Wynhoven,Brian, AU - Asselin,Jerome J, AU - Cheung,Peter K, AU - Hogg,Robert S, AU - Montaner,Julio S G, AU - Harrigan,P Richard, Y1 - 2005/06/23/ PY - 2004/11/24/received PY - 2005/03/03/accepted PY - 2005/7/5/pubmed PY - 2005/9/24/medline PY - 2005/7/5/entrez SP - 466 EP - 74 JF - The Journal of infectious diseases JO - J. Infect. Dis. VL - 192 IS - 3 N2 - OBJECTIVE: We wished to characterize the epidemiological and clinical correlates of CXCR4-using human immunodeficiency virus type 1 (HIV-1) ("X4 variants") in a cross-sectional analysis of a large population of antiretroviral-naive individuals. METHODS: HIV-1 coreceptor use was determined in the last pretherapy plasma sample for 1191 individuals initiating triple-combination therapy in British Columbia, Canada. Baseline variables investigated included sociodemographic characteristics, plasma viral load (pVL), CD4 cell count, AIDS diagnosis, HIV-1 V3 loop sequence, and human CCR5 Delta 32 genotype. RESULTS: Individuals harboring X4 variants (n = 178 of 979 phenotyped samples; 18.2%) displayed a poorer baseline clinical profile than individuals harboring exclusively CCR5-using HIV-1 ("R5 variants") (median pVL, 175,000 vs. 120,000 copies of HIV-1 RNA/mL [P = .0006]; median CD4 cell count, 110 vs. 290 cells/mm(3) [P < .0001]). Individuals heterozygous for the CCR5 Delta 32 deletion (n = 128 of 967; 13.2%) were at 2.5 times higher risk of harboring X4 variants, compared with those without the deletion (multivariate P = .0005). The presence of basic amino acids at codon 11 and/or codon 25 of HIV-1 V3 (n = 109 of 955; 11.4%) was associated with a 9.1 times higher risk of harboring X4 variants (multivariate P < .0001), regardless of CCR5 Delta 32 genotype. In multivariate analyses adjusting for baseline parameters, HIV-1 coreceptor use was not found to be a significant predictor of survival or treatment response. CONCLUSION: Baseline CD4 cell count, pVL, HIV-1 V3 sequence, and CCR5 Delta 32 genotype were the strongest determinants of CXCR4-using HIV-1 in this population. After adjustment for baseline parameters, the presence of X4 variants before initiation of highly active antiretroviral therapy was not independently associated with a poorer outcome of therapy. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/15995960/Molecular_and_clinical_epidemiology_of_CXCR4_using_HIV_1_in_a_large_population_of_antiretroviral_naive_individuals_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/431519 DB - PRIME DP - Unbound Medicine ER -