Risk of breast cancer with CXCR4-using HIV defined by V3 loop sequencing

James J. Goedert, Luke C. Swenson, Laura A. Napolitano, Mojgan Haddad, Kathryn Anastos, Howard Minkoff, Mary Young, Alexandra Levine, Oluwatoyin Adeyemi, Eric C. Seaberg, Bradley Aouizerat, Charles S. Rabkin, P. Richard Harrigan, Nancy A. Hessol

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Abstract

Objective: Evaluate the risk of female breast cancer associated with HIV-CXCR4 (X4) tropism as determined by various genotypic measures. Methods: A breast cancer case-control study, with pairwise comparisons of tropism determination methods, was conducted. From the Women's Interagency HIV Study repository, one stored plasma specimen was selected from 25 HIV-infected cases near the breast cancer diagnosis date and 75 HIV-infected control women matched for age and calendar date. HIV-gp120 V3 sequences were derived by Sanger population sequencing (PS) and 454-pyro deep sequencing (DS). Sequencingbased HIV-X4 tropism was defined using the geno2pheno algorithm, with both high-stringency DS [false-positive rate (3.5) and 2% X4 cutoff], and lower stringency DS (false-positive rate, 5.75 and 15% X4 cutoff). Concordance of tropism results by PS, DS, and previously performed phenotyping was assessed with kappa (k) statistics. Case-control comparisons used exact P values and conditional logistic regression. Results: In 74 women (19 cases, 55 controls) with complete results, prevalence of HIV-X4 by PS was 5% in cases vs 29% in controls (P = 0.06; odds ratio, 0.14; confidence interval: 0.003 to 1.03). Smaller case-control prevalence differences were found with highstringency DS (21% vs 36%, P = 0.32), lower stringency DS (16% vs 35%, P = 0.18), and phenotyping (11% vs 31%, P = 0.10). HIVX4 tropism concordance was best between PS and lower stringency DS (93%, k = 0.83). Other pairwise concordances were 82%-92% (k = 0.56-0.81). Concordance was similar among cases and controls. Conclusions: HIV-X4 defined by population sequencing (PS) had good agreement with lower stringency DS and was significantly associated with lower odds of breast cancer..

Original languageEnglish (US)
Pages (from-to)30-35
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2015

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Keywords

  • AIDS
  • Breast cancer
  • Chemokine receptors
  • HIV
  • Parallel sequencing
  • Women

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Goedert, J. J., Swenson, L. C., Napolitano, L. A., Haddad, M., Anastos, K., Minkoff, H., Young, M., Levine, A., Adeyemi, O., Seaberg, E. C., Aouizerat, B., Rabkin, C. S., Richard Harrigan, P., & Hessol, N. A. (2015). Risk of breast cancer with CXCR4-using HIV defined by V3 loop sequencing. Journal of Acquired Immune Deficiency Syndromes, 68(1), 30-35. https://doi.org/10.1097/QAI.0000000000000400