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

J Acquir Immune Defic Syndr. 2015 Jan 1;68(1):30-5. doi: 10.1097/QAI.0000000000000400.


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). Sequencing-based 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 (κ) 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 high-stringency DS (21% vs 36%, P = 0.32), lower stringency DS (16% vs 35%, P = 0.18), and phenotyping (11% vs 31%, P = 0.10). HIV-X4 tropism concordance was best between PS and lower stringency DS (93%, κ = 0.83). Other pairwise concordances were 82%-92% (κ = 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Breast Neoplasms / complications
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease*
  • HIV / genetics
  • HIV / physiology*
  • HIV Infections / complications*
  • Humans
  • Middle Aged
  • Receptors, CXCR4 / genetics*


  • CXCR4 protein, human
  • Receptors, CXCR4