Innate Antibacterial Activity in Female Genital Tract Secretions Is Associated with Increased Risk of HIV Acquisition

Rebecca Pellett Madan, Lindi Masson, Jessica Tugetman, Lise Werner, Anneke Grobler, Koleka Mlisana, Yungtai Lo, Denise Che, Kelly B. Arnold, Salim S Abdool Karim, Jo Ann S Passmore, Betsy Herold

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13 Scopus citations

Abstract

Greater inhibitory activity against Escherichia coli and levels of human β defensin (HBD)-2 in genital tract secretions predicted HIV acquisition in women in the HPTN 035 trial. We investigated whether higher levels of E. coli inhibitory activity and antimicrobial peptides in cervicovaginal lavage (CVL) samples predicted HIV acquisition in women in the CAPRISA 002 Acute Infection Study. E. coli inhibitory activity and antimicrobial peptides were quantified in CVL from a subset of CAPRISA 002 participants who did not seroconvert (n=39) and from seroconverting women prior to infection (n=17) and during acute infection (n=11). Women who acquired HIV had significantly greater preinfection CVL E. coli inhibitory activity (p=0.01) and HBD-1 levels (p=0.02) compared to women who remained uninfected. Preinfection E. coli inhibitory activity remained significantly associated with seroconversion following adjustment for the presence of bacterial vaginosis (OR 1.45; 95% CI 1.07, 1.97). Partial least squares discriminant analysis confirmed that preinfection CVL E. coli inhibitory activity, together with higher CVL concentrations of HBD-1 and secretory leukocyte protease inhibitor, distinguished seroconverters from nonseroconverters with 67% calibration accuracy. CVL concentrations of human neutrophil peptides (HNP) 1-3 increased significantly with acute infection (p=0.001) and correlated with plasma viral set point (r=0.66, p=0.03). E. coli inhibitory activity in genital tract secretions could provide a biomarker of HIV risk. The correlation between HNP 1-3 and viral set point merits further investigation of the relationship between mucosal inflammation during early HIV infection and disease progression.

Original languageEnglish (US)
Pages (from-to)1153-1159
Number of pages7
JournalAIDS Research and Human Retroviruses
Volume31
Issue number11
DOIs
StatePublished - Nov 1 2015

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ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Cite this

Pellett Madan, R., Masson, L., Tugetman, J., Werner, L., Grobler, A., Mlisana, K., Lo, Y., Che, D., Arnold, K. B., Karim, S. S. A., Passmore, J. A. S., & Herold, B. (2015). Innate Antibacterial Activity in Female Genital Tract Secretions Is Associated with Increased Risk of HIV Acquisition. AIDS Research and Human Retroviruses, 31(11), 1153-1159. https://doi.org/10.1089/aid.2015.0011