Background: The host immune response against mucosally acquired pathogens may be influenced by the mucosal immune milieu during acquisition. As Neisseria gonorrhoeae can impair dendritic cell and T-cell immune function, we hypothesized that coinfection during HIV acquisition would impair subsequent systemic T-cell responses.
Methods: Monthly screening for sexually transmitted infections was performed in high risk, HIV seronegative Kenyan female sex workers as part of an HIV prevention trial. Early HIV-specific CD8 T-cell responses and subsequent HIV viral load set point were assayed in participants acquiring HIV, and were correlated with the presence of prior genital infections during HIV acquisition.
Results: Thirty-five participants acquired HIV during follow-up, and 16 out of 35 (46%) had a classical sexually transmitted infection at the time of acquisition. N. gonorrhoeae coinfection was present during HIV acquisition in 6 out of 35 (17%), and was associated with an increased breadth and magnitude of systemic HIV-specific CD8 T-cell responses, using both interferon-gammaγ and MIP-1 beta as an output. No other genital infections were associated with differences in HIV-specific CD8 T-cell response, and neither N. gonorrhoeae nor other genital infections were associated with differences in HIV plasma viral load at set point.
Conclusion: Unexpectedly, genital N. gonorrhoeae infection during heterosexual HIV acquisition was associated with substantially enhanced HIV-specific CD8 T-cell responses, although not with differences in HIV viral load set point. This may have implications for the development of mucosal HIV vaccines and adjuvants.
aDepartment of Medicine, Canada
bDepartment of Medical Genetics, University of Toronto, Ontario, Canada
cDepartment of Medical Microbiology, Kenya
dDepartment of Community Health, University of Nairobi, Nairobi, Kenya
eDepartment of Microbiology, Mount Sinai Hospital, Toronto, Canada
fDepartment of Community Health Sciences and Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
gDepartment of Medicine, University Health Network, Ontario, Canada.
† Job J. Bwayo deceased.
Received 22 December, 2007
Revised 16 May, 2008
Accepted 27 May, 2008
Correspondence to Dr Rupert Kaul, Clinical Science Division, University of Toronto, Medical Sciences Building #6356, Toronto, Ontario M5S 1A8, Canada. Tel: +1 416 978 8607; fax: +1 416 978 8765; e-mail: firstname.lastname@example.org