Objectives: HIV-neutralizing immunoglobulin A (IgA) and HIV-specific cellular immunity have been described in highly exposed, persistently seronegative (HEPS) individuals, but well controlled studies have not been performed. We performed a prospective, nested case–control study to examine the association of genital IgA and systemic cellular immune responses with subsequent HIV acquisition in high-risk Kenyan female sex workers (FSWs).
Design and methods: A randomized trial of monthly antibiotic prophylaxis to prevent sexually transmitted disease/HIV infection was performed from 1998 to 2002 in HIV-uninfected Kenyan FSWs. After the completion of trial, FSWs who had acquired HIV (cases) were matched 1: 4 with persistently uninfected controls based on study arm, duration of HIV-seronegative follow-up, and time of cohort enrolment. Blinded investigators assayed the ability at enrolment of genital IgA to neutralize primary HIV isolates as well as systemic HIV-specific cellular IFNγ-modified enzyme-linked immunospot and proliferative responses.
Results: The study cohort comprised 113 FSWs: 24 cases who acquired HIV and 89 matched controls. Genital HIV-neutralizing IgA was associated with reduced HIV acquisition (P = 0.003), as was HIV-specific proliferation (P = 0.002), and these associations were additive. HIV-specific IFNγ production did not differ between case and control groups. In multivariable analysis, HIV-neutralizing IgA and HIV-specific proliferation each remained independently associated with lack of HIV acquisition. Genital herpes (HSV2) was associated with increased HIV risk and with reduced detection of HIV-neutralizing IgA.
Conclusion: Genital HIV-neutralizing IgA and systemic HIV-specific proliferative responses, assayed by blinded investigators, were prospectively associated with HIV nonacquisition. The induction of these immune responses may be an important goal for HIV vaccines.
From the aInfectious Diseases Unit, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden
bDepartment of Medical Microbiology, Kenya
cDepartment of Community Health, University of Nairobi, Nairobi, Kenya
dDepartment of Medicine, University of Toronto, Canada
eDepartment of Medicine, University Health Network, Canada
fDepartment of Microbiology, Mount Sinai Hospital, Toronto, Canada
gDepartment of Community Medicine, United Arab Emirates University, AlAin, UAE
hDepartment of Medical Microbiology, Canada
iDepartment of Community Health Sciences and Medicine, University of Manitoba, Winnipeg, Canada.
* These authors contributed equally to the work.
† Members listed in acknowledgements section.
‡These authors contributed equally to the work.
Received 5 September, 2007
Revised 23 November, 2007
Accepted 10 December, 2007
Correspondence to Dr Kelly S. MacDonald, Mount Sinai Hospital, Room 1484, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5. E-mail: email@example.com