HIV-neutralizing immunoglobulin a and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers
Hirbod, T.; Kaul, R.; Reichard, C.; Kimani, J.; Ngugi, E.; Bwayo, J.J.; Nagelkerke, N.; Hasselrot, K.; Li, B.; Moses, S.; MacDonald, K.S.; Broliden, K.; Keli, F.; Kamunyo, G.; Wanguru, R.; Mwakisha, R.; Waithira, G.; Nganga, D.; Nyambogo, C.; Ombette, J.; Njeri, J.; Onyango, I.; Malonza, I.; Mwangi, F.; Fonck, K.; Temmerman, M.; Ronald, A.R.; Luscher, M.
Aids 22(6): 727-735
2008
ISSN/ISBN: 1473-5571 PMID: 18356602 DOI: 10.1097/qad.0b013e3282f56b64Document Number: 199823
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). 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 IFNgamma-modified enzyme-linked immunospot and proliferative responses. 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 IFNgamma 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. 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.