HIV This Week

Hirbod T, Kaul R, Reichard C, Kimani J, Ngugi E, Bwayo JJ, Nagelkerke N, Hasselrot K, Li B, Moses S; Kibera HIV Study Group, MacDonald KS, Broliden K. Collaborators: 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 AR, Luscher M. HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers. AIDS. 2008;22(6):727-35.

HIV-neutralizing immunoglobulin A (IgA) and HIV-specific cellular immunity have been described in highly exposed, persistently seronegative individuals, but well controlled studies have not been performed. Hirbod and colleagues 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. A randomized trial of monthly antibiotic prophylaxis to prevent sexually transmitted disease/HIV infection was performed from 1998 to 2002 in HIV-uninfected Kenyan female sex workers. After the completion of trial, female sex workers 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 IFN-gamma-modified enzyme-linked immunospot and proliferative responses. The study cohort comprised 113 female sex workers: 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 IFN-gamma 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.

Editors´note: Much is to be learned from the careful study of the immune responses of high exposed, persistently seronegative individuals, whether they are sex workers or seronegative people in long-term discordant partnerships. In this study, two independent factors were prospectively associated with reduced sexual acquisition: HIV-neutralizing immunoglobulin A (IgA) and HIV-specific proliferation in cervicovaginal lavage specimens. Herpes simplex-2 infection interfered with this partial protection by reducing HIV-neutralizing IgA in the genital tract. How to induce such protective humoral immune responses in the genital tract, whether they are associated with specific host genetics, and how they might combine with strong cellular responses are questions waiting to be answered.