HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers.
OBJECTIVE
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).


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 IFNgamma-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 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.


CONCLUSIONS
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.
Hirbod
Taha
T
Infectious Diseases Unit, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.
Kaul
Rupert
R
Reichard
Camilla
C
Kimani
Joshua
J
Ngugi
Elizabeth
E
Bwayo
Job J
JJ
Nagelkerke
Nico
N
Hasselrot
Klara
K
Li
Bing
B
Moses
Stephen
S
MacDonald
Kelly S
KS
Broliden
Kristina
K
D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000032:analysis; D017963:Azithromycin / Q000627:therapeutic use; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006558:Herpes Genitalis / Q000821:virology; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis*; D015994:Incidence; D007371:Interferon-gamma / Q000276:immunology; D007630:Kenya; D016015:Logistic Models; D008875:Middle Aged; D009500:Neutralization Tests; D012307:Risk Factors; D011477:Sex Work; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
D000900:Anti-Bacterial Agents; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007371:Interferon-gamma; D017963:Azithromycin