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

Taha Hirbod; Rupert Kaul; Camilla Reichard; Joshua Kimani; Elizabeth Ngugi; Job J. Bwayo; Nico Nagelkerke; Klara Hasselrot; Bing Li; Stephen Moses; Kelly S. MacDonald; Kristina Broliden; Florence Keli; Grace Kamunyo; Ruth Wanguru; Rachel Mwakisha; Grace Waithira; Daniel Nganga; Cornelius Nyambogo; John Ombette; Jane Njeri; Isaiah Onyango; Isaac Malonza; Francis Mwangi; Karolien Fonck; Marleen Temmerman; Allan R. Ronald; Mark Luscher

doi:10.1097/QAD.0b013e3282f56b64

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

Taha Hirbod, Rupert Kaul, Camilla Reichard, Joshua Kimani, Elizabeth Ngugi, Job J. Bwayo, Nico Nagelkerke, Klara Hasselrot, Bing Li, Stephen Moses, Kelly S. MacDonald, Kristina Broliden, Florence Keli, Grace Kamunyo, Ruth Wanguru, Rachel Mwakisha, Grace Waithira, Daniel Nganga, Cornelius Nyambogo, John OmbetteJane Njeri, Isaiah Onyango, Isaac Malonza, Francis Mwangi, Karolien Fonck, Marleen Temmerman, Allan R. Ronald, Mark Luscher

Centre of Excellence in Women and Child Health, East Africa

Research output: Contribution to journal › Article › peer-review

89 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	727-735
Number of pages	9
Journal	AIDS
Volume	22
Issue number	6
DOIs	https://doi.org/10.1097/QAD.0b013e3282f56b64
Publication status	Published - Mar 2008

Keywords

Cellular proliferation
Exposed uninfected
HIV
Immunoglobulin A
Neutralization

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/QAD.0b013e3282f56b64

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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., ... Luscher, M. (2008). HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers. AIDS, 22(6), 727-735. https://doi.org/10.1097/QAD.0b013e3282f56b64

@article{8a93f73dad4c4a5c8ddb5e50ef9afbde,

title = "HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers",

abstract = "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.",

keywords = "Cellular proliferation, Exposed uninfected, HIV, Immunoglobulin A, Neutralization",

author = "Taha Hirbod and Rupert Kaul and Camilla Reichard and Joshua Kimani and Elizabeth Ngugi and Bwayo, {Job J.} and Nico Nagelkerke and Klara Hasselrot and Bing Li and Stephen Moses and MacDonald, {Kelly S.} and Kristina Broliden and Florence Keli and Grace Kamunyo and Ruth Wanguru and Rachel Mwakisha and Grace Waithira and Daniel Nganga and Cornelius Nyambogo and John Ombette and Jane Njeri and Isaiah Onyango and Isaac Malonza and Francis Mwangi and Karolien Fonck and Marleen Temmerman and Ronald, {Allan R.} and Mark Luscher",

year = "2008",

month = mar,

doi = "10.1097/QAD.0b013e3282f56b64",

language = "English",

volume = "22",

pages = "727--735",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "6",

}

Hirbod, T, Kaul, R, Reichard, C, Kimani, J, Ngugi, E, Bwayo, JJ, Nagelkerke, N, Hasselrot, K, Li, B, Moses, S, MacDonald, KS, 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, AR & Luscher, M 2008, 'HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers', AIDS, vol. 22, no. 6, pp. 727-735. https://doi.org/10.1097/QAD.0b013e3282f56b64

TY - JOUR

T1 - HIV-neutralizing immunoglobulin A and HIV-specific proliferation are independently associated with reduced HIV acquisition in Kenyan sex workers

AU - Hirbod, Taha

AU - Kaul, Rupert

AU - Reichard, Camilla

AU - Kimani, Joshua

AU - Ngugi, Elizabeth

AU - Bwayo, Job J.

AU - Nagelkerke, Nico

AU - Hasselrot, Klara

AU - Li, Bing

AU - Moses, Stephen

AU - MacDonald, Kelly S.

AU - Broliden, Kristina

AU - Keli, Florence

AU - Kamunyo, Grace

AU - Wanguru, Ruth

AU - Mwakisha, Rachel

AU - Waithira, Grace

AU - Nganga, Daniel

AU - Nyambogo, Cornelius

AU - Ombette, John

AU - Njeri, Jane

AU - Onyango, Isaiah

AU - Malonza, Isaac

AU - Mwangi, Francis

AU - Fonck, Karolien

AU - Temmerman, Marleen

AU - Ronald, Allan R.

AU - Luscher, Mark

PY - 2008/3

Y1 - 2008/3

N2 - 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.

AB - 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.

KW - Cellular proliferation

KW - Exposed uninfected

KW - HIV

KW - Immunoglobulin A

KW - Neutralization

UR - http://www.scopus.com/inward/record.url?scp=41349105330&partnerID=8YFLogxK

U2 - 10.1097/QAD.0b013e3282f56b64

DO - 10.1097/QAD.0b013e3282f56b64

M3 - Article

C2 - 18356602

AN - SCOPUS:41349105330

SN - 0269-9370

VL - 22

SP - 727

EP - 735

JO - AIDS

JF - AIDS

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

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