Antiretroviral pre-exposure prophylaxis does not enhance immune responses to HIV in exposed but uninfected persons

Partners PrEP Study Team

Research output: Contribution to journalArticle

Abstract

Background. Antiretroviral preexposure prophylaxis (PrEP), using daily oral combination tenofovir disoproxil fumarate plus emtricitabine, is an effective human immunodeficiency virus (HIV) prevention strategy for populations at high risk of HIV acquisition. Although the primary mode of action for the protective effect of PrEP is probably direct antiviral activity, nonhuman primate studies suggest that PrEP may also allow for development of HIV-specific immune responses, hypothesized to result from aborted HIV infections providing a source of immunologic priming. We sought to evaluate whether PrEP affects the development of HIV-specific immune response in humans. Methods and Results. Within a PrEP clinical trial among high-risk heterosexual African men and women, we detected HIV-specific CD4+ and CD8+ peripheral blood T-cell responses in 10%-20% of 247 subjects evaluated. The response rate and magnitude of T-cell responses did not vary significantly between those assigned PrEP versus placebo, and no significant difference between those assigned PrEP and placebo was observed in measures of innate immune function. Conclusions. We found no evidence to support the hypothesis that PrEP alters either the frequency or magnitude of HIV-specific immune responses in HIV-1-exposed seronegative individuals. These results suggest that PrEP is unlikely to serve as an immunologic prime to aid protection by a putative HIV vaccine.

Original languageEnglish (US)
Pages (from-to)1943-1952
Number of pages10
JournalJournal of Infectious Diseases
Volume211
Issue number12
DOIs
StatePublished - Jun 15 2015

Fingerprint

HIV
Tenofovir
Placebos
T-Lymphocytes
Pre-Exposure Prophylaxis
Heterosexuality
Virus Diseases
Primates
Antiviral Agents
HIV-1
Blood Cells
Vaccines
Clinical Trials

Keywords

  • cellular immunity
  • HIV-1
  • prevention of sexual transmission
  • T-lymphocyte

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Antiretroviral pre-exposure prophylaxis does not enhance immune responses to HIV in exposed but uninfected persons. / Partners PrEP Study Team.

In: Journal of Infectious Diseases, Vol. 211, No. 12, 15.06.2015, p. 1943-1952.

Research output: Contribution to journalArticle

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abstract = "Background. Antiretroviral preexposure prophylaxis (PrEP), using daily oral combination tenofovir disoproxil fumarate plus emtricitabine, is an effective human immunodeficiency virus (HIV) prevention strategy for populations at high risk of HIV acquisition. Although the primary mode of action for the protective effect of PrEP is probably direct antiviral activity, nonhuman primate studies suggest that PrEP may also allow for development of HIV-specific immune responses, hypothesized to result from aborted HIV infections providing a source of immunologic priming. We sought to evaluate whether PrEP affects the development of HIV-specific immune response in humans. Methods and Results. Within a PrEP clinical trial among high-risk heterosexual African men and women, we detected HIV-specific CD4+ and CD8+ peripheral blood T-cell responses in 10{\%}-20{\%} of 247 subjects evaluated. The response rate and magnitude of T-cell responses did not vary significantly between those assigned PrEP versus placebo, and no significant difference between those assigned PrEP and placebo was observed in measures of innate immune function. Conclusions. We found no evidence to support the hypothesis that PrEP alters either the frequency or magnitude of HIV-specific immune responses in HIV-1-exposed seronegative individuals. These results suggest that PrEP is unlikely to serve as an immunologic prime to aid protection by a putative HIV vaccine.",
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AU - Pattacini, Laura

AU - Murnane, Pamela M.

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AU - Thomas, Katherine K.

AU - Bukusi, Elizabeth

AU - Katabira, Elly

AU - Mugo, Nelly

AU - Donnell, Deborah

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AU - Celum, Connie

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AU - Lund, Jennifer M.

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AU - Tumwesigye, Elioda

AU - Ndase, Patrick

AU - Ronald, Allan

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AB - Background. Antiretroviral preexposure prophylaxis (PrEP), using daily oral combination tenofovir disoproxil fumarate plus emtricitabine, is an effective human immunodeficiency virus (HIV) prevention strategy for populations at high risk of HIV acquisition. Although the primary mode of action for the protective effect of PrEP is probably direct antiviral activity, nonhuman primate studies suggest that PrEP may also allow for development of HIV-specific immune responses, hypothesized to result from aborted HIV infections providing a source of immunologic priming. We sought to evaluate whether PrEP affects the development of HIV-specific immune response in humans. Methods and Results. Within a PrEP clinical trial among high-risk heterosexual African men and women, we detected HIV-specific CD4+ and CD8+ peripheral blood T-cell responses in 10%-20% of 247 subjects evaluated. The response rate and magnitude of T-cell responses did not vary significantly between those assigned PrEP versus placebo, and no significant difference between those assigned PrEP and placebo was observed in measures of innate immune function. Conclusions. We found no evidence to support the hypothesis that PrEP alters either the frequency or magnitude of HIV-specific immune responses in HIV-1-exposed seronegative individuals. These results suggest that PrEP is unlikely to serve as an immunologic prime to aid protection by a putative HIV vaccine.

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KW - prevention of sexual transmission

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