Antiviral activity of genital tract secretions after oral or topical tenofovir pre-exposure prophylaxis for HIV-1

Betsy Herold, Charlene S. Dezzutti, Barbra A. Richardson, Jeanne Marrazzo, Pedro M M Mesquita, Colleen Carpenter, Ashley Huber, Nicolette Louissaint, Mark A. Marzinke, Sharon L. Hillier, Craig W. Hendrix

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Abstract

BACKGROUND: Surrogate markers of HIV-1 pre-exposure prophylaxis and microbicide efficacy are needed. One potential surrogate is the antiviral activity in cervicovaginal lavage (CVL) after exposure to candidate products. We measured CVL antiviral activity in women using oral or vaginal tenofovir-based pre-exposure prophylaxis and correlated activity with drug and immune mediator levels. METHODS: Inhibitory activity against HIV-1 and herpes simplex virus (HSV)-2 and concentrations of interleukin (IL)-1β, IL-6, IL-8, interferon-γ, induced protein 10 (IP-10), macrophage inflammatory protein (MIP)-1α, MIP-3a, lactoferrin, secretory leukocyte protease inhibitor, and defensins were measured in CVL obtained from 60 women at baseline and after 6 weeks of a randomized sequence of oral and topical tenofovir. CVL tenofovir concentrations were measured by mass spectrometry. RESULTS: The number of women with CVL anti-HIV activity ≥90% increased significantly from 5.0% at baseline to 89.1% after daily use of 1% tenofovir gel (relative risk = 17.85, P < 0.001), but there was no increase after daily oral tenofovir. The CVL anti-HIV activity correlated with drug levels (Spearman correlation coefficient 0.64 after tenofovir gel; P < 0.001) but not with the concentrations of mucosal immune mediators. No increase in CVL anti-HSV activity was observed after either drug regimen, an observation consistent with the higher concentrations of tenofovir needed to inhibit HSV-2 infection. The CVL anti-HSV activity correlated with lactoferrin, defensins, IP-10, IL-8, and detectable levels of MIP-1α but not with drug levels. CONCLUSIONS: CVL may provide a surrogate for local but not systemic drug efficacy and a tool to better understand mucosal factors that modulate antiviral activity in genital tract secretions.

Original languageEnglish (US)
Pages (from-to)65-73
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume66
Issue number1
DOIs
StatePublished - May 1 2014

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Tenofovir
Therapeutic Irrigation
Antiviral Agents
HIV-1
Macrophage Inflammatory Proteins
Defensins
Lactoferrin
Human Herpesvirus 2
Pharmaceutical Preparations
Simplexvirus
Interleukin-8
Secretory Leukocyte Peptidase Inhibitor
Gels
HIV
Pre-Exposure Prophylaxis
Virus Diseases

Keywords

  • HIV
  • HSV-2
  • mucosal immune mediators
  • pre-exposure prophylaxis
  • tenofovir

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Antiviral activity of genital tract secretions after oral or topical tenofovir pre-exposure prophylaxis for HIV-1. / Herold, Betsy; Dezzutti, Charlene S.; Richardson, Barbra A.; Marrazzo, Jeanne; Mesquita, Pedro M M; Carpenter, Colleen; Huber, Ashley; Louissaint, Nicolette; Marzinke, Mark A.; Hillier, Sharon L.; Hendrix, Craig W.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 66, No. 1, 01.05.2014, p. 65-73.

Research output: Contribution to journalArticle

Herold, B, Dezzutti, CS, Richardson, BA, Marrazzo, J, Mesquita, PMM, Carpenter, C, Huber, A, Louissaint, N, Marzinke, MA, Hillier, SL & Hendrix, CW 2014, 'Antiviral activity of genital tract secretions after oral or topical tenofovir pre-exposure prophylaxis for HIV-1', Journal of Acquired Immune Deficiency Syndromes, vol. 66, no. 1, pp. 65-73. https://doi.org/10.1097/QAI.0000000000000110
Herold, Betsy ; Dezzutti, Charlene S. ; Richardson, Barbra A. ; Marrazzo, Jeanne ; Mesquita, Pedro M M ; Carpenter, Colleen ; Huber, Ashley ; Louissaint, Nicolette ; Marzinke, Mark A. ; Hillier, Sharon L. ; Hendrix, Craig W. / Antiviral activity of genital tract secretions after oral or topical tenofovir pre-exposure prophylaxis for HIV-1. In: Journal of Acquired Immune Deficiency Syndromes. 2014 ; Vol. 66, No. 1. pp. 65-73.
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abstract = "BACKGROUND: Surrogate markers of HIV-1 pre-exposure prophylaxis and microbicide efficacy are needed. One potential surrogate is the antiviral activity in cervicovaginal lavage (CVL) after exposure to candidate products. We measured CVL antiviral activity in women using oral or vaginal tenofovir-based pre-exposure prophylaxis and correlated activity with drug and immune mediator levels. METHODS: Inhibitory activity against HIV-1 and herpes simplex virus (HSV)-2 and concentrations of interleukin (IL)-1β, IL-6, IL-8, interferon-γ, induced protein 10 (IP-10), macrophage inflammatory protein (MIP)-1α, MIP-3a, lactoferrin, secretory leukocyte protease inhibitor, and defensins were measured in CVL obtained from 60 women at baseline and after 6 weeks of a randomized sequence of oral and topical tenofovir. CVL tenofovir concentrations were measured by mass spectrometry. RESULTS: The number of women with CVL anti-HIV activity ≥90{\%} increased significantly from 5.0{\%} at baseline to 89.1{\%} after daily use of 1{\%} tenofovir gel (relative risk = 17.85, P < 0.001), but there was no increase after daily oral tenofovir. The CVL anti-HIV activity correlated with drug levels (Spearman correlation coefficient 0.64 after tenofovir gel; P < 0.001) but not with the concentrations of mucosal immune mediators. No increase in CVL anti-HSV activity was observed after either drug regimen, an observation consistent with the higher concentrations of tenofovir needed to inhibit HSV-2 infection. The CVL anti-HSV activity correlated with lactoferrin, defensins, IP-10, IL-8, and detectable levels of MIP-1α but not with drug levels. CONCLUSIONS: CVL may provide a surrogate for local but not systemic drug efficacy and a tool to better understand mucosal factors that modulate antiviral activity in genital tract secretions.",
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AU - Herold, Betsy

AU - Dezzutti, Charlene S.

AU - Richardson, Barbra A.

AU - Marrazzo, Jeanne

AU - Mesquita, Pedro M M

AU - Carpenter, Colleen

AU - Huber, Ashley

AU - Louissaint, Nicolette

AU - Marzinke, Mark A.

AU - Hillier, Sharon L.

AU - Hendrix, Craig W.

PY - 2014/5/1

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N2 - BACKGROUND: Surrogate markers of HIV-1 pre-exposure prophylaxis and microbicide efficacy are needed. One potential surrogate is the antiviral activity in cervicovaginal lavage (CVL) after exposure to candidate products. We measured CVL antiviral activity in women using oral or vaginal tenofovir-based pre-exposure prophylaxis and correlated activity with drug and immune mediator levels. METHODS: Inhibitory activity against HIV-1 and herpes simplex virus (HSV)-2 and concentrations of interleukin (IL)-1β, IL-6, IL-8, interferon-γ, induced protein 10 (IP-10), macrophage inflammatory protein (MIP)-1α, MIP-3a, lactoferrin, secretory leukocyte protease inhibitor, and defensins were measured in CVL obtained from 60 women at baseline and after 6 weeks of a randomized sequence of oral and topical tenofovir. CVL tenofovir concentrations were measured by mass spectrometry. RESULTS: The number of women with CVL anti-HIV activity ≥90% increased significantly from 5.0% at baseline to 89.1% after daily use of 1% tenofovir gel (relative risk = 17.85, P < 0.001), but there was no increase after daily oral tenofovir. The CVL anti-HIV activity correlated with drug levels (Spearman correlation coefficient 0.64 after tenofovir gel; P < 0.001) but not with the concentrations of mucosal immune mediators. No increase in CVL anti-HSV activity was observed after either drug regimen, an observation consistent with the higher concentrations of tenofovir needed to inhibit HSV-2 infection. The CVL anti-HSV activity correlated with lactoferrin, defensins, IP-10, IL-8, and detectable levels of MIP-1α but not with drug levels. CONCLUSIONS: CVL may provide a surrogate for local but not systemic drug efficacy and a tool to better understand mucosal factors that modulate antiviral activity in genital tract secretions.

AB - BACKGROUND: Surrogate markers of HIV-1 pre-exposure prophylaxis and microbicide efficacy are needed. One potential surrogate is the antiviral activity in cervicovaginal lavage (CVL) after exposure to candidate products. We measured CVL antiviral activity in women using oral or vaginal tenofovir-based pre-exposure prophylaxis and correlated activity with drug and immune mediator levels. METHODS: Inhibitory activity against HIV-1 and herpes simplex virus (HSV)-2 and concentrations of interleukin (IL)-1β, IL-6, IL-8, interferon-γ, induced protein 10 (IP-10), macrophage inflammatory protein (MIP)-1α, MIP-3a, lactoferrin, secretory leukocyte protease inhibitor, and defensins were measured in CVL obtained from 60 women at baseline and after 6 weeks of a randomized sequence of oral and topical tenofovir. CVL tenofovir concentrations were measured by mass spectrometry. RESULTS: The number of women with CVL anti-HIV activity ≥90% increased significantly from 5.0% at baseline to 89.1% after daily use of 1% tenofovir gel (relative risk = 17.85, P < 0.001), but there was no increase after daily oral tenofovir. The CVL anti-HIV activity correlated with drug levels (Spearman correlation coefficient 0.64 after tenofovir gel; P < 0.001) but not with the concentrations of mucosal immune mediators. No increase in CVL anti-HSV activity was observed after either drug regimen, an observation consistent with the higher concentrations of tenofovir needed to inhibit HSV-2 infection. The CVL anti-HSV activity correlated with lactoferrin, defensins, IP-10, IL-8, and detectable levels of MIP-1α but not with drug levels. CONCLUSIONS: CVL may provide a surrogate for local but not systemic drug efficacy and a tool to better understand mucosal factors that modulate antiviral activity in genital tract secretions.

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