SPL7013 Gel (VivaGel) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans

Clare F Price, David Tyssen, Secondo Sonza, Ashley Davie, Sonya Evans, Gareth R Lewis, Shirley Xia, Tim Denis Spelman, Peter Hodsman, Thomas R Moench, Andrew J Humberstone, Jeremy RA Paull, Gilda Tachedjian

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Abstract

SPL7013 Gel (VivaGel((R))) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3 SPL7013 Gel in healthy women. Participants received 5 single doses of product with >/=5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p90 of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46 of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70 inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov under identifier: NCT00740584.
Original languageEnglish
Article numbere24095
Number of pages12
JournalPLoS ONE
Volume6
Issue number9
DOIs
Publication statusPublished - 2011

Cite this

Price, Clare F ; Tyssen, David ; Sonza, Secondo ; Davie, Ashley ; Evans, Sonya ; Lewis, Gareth R ; Xia, Shirley ; Spelman, Tim Denis ; Hodsman, Peter ; Moench, Thomas R ; Humberstone, Andrew J ; Paull, Jeremy RA ; Tachedjian, Gilda. / SPL7013 Gel (VivaGel) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans. In: PLoS ONE. 2011 ; Vol. 6, No. 9.
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title = "SPL7013 Gel (VivaGel) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans",
abstract = "SPL7013 Gel (VivaGel((R))) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3 SPL7013 Gel in healthy women. Participants received 5 single doses of product with >/=5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p90 of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46 of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70 inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov under identifier: NCT00740584.",
author = "Price, {Clare F} and David Tyssen and Secondo Sonza and Ashley Davie and Sonya Evans and Lewis, {Gareth R} and Shirley Xia and Spelman, {Tim Denis} and Peter Hodsman and Moench, {Thomas R} and Humberstone, {Andrew J} and Paull, {Jeremy RA} and Gilda Tachedjian",
year = "2011",
doi = "10.1371/journal.pone.0024095",
language = "English",
volume = "6",
journal = "PLoS ONE",
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Price, CF, Tyssen, D, Sonza, S, Davie, A, Evans, S, Lewis, GR, Xia, S, Spelman, TD, Hodsman, P, Moench, TR, Humberstone, AJ, Paull, JRA & Tachedjian, G 2011, 'SPL7013 Gel (VivaGel) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans', PLoS ONE, vol. 6, no. 9, e24095. https://doi.org/10.1371/journal.pone.0024095

SPL7013 Gel (VivaGel) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans. / Price, Clare F; Tyssen, David; Sonza, Secondo; Davie, Ashley; Evans, Sonya; Lewis, Gareth R; Xia, Shirley; Spelman, Tim Denis; Hodsman, Peter; Moench, Thomas R; Humberstone, Andrew J; Paull, Jeremy RA; Tachedjian, Gilda.

In: PLoS ONE, Vol. 6, No. 9, e24095, 2011.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - SPL7013 Gel (VivaGel) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans

AU - Price, Clare F

AU - Tyssen, David

AU - Sonza, Secondo

AU - Davie, Ashley

AU - Evans, Sonya

AU - Lewis, Gareth R

AU - Xia, Shirley

AU - Spelman, Tim Denis

AU - Hodsman, Peter

AU - Moench, Thomas R

AU - Humberstone, Andrew J

AU - Paull, Jeremy RA

AU - Tachedjian, Gilda

PY - 2011

Y1 - 2011

N2 - SPL7013 Gel (VivaGel((R))) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3 SPL7013 Gel in healthy women. Participants received 5 single doses of product with >/=5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p90 of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46 of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70 inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov under identifier: NCT00740584.

AB - SPL7013 Gel (VivaGel((R))) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3 SPL7013 Gel in healthy women. Participants received 5 single doses of product with >/=5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p90 of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46 of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70 inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov under identifier: NCT00740584.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174146/pdf/pone.0024095.pdf

U2 - 10.1371/journal.pone.0024095

DO - 10.1371/journal.pone.0024095

M3 - Article

VL - 6

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 9

M1 - e24095

ER -