TY - JOUR
T1 - Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women
AU - Bártolo, Inês
AU - Diniz, Ana Rita
AU - Borrego, Pedro
AU - Ferreira, João Pedro
AU - Bronze, Maria Rosário
AU - Barroso, Helena
AU - Pinto, Rui
AU - Cardoso, Carlos
AU - Pinto, João F.
AU - Diaz, Rafael Ceña
AU - Broncano, Pilar Garcia
AU - Muñoz-Fernández, Maria Angel
AU - Taveiraz, Nuno
N1 - Publisher Copyright:
© 2018 Bártolo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/4
Y1 - 2018/4
N2 - Microbicides are an important strategy for preventing the sexual transmission of HIV but, so far, the most advanced tenofovir-based microbicides have had modest efficacy. This has been related to adherence problems and high prevalence of tenofovir-resistant HIV-1 strains. P3 is a new peptide with potent activity against HIV that may be a good microbicide candidate. In this work P3 was formulated in a gel of hydroxyethyl cellulose and its activity, stability and safety profile in Balb/c mice were evaluated. HIV infection was fully blocked by a 1.5% gel containing P3 at the IC90 (366.4 nM) concentration. The antiviral activity did not change at 4°C during 4 months and at 25, 37 and 65°C for 1 week. P3 was stable and fully functional at acidic pH up to 24h, under different concentrations of hydrogen peroxide and in the presence of genital fluids up to 48h. P3 had no antibacterial activity and did not affect sperm motility and vitality. Finally, P3 didn't cause significant alterations in the vaginal epithelium of Balb/c mice at 0.06 (456.8 μM) and 0.2 mg/day (1522.7 μM) doses. These findings indicate that P3 is an excellent candidate for further development as a microbicide gel for the prevention of HIV transmission in women.
AB - Microbicides are an important strategy for preventing the sexual transmission of HIV but, so far, the most advanced tenofovir-based microbicides have had modest efficacy. This has been related to adherence problems and high prevalence of tenofovir-resistant HIV-1 strains. P3 is a new peptide with potent activity against HIV that may be a good microbicide candidate. In this work P3 was formulated in a gel of hydroxyethyl cellulose and its activity, stability and safety profile in Balb/c mice were evaluated. HIV infection was fully blocked by a 1.5% gel containing P3 at the IC90 (366.4 nM) concentration. The antiviral activity did not change at 4°C during 4 months and at 25, 37 and 65°C for 1 week. P3 was stable and fully functional at acidic pH up to 24h, under different concentrations of hydrogen peroxide and in the presence of genital fluids up to 48h. P3 had no antibacterial activity and did not affect sperm motility and vitality. Finally, P3 didn't cause significant alterations in the vaginal epithelium of Balb/c mice at 0.06 (456.8 μM) and 0.2 mg/day (1522.7 μM) doses. These findings indicate that P3 is an excellent candidate for further development as a microbicide gel for the prevention of HIV transmission in women.
UR - http://www.scopus.com/inward/record.url?scp=85045888895&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0195744
DO - 10.1371/journal.pone.0195744
M3 - Article
C2 - 29668740
AN - SCOPUS:85045888895
SN - 1932-6203
VL - 13
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e0195744
ER -
