lubricity and coating sensations at initial penetration or duringthe first coital strokes were problematic, even causing a fewcouples to stop sex.Conclusions: The addition of vaginal film to the formulationparameter space for USPEs of vaginal products offers importantconsiderations for developers. Given previous USPE analyses,initial lubrication may impact use adherence and thus is cur-rently being explored in new film development.

P15.13Using Molecular Dynamics Techniques to Investigatethe Influence of Glycans on the HIV-1 gp120 EnvelopeProtein Trimer

Clint Mercuur, Natasha Wood, Simon Travers

University of the Western Cape, South African NationalBioinformatics Institute, Cape Town, South Africa

Background: The gp120 glycoprotein present on the surface ofthe HIV virion is crucial for the recognition and binding toreceptors on the host cell surface, as well as facilitation of thefusion of the viral envelope to the host cell membrane. Thesurface of gp120 is covered with N-linked glycans that can in-fluence HIV-1 infectivity as well as affect the recognition of thevirus by the host immune system, acting as a ‘‘glycan shield’’from antibody recognition.Methods: Previous research has shown that the N-linked gly-cans bound to the surface of a gp120 monomer have a significantimpact on the underlying dynamics of the protein.Here, we have expanded on this work by undertaking moleculardynamic modeling to explore the effect of N-linked glycans onthe dynamics of the full gp120 trimer.Results: Our results illustrate the significance of the silent andactive faces of the gp120 monomers, as well as showing thetrimer-specific behavior of the glycans and glycan-protein in-teractions.Conclusions: Collectively our results provide a better under-standing of the role that the glycan composition and distributionplay during infection of a new cell.

P15.14Development of a Temperature-recording VaginalRing for Monitoring User Adherence

Peter Boyd1, Clare McCoy1, Diarmaid Murphy1, Manjula Lusti-Narasimhan2, Berglind Helgadottir3, Karl Malcolm1

1Queen’s University Belfast, School of Pharmacy, Belfast,United Kingdom, 2World Health Organization (WHO), Geneva,Switzerland, 3Star-Oddi Ltd., Gardabaer, Iceland

Background: Vaginal ring devices are being actively developedfor controlled delivery of HIV microbicides and as multi-purpose prevention technology (MPT) products combininghormonal contraception with prevention of HIV and other sexu-ally transmitted diseases. Presently, there is no reliable method formonitoring user adherence in HIV vaginal ring trials; previousacceptability studies have included some type of participant self-reporting mechanism, which have often been unreliable. Moreobjective, quantitative and accurate methods for assessing ad-herence are needed.Methods: A silicone elastomer vaginal ring containing an en-capsulated miniature temperature recording device has been

developed that can capture and store real-time temperature dataduring the period of designated use. Devices were tested in bothsimulated vaginal environments and following vaginal place-ment in cynomolgus macaques. Various use protocols and datasampling rates were tested to simulate typical patient usagescenarios.Results: The temperature logging devices accurately recordedvaginal temperature in macaques, clearly showing the regulardiurnal temperature cycle. When environmental temperature andvaginal temperature was significantly different, the device wasable to accurately pinpoint the insertion and removal times. Basedon the data collected it was possible to infer removal periods asshort as 5 min when the external environmental temperature was25�C. Accuracy increased with data sampling rate.Conclusions: This work provides proof-of-concept for moni-toring adherence using a vaginal ring device containing an en-capsulated temperature logger. The addition of one or moreactive agents into the ring body is not anticipated to affect thetemperature monitoring function. A clinical study to compareself-reported user adherence data with that obtained by the de-vice would be highly informative.

P15.15Potential of RNA Aptamers in the Prevention of HIV-1Subtype C Infections

Grace Mothepane London1, Makobetsa Khati1,2, BonganiMayosi2

1CSIR, Biosciences, Pretoria, South Africa, 2University of CapeTown, Medicine, Cape Town, South Africa

Background: Compounds that have been used to prevent humanimmunodeficiency virus type-I (HIV-1) infections include syn-thetic chemicals, plant extras and monoclonal antibodies. Al-though most of these compounds have potent antiviral activity,they often fail to progress to later stages of clinical trials due tohigh toxicity and lack of specificity. Therefore, as an alternativeto circumvent the above mentioned limitations we used apta-mers, which are small nucleic acid ligands that recognize theirtarget with high specificity and have no toxicity in clinical ap-plications.Methods: In this study, we evaluated efficacy of four gp120-aptamers against Env pseudovirus panel derived from HIV-1subtype C, using virus inhibition assay in TZM-bl cells, as wellas toxicity. Binding specificity of one potent aptamer(CSIR1.1) to gp120 was determined by Enzyme-Linked-Im-munosorbent Assay. Subsequently, a virus inhibition assay wasperformed to test whether CSIR1.1 can inhibit HIV-1 pseu-dotyped with vesicular stomatitis virus envelope glycoprotein(HIV-VSVG.Results: All four aptamers inhibited infectivity of 81-84 % ofthe tested viruses with mean inhibition concentration (IC50) of6.4-9 nM. The specificity results showed that CSIR1.1 onlybound to gp120 and did not bind other tested proteins (HIV-1gp41, mycobacterium tuberculosis virulent protein (CFP10),human interferon gamma (IFN-c) and BSA). CSIR1.1 also failedto inhibit HIV-1 pseudotyped with VSV-G protein and showedno toxicity in vitro, even at concentration (500 nM), which was5 · higher than one used for virus inhibition assays.Conclusions: Aptamers showed significant efficacy againstHIV-1 subtype C isolates and specificity to gp120 withoutcausing cytoxicity effects. These properties make aptamers at-tractive candidates for prevention of HIV-1.

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