P43.08Use of a Mathematical Model to Predict DissolutionProfiles of Dapivirine Vaginal Rings

Christopher Gilmour, Stephen Ampofo, Brid Devlin

International Partnership for Microbicides, Product Develop-ment, Silver Spring, MD, United States

Background: The dapivirine vaginal ring is a sustained releaseformulation containing dapivirine, a potent antiviral currently inclinical evaluation for HIV prevention. Each ring contains 25 mgof dapivirine in a platinum-cured silicone matrix. In vitro dis-solution testing quantifies the amount of dapivirine releasedfrom the ring over the 28-day use period, but is labor intensive,time consuming and expensive. This paper describes develop-ment of a mathematical model to predict average cumulativedrug release of a batch.Methods: Empirical approaches and mechanistic considerationswere used to modify the Higuchi equation so as to assess theamount of dapivirine released per unit area of the vaginal ring.The model utilizes details of ring geometry, ring assay and asingle attribute of the silicone elastomer:Q = (2A)1/2(Cp*Dp)1/2 · {polynomial (order 2) of t} WhereQ = amount of active ingredient released per unit areaA = concentration of active ingredient in the matrixCp = solubility of active ingredient in the matrixDp = diffusion coefficient of the active ingredient in the matrixt = time, set at 281/2

The model was assessed for applicability to batch averages.Average 14-day results were also used to estimate (Cp*Dp)1/2 forindividual batches in order to improve the model.Results: The model resulted in errors typically within therange + /- 4% for the predicted 28-day average cumulative re-lease versus actual average cumulative release. The accuracy ofthe model was improved further by using the 14-day results toestimate (Cp*Dp)1/2 for individual batches.Conclusions: Data from mathematical models indicate that ringattributes or results from earlier time points can predict 28-daydissolution in terms of average cumulative amount of drug releasedper batch or from an individual ring. These predictions provide areliable and efficient measure for product quality control.

P43.09Trends of Advocacy Journalism; a Case of the HIV/AIDS Story in the Ugandan Press

Kakaire A. Kirunda1,2, Angelo Kaggwa- Katumba3

1Islamic University in Uganda, Mass Communication, Kam-pala, Uganda, 2Makerere University College of Health Sci-ences, School of Public Health, Health Policy Planning andManagement, Kampala, Uganda, 3AVAC: Global Advocacy forHIV Prevention, New York, NY, United States

Background: The genre of advocacy journalism is one whichjournalists can employ to advance HIV prevention effortsranging from policy to practice. Advocacy journalism deliber-ately but transparently adopts a non-objective viewpoint, usuallyfor some social purpose. Usually, in advocacy journalism,practitioners have an opinion about the story they are writing.We therefore sought to establish the extent to which the strate-gically placed front page HIV/AIDS stories in Uganda’s leadingdaily newspapers are a product of advocacy journalism.

Methods: A retrospective desk review of the Daily Monitor andNew Vision newspapers covering the period January 2013 throughDecember 2013 was used. The two newspapers were purposivelyselected and HIV/AIDS articles obtained from the cover pageswere coded against a set of variables. Two key informants werealso interviewed. Data was entered into SPSS (Statistical Packagefor the Social Sciences) software for analysis while qualitative datafrom the articles was analysed using thematic content analysis.Results: The sample for both newspapers yielded a combined2154 articles on the front pages. However, findings indicate thatout of these, only 28 articles (1.3%) were about HIV/AIDS withthe Daily Monitor having 16 while New Vision carried only 12.Overall, most of the articles had an element of advocacy jour-nalism. In the New Vision, 9 (75%) front page articles wereslanted towards advocacy, while in the Daily Monitor this wasexhibited in 14 (88%) articles. In both newspapers, the jour-nalists systematically employed a positive tone, the choice offacts supported the cause the headlines were fronting andsourcing for the articles was favourable. All these attributes aresynonymous with advocacy journalism.Conclusions: With majority of HIV/AIDS articles that make itto the front pages being products of advocacy journalism, pre-vention advocates need seize the opportunity. Ways of workingwith the authors of these articles should be devised to tap intoadvocacy opportunities.

P43.10Tenofovir Diphosphate Concentrations in HumanVaginal Stroma after Different Dosage Regimenswith a Vaginal Gel: A Modeling Approach

Yajing Gao1, Andrew Yuan1, David F. Katz1,2

1Duke University, Durham, NC, United States, 2Duke Uni-versity Medical Center, Obstetrics and Gynecology, Durham,NC, United States

Background: Different vaginal dosing (BAT24, daily) of the 1%Tenofovir (TFV) gel gave differing pharmacokinetics and pro-phylactic efficacy. The kinetics of stromal Tenofovir diphosphate(TFV-DP) production/loss are governed by many factors, e.g.:mass transport kinetics of TFV to stroma; concentration distribu-tion of stromal host cells; TFV binding and phosphorylation ratesto/in host cells; and TFV-DP clearance rate in host cells. Experi-mental PK studies give guidance on creation and persistence ofstromal TFV-DP levels, but optimization of dosing to achieve suchlevels is limited. Modeling this process complements experimentalstudies, providing insights on how the multiple factors governTFV-DP levels and suggesting optimal dosing strategies.Methods: A mechanistic, mass transport-based model wascreated of TFV delivery to human vaginal mucosa by aspreading gel, and coupled TFV-DP production in stromal hostcells. Parameters in the model were obtained from in vitromeasurements of gel rheology and TFV transport properties,human vaginal morphometric and histological data, and resultsof human PK studies for the 1% TFV gel. Single and multiple gelapplication regimens were studied, including coitus.Results: Results show, for example, that application of twodoses 4 hours apart (as found in BAT24) gives 40% highermaximum stromal TFV-DP concentration than daily dosing.This elevated TFV-DP concentration is sustained for 4 days vsdaily dosing (due primarily to the long half life of TFV-DP).Conclusions: Modeling provides additional insights about inter-active effects of the multiple factors that govern optimal dosing by

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