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P43.08 Use of a Mathematical Model to Predict Dissolution Profiles of Dapivirine Vaginal Rings Christopher Gilmour, Stephen Ampofo, Brid Devlin International Partnership for Microbicides, Product Development, Silver Spring, MD, United States Background: The dapivirine vaginal ring is a sustained release formulation containing dapivirine, a potent antiviral currently in clinical evaluation for HIV prevention. Each ring contains 25 mg of dapivirine in a platinum-cured silicone matrix. In vitro dissolution testing quantifies the amount of dapivirine released from the ring over the 28-day use period, but is labor intensive, time consuming and expensive. This paper describes development of a mathematical model to predict average cumulative drug release of a batch. Methods: Empirical approaches and mechanistic considerations were used to modify the Higuchi equation so as to assess the amount of dapivirine released per unit area of the vaginal ring. The model utilizes details of ring geometry, ring assay and a single attribute of the silicone elastomer: Q = (2A)1/2(Cp*Dp)1/2 · {polynomial (order 2) of t} Where Q = amount of active ingredient released per unit area A = concentration of active ingredient in the matrix Cp = solubility of active ingredient in the matrix Dp = diffusion coefficient of the active ingredient in the matrix t = 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 for individual batches in order to improve the model. Results: The model resulted in errors typically within the range + /- 4% for the predicted 28-day average cumulative release versus actual average cumulative release. The accuracy of the model was improved further by using the 14-day results to estimate (Cp*Dp)1/2 for individual batches. Conclusions: Data from mathematical models indicate that ring attributes or results from earlier time points can predict 28-day dissolution in terms of average cumulative amount of drug released per batch or from an individual ring. These predictions provide a reliable and efficient measure for product quality control.

P43.09 Trends of Advocacy Journalism; a Case of the HIV/ AIDS Story in the Ugandan Press Kakaire A. Kirunda1,2, Angelo Kaggwa- Katumba3 1

Islamic University in Uganda, Mass Communication, Kampala, Uganda, 2Makerere University College of Health Sciences, School of Public Health, Health Policy Planning and Management, Kampala, Uganda, 3AVAC: Global Advocacy for HIV Prevention, New York, NY, United States Background: The genre of advocacy journalism is one which journalists can employ to advance HIV prevention efforts ranging from policy to practice. Advocacy journalism deliberately but transparently adopts a non-objective viewpoint, usually for 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 strategically placed front page HIV/AIDS stories in Uganda’s leading daily newspapers are a product of advocacy journalism.

Methods: A retrospective desk review of the Daily Monitor and New Vision newspapers covering the period January 2013 through December 2013 was used. The two newspapers were purposively selected and HIV/AIDS articles obtained from the cover pages were coded against a set of variables. Two key informants were also interviewed. Data was entered into SPSS (Statistical Package for the Social Sciences) software for analysis while qualitative data from the articles was analysed using thematic content analysis. Results: The sample for both newspapers yielded a combined 2154 articles on the front pages. However, findings indicate that out of these, only 28 articles (1.3%) were about HIV/AIDS with the Daily Monitor having 16 while New Vision carried only 12. Overall, most of the articles had an element of advocacy journalism. In the New Vision, 9 (75%) front page articles were slanted towards advocacy, while in the Daily Monitor this was exhibited in 14 (88%) articles. In both newspapers, the journalists systematically employed a positive tone, the choice of facts supported the cause the headlines were fronting and sourcing for the articles was favourable. All these attributes are synonymous with advocacy journalism. Conclusions: With majority of HIV/AIDS articles that make it to the front pages being products of advocacy journalism, prevention advocates need seize the opportunity. Ways of working with the authors of these articles should be devised to tap into advocacy opportunities.

P43.10 Tenofovir Diphosphate Concentrations in Human Vaginal Stroma after Different Dosage Regimens with a Vaginal Gel: A Modeling Approach Yajing Gao1, Andrew Yuan1, David F. Katz1,2 1

Duke University, Durham, NC, United States, 2Duke University 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 prophylactic 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 distribution of stromal host cells; TFV binding and phosphorylation rates to/in host cells; and TFV-DP clearance rate in host cells. Experimental PK studies give guidance on creation and persistence of stromal TFV-DP levels, but optimization of dosing to achieve such levels is limited. Modeling this process complements experimental studies, providing insights on how the multiple factors govern TFV-DP levels and suggesting optimal dosing strategies. Methods: A mechanistic, mass transport-based model was created of TFV delivery to human vaginal mucosa by a spreading gel, and coupled TFV-DP production in stromal host cells. Parameters in the model were obtained from in vitro measurements of gel rheology and TFV transport properties, human vaginal morphometric and histological data, and results of human PK studies for the 1% TFV gel. Single and multiple gel application regimens were studied, including coitus. Results: Results show, for example, that application of two doses 4 hours apart (as found in BAT24) gives 40% higher maximum stromal TFV-DP concentration than daily dosing. This elevated TFV-DP concentration is sustained for 4 days vs daily dosing (due primarily to the long half life of TFV-DP). Conclusions: Modeling provides additional insights about interactive effects of the multiple factors that govern optimal dosing by

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the TFV gel. Results here illustrate pharmacokinetic benefits of multiple dosing within a few hours vs sustained daily dosing. This approach can be used to help optimize dosage regimen, accounting for factors such as gel volume and drug loading.

P43.11 Persistent HIV-related Stigma in Rural Uganda during a Period of Increasing HIV Incidence Brian T. Chan1,2, Sheri D. Weiser3, Yap Boum4, Mark J. Siedner1, A R. Mocello3, Jessica E. Haberer1, Peter W. Hunt3, Jeffrey N. Martin3, Kenneth H. Mayer5, David R. Bangsberg1, Alexander C. Tsai1 1

Massachusetts General Hospital, Boston, MA, United States, Brigham and Women’s Hospital, Boston, MA, United States, 3 UCSF, San Francisco, CA, United States, 4Epicentre, Mbarara, Uganda, 5Fenway Health, Boston, MA, United States 2

Background: Uganda is the only country in sub-Saharan Africa with increasing HIV incidence during the period 2002–2013. Because HIV-related stigma is associated with reduced uptake of HIV testing, increased risk-taking behavior, decreased adherence to anti-retroviral therapy (ART), and reduced HIV status disclosure, it is critical to understand how changes in HIV incidence have correlated with HIV-related stigma during this period. Methods: We analyzed data from two sources: 1) the Uganda AIDS Rural Treatment Outcomes (UARTO) study during 2007–2012 and 2) the Uganda Demographic and Health Surveys (DHS) from 2006 and 2011 to estimate trends in internalized stigma among people living with HIV (PLHIV) at ART initiation and trends in stigmatizing attitudes and anticipated stigma among the general population. We fit regression models adjusted for socio-demographic characteristics, with year of cohort entry/ DHS as the primary explanatory variable.

Results: Among people initiating ART in the UARTO study, we found a statistically significant positive association between year of ART initiation and internalized stigma score (adjusted b = 0.17; 95% CI, 0.05 to 0.29), suggesting an 11% relative increase in the mean score in each year of recruitment after the first year. From 1.4 (out of 4) at baseline, the mean stigma score increased to a peak of 2.2 in 2011. Among the general population comparing 2011 with 2006 DHS data, we found a significantly higher odds of reporting anticipated stigma (adjusted OR = 1.12; 95% CI, 1.08 to 1.17), despite a decreased odds of reporting stigmatizing attitudes (adjusted OR = 0.90; 95% CI, 0.87 to 0.93). Conclusions: Mean internalized stigma at ART initiation increased over time among PLHIV in a rural Ugandan cohort in the setting of worsening anticipated stigma among the general population. Further study is needed to better understand the reasons for increasing HIV-related stigma and its impact on HIV prevention efforts in Uganda.

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AIDS Law Project, Nairobi, Kenya, 2Networking HIV/AIDS Community of South Africa, Cape Town, South Africa, 3Positive Action for Treatment Access, Lagos, Nigeria, 4Partners in Prevention PrEP Thika Study Site, Thika, Kenya, 5Centre for Sexual Health and HIV/AIDS Research, Harare, Zimbabwe, 6 Health Development Initiative, Kigali, Rwanda, 7China HIV/ AIDS Information Network, Beijing, China Background: Through the AVAC fellowship, selected advocates from Kenya, Rwanda, Nigeria, Zimbabwe, South Africa and China worked with the aim of empowering the population with knowledge and to advocate for treatment as prevention in their countries that targeted the community and policy makers. Methods: Advocacy took place in the span of a year where three advocates from Kenya, Rwanda and China worked to increase the demand and access of PrEP in their countries. They targeted key populations consisting of sex workers, gay men, male sex workers and sero-discordant couples, policy makers and civil society. In the communities they created awareness for the program among the recipients and other non-governmental organizations and advocated for government to adopt the program for the country. In Zimbabwe, South Africa, Nigeria and Kenya, four advocates increased demand and awareness of treatment as prevention and good participatory practice in clinical trials. The Kenya, Zimbabwe and Nigeria advocates increased demand by advocating for early initiation of people living with HIV, initiation of sero-discordant couples regardless of CD4 count in Kenya, increase of post exposure prophylaxis access to sex workers in Zimbabwe and in South Africa increase of effective engagement of communities in trials through the development of treatment guidelines and change in policy in Kenya, Zimbabwe and Nigeria and engaging researchers and communities is South Africa. Results: There is need for scale up of PrEP programs in countries with key populations as consultations in the targeted countries showed a demand for the services. There is need to create more community engagement in programs to also increase access among populations. Early initiation and lifelong treatment among mothers is timely and the demand among communities is also high, strides should be taken to fully roll out these programs. Conclusions: Civil society groups in other countries should also seek to create demand among communities on new prevention technologies.

P43.13 Ending HIV among Men Who Have Sex with Men (MSM) in Kenya: Community Recommendations on Scaling up HIV Prevention and Treatment Jeffrey W. Wambaya1, Leonard Mutisya2, Gaudensia Mutua3, Jack Ndegwa4, George O. Owino5 1

Ishtar MSM, Nairobi, Kenya, 2UHAI EASHRI, Nairobi, Kenya, 3KAVI, Nairobi, Kenya, 4KANCO, Nairobi, Kenya, 5 IAVI, Nairobi, Kenya

P43.12 Using Advocacy, Guideline and Policy Change to Increase Treatment Demand in Various Parts of Africa and Asia Maureen Akumu Milanga1, Ntando Yola2, Oladayo Taiwo Oyelakin3, Peter Michira4, Rumbidzai Mapfumo5, Josephine Kamarebe6, Cai Lingping7

Background: MSM in Kenya contribute 15% of new HIV infections yearly even when only 1% of men report same-sex sexual activity. There has been no conclusive participatory strategy that has engaged MSM nationally in developing HIV prevention responses for and by MSM. Kenyan MSM community organisations purposed to design and advocate for a com-

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