The Safety, Tolerability, and Preliminary Efficacy of a Gemcitabine-releasing Intravesical System (TAR-200) in American Urological Association-defined Intermediate-risk Non-muscle-invasive Bladder Cancer Patients: A Phase 1b Study.

Background and objective: Patients with intermediate-risk non-muscle-invasive bladder cancer (IR NMIBC) have a high risk of recurrence and need effective therapies to reduce the risk of disease recurrence or progression. This phase 1b study (NCT02720367) assessed the safety and tolerability of TAR-200, an intravesical drug delivery system, in participants with IR NMIBC. Methods: Participants with recurrent IR NMIBC were eligible. Participants received either two 7-d or two 21-d TAR-200 dosing cycles over a 4-6-wk period in a marker lesion/ablation design. TAR-200 was placed in the window between the cystoscopy showing recurrent papillary disease and the subsequent complete transurethral resection of the bladder tumour. The primary endpoint was TAR-200 safety. The secondary endpoints included TAR-200 tolerability, pharmacokinetics, and preliminary efficacy. Key findings and limitations: Twelve participants received TAR-200 treatment. No TAR-200-related serious or grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred. Nine participants had grade ≤ 2 TAR-200-related TEAEs, with urgency, dysuria, and haematuria being most common. Two participants refused a second dosing cycle due to urinary urgency and frequency. Insertion and removal of TAR-200 was successful in all cases. Plasma gemcitabine concentrations remained below the lower limit of detection. Five participants (42%) had complete response (CR): four had pathological CR and one had CR based on visual assessment. Conclusions and clinical implications: TAR-200 appears to be safe and well tolerated, with encouraging preliminary efficacy in participants with IR NMIBC. This study lays the groundwork for the multiple phase 2 and 3 global studies that are currently on-going for TAR-200. Patient summary: In this study, researchers evaluated the safety of the novel drug delivery system TAR-200 in participants with intermediate-risk non-muscle-invasive bladder cancer. They concluded that TAR-200 was safe and well tolerated with promising antitumour activity.

Promotion of couples' voluntary HIV counseling and testing: a comparison of influence networks in Rwanda and Zambia.

BACKGROUND: Many African adults do not know that partners in steady or cohabiting relationships can have different HIV test results. Despite WHO recommendations for couples' voluntary counseling and testing (CVCT), fewer than 10 % of couples have been jointly tested and counseled. We examine the roles and interactions of influential network leaders (INLs) and influential network agents (INAs) in promoting CVCT in Kigali, Rwanda and Lusaka, Zambia. METHODS: INLs were identified in the faith-based, non-governmental, private, and health sectors. Each INL recruited and mentored several INAs who promoted CVCT. INLs and INAs were interviewed about demographic characteristics, promotional efforts, and working relationships. We also surveyed CVCT clients about sources of CVCT information. RESULTS: In Zambia, 53 INAs and 31 INLs were surveyed. In Rwanda, 33 INAs and 27 INLs were surveyed. Most (75 %-90 %) INAs believed that INL support was necessary for their promotional work. Zambian INLs reported being more engaged with their INAs than Rwandan INLs, with 58 % of Zambian INLs reporting that they gave a lot of support to their INAs versus 39 % in Rwanda. INAs in both Rwanda and Zambia reported promoting CVCT via group forums (77 %-97 %) and speaking to a community leader about CVCT (79 %-88 %) in the past month. More Rwandan INAs and INLs reported previous joint or individual HIV testing compared with their Zambian counterparts, of which more than half had not been tested. In Zambia and Rwanda, 1271 and 3895 CVCT clients were surveyed, respectively. Hearing about CVCT from INAs during one-on-one promotions was the most frequent source of information reported by clients in Zambia (71 %). In contrast, Rwandan couples who tested were more likely to have heard about CVCT from a previously tested couple (59 %). CONCLUSIONS: CVCT has long been endorsed for HIV prevention but few couples have been reached. Influential social networks can successfully promote evidence-based HIV prevention in Africa. Support from more senior INLs and group presentations leveraged INAs' one-on-one promotions. The INL/INA model was effective in promoting couples to seek joint HIV testing and counseling and may have broader application to other sub-Saharan African countries to sustainably increase CVCT uptake.

Knowledge and perceptions of couples' voluntary counseling and testing in urban Rwanda and Zambia: a cross-sectional household survey.

BACKGROUND: Most incident HIV infections in sub-Saharan Africa occur between cohabiting, discordant, heterosexual couples. Though couples' voluntary HIV counseling and testing (CVCT) is an effective, well-studied intervention in Africa, <1% of couples have been jointly tested. METHODS: We conducted cross-sectional household surveys in Kigali, Rwanda (n = 600) and Lusaka, Zambia (n = 603) to ascertain knowledge, perceptions, and barriers to use of CVCT. RESULTS: Compared to Lusaka, Kigali respondents were significantly more aware of HIV testing sites (79% vs. 56%); had greater knowledge of HIV serodiscordance between couples (83% vs. 43%); believed CVCT is good (96% vs. 72%); and were willing to test jointly (91% vs. 47%). Stigma, fear of partner reaction, and distance/cost/logistics were CVCT barriers. CONCLUSIONS: Though most respondents had positive attitudes toward CVCT, the majority were unaware that serodiscordance between cohabiting couples is possible. Future messages should target gaps in knowledge about serodiscordance, provide logistical information about CVCT services, and aim to reduce stigma and fear.