Semi-Annual Performance Report (SAPR) for OPTIMIZE Consortium

The consortium participated in the Technical Steering Committee (TSC) and Programme Advisory Committee (PAC) meetings, with the TSC providing a platform for progress updates, challenges, and achievements. The PAC meeting in November 2017 discussed progress on ART optimization activities funded through USAID and Unitaid, and provided recommendations, including the need for a third arm to the DE2FT study. Wits RHI also coordinated structured engagements, including partner-exclusive conference calls, face-to-face meetings, and progress updates via the newsletter. The newsletter facilitated sharing of updates on ART optimization work from other projects, such as NAMSAL, Aurum, and CHAI. The OPTIMIZE joint TSC and PAC meetings were held in Washington DC in November 2017 and in Geneva in September 2018. The consortium's Workstream 1 focused on clinical studies around DTG, TAF, and low-dose EFV. ADVANCE completed recruitment of 1053 participants in May 2018, and the DSMB approved the suspension of recruitment of adolescents. The study shifted focus to retention activities to maintain statistical power. WRHI052, the low-dose DRV study, completed its last participant's last visit in June 2018, with a 100% retention rate of participants who completed on-study visits up to Week 48. The plasma PK substudy will provide information on DRV concentrations and virological suppression, as well as fasting glucose, triglyceride, and cholesterol concentrations. The DaRiFi study investigates DRV with rifampicin (RIF) in TB participants. The study timelines were moved forward due to a temporary hold imposed in January 2018, and subsequent to the approval of secured funding, resources were reinstated, and the study is back on track with enrollment of cohort 1 started in May 2018. Workstream 2 focused on developing new ARVs, including DRV/r SDNs. Three lead candidates for DRV/r SDNs (ratios 8:1, 6:1, and 4:1) were recommended for progression at the TSC/PAC and have been taken into accelerated stability testing at the University of Liverpool. A contract manufacturing organization, Juniper Pharma Services, has been contracted to complete feasibility stability studies on materials made by the University of Liverpool, as well as manufacture of all three DRV/r formulations, and subsequent stability in accelerated conditions. Workstream 3 focused on implementation support for new optimal ARVs, including dolutegravir (DTG) 50mg. ICAP supported the Government of Kenya to refine plans and implement the use of dolutegravir-containing regimens. ICAP also supported Kenya to improve its pharmacovigilance system through the development and installation of an Enhanced Data System (EDS). ICAP provided support to Mozambique through sharing findings from the needs assessment completed in Y2, and provision of technical assistance to transition planning in-country.