The University of North Carolina (UNC) Global HIV Clinical Trials Unit (CTU) has a well established track record of high-quality, innovative clinical research, strong scientific leadership (both in and outside the NIH HIV/AIDS Networks), and access to critically important infected and at-risk populations in the Southeastern US and in Southern Africa. Drawn from a diverse team of clinical innvestigators spanning two continents, our CTU will be led by three experienced principal investigators (Joseph Eron MD, Jeffrey Stringer MD and Mina Hosseinipour MD) and will support all 5 NIH HIV Clinical Trials Networks: Adult Therapeutic Strategies, Strategies to Address HIV and HIV-associated Infections in Pediatric and Maternal Populations, Integrated HIV Prevention Strategies, Microbicide Strategies, and Vaccine Strategies to Prevent HIV Infection. The 5 Clinical Research Sites (CRS) will include Chapel Hill CRS led by David Wohl MD (Adult Therapeutic Strategies, Integrated Prevention, Microbicide and Vaccine), Raleigh CRS led by Kristine Patterson MD (Adult Therapeutic Strategies, Integrated Prevention, Vaccine), Greensboro CRS led by Cornelius Van Dam MD PhD (Adult Therapeutic Strategy and Integrated Prevention), Malawi CRS led by Francis Martinson MD PhD (all 5 Networks) and Zambia CRS led by Benjamin Chi MD (all 5 Networks). Supporting this leadership will be Network Science Teams, comprising global experts and site collaborators who will work to execute the network scientific agendas. The CTU has also assembled a diverse group of senior scientists and public health officials to serve on our Scientific and Strategic Advisory Group. The CTU administration incorporates a highly organized structure that will be responsive to our experienced research teams across the 5 sites and will provide ongoing evaluation to ensure optimal performance and efficiency. The CTU will be supported by state-of-the-art communications and has assembled outstanding laboratory, pharmacy, quality assurance, data management and regulatory support. With its robust administrative framework, the UNC Global HIV CTU will be uniquely positioned to provide scientific leadership and clinical trials infrastructure to advance the field of agenda of he NlAID networks.
The NIH has established collaborative HIV/AIDS Clinical Trials Networks to advance the science of HIV prevention, care, and treatment. The UNC Global Clinical Trials Unit is eager to participate in this research, by reaching populations most affecte by the epidemic in North America and Africa and by contributing key scientific leadership to drive the research agenda. RESUME AND SUMMARY OF DISCUSSION FOR COMPONENT 1 RESEARCH OVERVIEW: The RESUME AND SUMMARY OF DISCUSSION section summarizes the final opinion of the committee after the discussion and is the basis for the assigned Overall Impact/Priority score for Component 1. This discussion was taken into consideration by the review committee in assigning an Overall Impact/Priority score for the CTU application. The key scientific priorities of the CTU are the: 1) Design of HIV-1 reservoir reduction and cure strategies; 2) Impact of ongoing inflammation and activation on non-infectious co-morbidities; 3) Diagnosis and treatment of active and latent TB and TB prevention in resource limited setting; 4) Treatment of HCV and HCV/HIV co-infections including use of direct acting agents; 5) Treatment strategies for HIV-infected women and children and children at-risk; 6) Strategies addressing HIV and women's health, including family planning and gynecologic cancers; 7) Integrated prevention strategies with a focus on the use of antiretrovirals in prevention including in HIV positive individuals and as PrEP and microbicides for those at-risk; 8) Availability and enrollment of crucial high risk populations in Africa and southern US for vaccine studies; and 9) Evaluation of novel strategies to improve service effectiveness, through rigorously designed, controlled implementation studies Several strengths are identified in Component 1. The three experienced leaders have complementary scientific expertise. The institutional resources, the organized and centralized administrative structure for all components, and the clear lines of authority and leadership for each clinical area are excellent. The proposed areas of clinical trials research are highly significant. There is access to vulnerable HIV populations and they propose innovative strategies to access marginalized populations. There is exceptional focus on implementation science, pediatric and adolescent issues and the prevention of mother-to-child transmission strategies in resource-constrained settings. Other important research areas are treatment as prevention in injection drug users (IDU) and combination interventions targeting HIV latency. The creation of Network Liaisons from each CRS region, organized by the network priority areas, is innovative. The CTU leadership has the ability to use the Network Science Teams (NSTs) for rapid reconfiguration to meet the needs of a continually emerging scientific agenda. A mouse model of HIV latency and the detection and quantification of anti-retroviral levels in genital issues are examples of innovative technologies the CTU has access to at UNC. The use of social media for recruitment and behavioral interventions with mobile devices and the Electronic Medical Record systems in Zambia are strengths. The support and integration of the three domestic and two African sites and the environments at all the sites also are exceptional. Several weaknesses are identified in Component 1. There was significant discussion among the reviewers about the absence of local scientific and operational leadership at both African sites and the lack of a plan to accelerate mentorship of the very experienced local researchers. It is unclear to the review committee why African PIs do not have prominent senior leadership roles in the CTU organizational structure when the CTU has a history of mentoring the African sites for several years. The review committee recommends that steps are taken to remedy this situation and to mobilize efforts to engage African PIs in leadership positions. The review committee also is concerned that the potential hazards of technological innovations such as breaches of confidentiality and privacy concerns are not always well considered in resource-limited settings. Details also are lacking on how prompt communication with international CRSs and NST members at those CRSs will be facilitated. Although the engagement of Community Advisory Boards (CABs) with the CTU and CRS leadership is addressed, it is unclear how the CAB will provide feedback to the community and how the CTU will involve the Malawi government to accommodate public health policy changes. Although the CTU proposes to support all five networks, some of the areas are untested. It also is unclear how the CTU will contribute to modifications to future clinical protocols. There are unclear lack of lines of authorty between the study implementation staff and the CRS coordinators at UNC that could present areas of conflict. Although there is sufficient expertise to address biomedical research issues, the review committee is disappointed that expertise is lacking in socio-behavioral areas and that issues with adherence are not adequately discussed. Based on the scientific and technical merits and the identified strengths, Component 1 received an Overall Impact score of 15.
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