The Clinical HIV Research Unit (CHRU) is a division of the Wits Health Consortium (Pty) Ltd. which is a wholly owned subsidiary of the University of the Witwatersrand. CHRU is located within the grounds of the Helen Joseph Hospital, a 600-bed tertiary academic hospital of Wits University located in the metropolitan centre of Johannesburg, with a second site at Sizwe Tropical Diseases Hospital on the East Rand.
Research and diagnostic studies are focused on HIV treatment in adults, HIV drug resistance, HIV prevention, multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB), Human Papillomavirus (HPV), cervical cancer screening and treatment and other viral-associated cancers. The Unit has a strong track record of Investigational New Drug (IND) level research spanning over sixteen years that has translated into significant changes in government public health policy, national guidelines and regulatory processes.
Established in 2002, WITS CHRU was the first international site to participate in the AIDS Clinical Trials Group (ACTG) Network and has completed over 50 antiretroviral therapy (ART) studies in Phase I-III research. The Unit has published over 230 papers since 2007 and more than twenty of these are related to activities of the ACTG Network and HIV Prevention Trials Network (HPTN), leading to a well above average scientific contribution score for the ACTG Network and the highest score of all the international sites (SDMC Data Management).
It is currently the highest performing and enrolling site in the ACTG Network. In addition, CHRU has maintained high marks in data quality (>98%) and recruitment and retention records demonstrate maximal use of available NIH resources, with a retention rate exceeding 99%.
The Unit has also been awarded with a National Cancer Institute AIDS Malignancy Consortium Site (NCI/AMC) and has initiated the first research protocol within Cervical Cancer treatment with radiation and chemotherapy.
The success of the site can be attributed to the outstanding access to the research populations. Helen Joseph Hospital is the premier HIV treatment facility in South Africa, supported by PEPFAR (The US President’s Emergency Plan for AIDS Relief) in a purpose renovated facility measuring over 4680m². The Themba Lethu Clinic (TLC) is one of the largest HIV and TB clinics in South Africa with over 38 000 HIV positive patients. The TB Focal Point is integrated in the HIV clinic, providing management of complicated TB cases, with an average of 200 TB patients diagnosed per month.
The leadership of CHRU reflects the diversity of skills and multi-disciplinary collaboration within Wits University and with international collaborators. Division Head Prof Ian Sanne, the newly-elected International Vice-Chair of the ACTG, also serves on numerous study protocols and guideline committees worldwide. In addition to the Principal Investigators profiled, the CHRU team consists of approximately 100 full time staff members comprising counselling, pharmacy, clinical, quality assurance, regulatory and data management teams.
Key areas of research have met the aims of the ACTG network to date, and are aligned with the network research agenda in the future; including :
The CTU Principal Investigator (Ian Sanne), Site Leader (Prudence Ive), and investigators (Cindy Firnhaber, Mohammed Rassool, Sharlaa Badal-Faesen, Noluthando Mwelas, and Karla Mellet) have all played significant leading roles in the scientific agenda of the network, participating in both administrative and scientific committees. Other key personnel, Site Coordinator (Pauline Vunandlala), Data Manager (Vuyokazi Jezile), Pharmacist (Coreen Barker), and Regulatory Manager (Marlene Naidoo) have all worked with the unit for 8-12 years. Over the last 12 years, the site has completed over 50 antiretroviral therapy studies in phase I-III research.
The attention to detail by a dedicated research team, accessing a patient population from the largest HIV and TB treatment site in southern Africa, linked to substantial investments related from PEPFAR/USAID (Right to Care) has led to this site becoming the premier performing site in the ACTG.
TLC is well equipped with systems to cater for efficient care of large volumes of patients, and which can be integrated into laboratory data and pharmacy management systems. Data can readily be exported for retrospective reviews, making the system an ideal tool for epidemiologic and economic research and monitoring. The database is used to identify the potential recruitment for more complex research studies.
The site has established an active Community Advisory Board, with members participating in the Scientific Committees and Global Community Advisory Board of the network, the latter of which has developed strategies to provide community mobilisation for TB and HIV research, outreach activities in the community, and linkage to primary health care facilities surrounding the WITS HJH site.
The site is well known for regularly being the first to open new studies of the network, based on a good working relationship with the regulatory authorities, rapid submission timeline, and highly responsive team. Procurement and importation of medicines is facilitated by the focused in-house pharmacy team under RightMed Pharmacy.
The site has emphasized the infrastructure, administration, IT infrastructure and connectivity, in-house regulatory division and data management to support a large team of over 60 research personnel.
The success of the CHRU has been due to the recruitment, retention and development of key personnel as demonstrated by increasing responsibility for clinical research, and increase in publication output and promotion under the University. Long-standing collaborations within the University environment through joint grant applications, research protocols, and publications:
International collaborations have been maintained over the last five year period. A number of the collaborators listed below have been appointed as adjunct researchers in the Wits Faculty of Health Sciences, and in a number of instances an application for promotion has been submitted to the promotions committee. The most significant collaborations are the following:
In particular the long-standing collaboration with Boston University has led to the development of an MOU detailing the interaction between the two institutions, and describing the joint effort to form the Health Economics and Epidemiology Office. This collaboration has been particularly successful, with an exchange of both faculty members and junior staff enabling the growth of the research activities and grant funding. Boston University has remained committed to the development of epidemiology and health economic skills at Wits, through the supervision of post-graduate students, assistance with the development of a fellowship programme, and has senior faculty members resident or travelling to South Africa.
CHRU has a well-established track record of funding from multiple sources to support its research activities and technical assistance. Sources of funding are substantial, recurring and significant. In particular the fourteen year relationship with the National Institute for Health, Division of AIDS has led to a number of grant mechanisms. Moreover, the provision of training grants from the Fogarty and CFAR grant mechanisms has provided funding support for prospective clinical trials.
In 2013, in a climate of challenging grant funding and sponsorship, the CHRU together with the Wits Reproductive Health and HIV Institute (WRHI) received funding from the US Government’s National Institute of Health of over $4,600,000 per annum over a seven year period. Funding will be used for the establishment of clinical trials to address the highest priorities in HIV/AIDS research, including Adult and Paediatric HIV therapeutic strategies, HIV cure, non-infectious comorbidities, and the infectious comorbidities of hepatitis and TB. Jointly our organizations form a consolidated and complementary Clinical Trials UNIT (CTU) known as the WITS HIV Research Group (WHRG) CTU.
Successful implementation of the research program has seen CHRU’s publications grow year on year since 2007 with the total to date in excess of 230 articles. Papers have been published in a variety of high impact journals such as The Lancet, the Journal of Infectious Diseases (JID), the New England Journal of Medicine, the Journal of Acquired Immune Deficiency Syndromes (JAIDS), PlosOne, Plos Medicine and the Journal of the International Union against Tuberculosis and Lung Disease (IUTLD). The citation rate for articles currently stands at more than 7,000 through Google Scholar.
Since its inception in 2004, the Themba Lethu Clinical Cohort (34,634 patients) has been the source of over 60 peer reviewed publications from researchers from CHRU alone.
The CHRU researchers presented 77 oral and poster presentations at national and international conferences including the Conference on Retroviruses and Opportunistic Infections (CROI) and the International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention in 2013.
At the 20th Annual Conference on Retroviruses and Opportunistic Infections held in Atlanta, Georgia, Alana Brenan was awarded a Young Investigators Award for “Viremia Copy-years as a Measure of Viral Load Burden and Associated Mortality Risk among Antiretroviral Therapy Patients in Johannesburg, SA” and “The Effect of 30 vs. 40mg of Stavudine vs. Tenofovir on Treatment Outcomes amongst HIV-positive Patients in Johannesburg, SA.”
In the past five years the CHRU research agenda has been focused on the development and scale-up of the treatment for HIV/AIDS. Research performed in the unit has made significant contributions to the local and international guidelines treatment response. Implementation of the national strategic plan for HIV/AIDS and TB has led to a significant expansion of access to treatment.
A shift is occurring from HIV research to a greater emphasis on M/XDR Tuberculosis, viral related cancers, and for the health economics research office non-communicable diseases such as diabetes. South Africa is such a rich resource of patient populations with significant unresolved public health emergencies, enabling ongoing growth potential in the research and implementation arena.
CHRU forms part of the Wits Faculty of Health Sciences, Department of Internal Medicine, Division of Infectious Diseases at Helen Joseph Hospital. While the unit is focused on prospective randomized control trials, integration into the balance of the Infectious Diseases division is part of the strength of the group. CHRU supports the infectious diseases service delivery offering technical assistance, expert consultation for complex cases, data systems and management, evaluation and statistics – all contributing to an expanding research and post-graduate training platform.
The research agenda in the CHRU is predominately determined by the Network funding received from the Division of AIDS/NIH. Investigator participation in setting the research agenda provides lead clinicians in the unit with the opportunity to become Principal Investigators in major global/international multicenter clinical trials.
• Optimizing treatment for HIV/AIDS and the related complications or opportunistic infections
While the first-line and second-line treatment options for HIV have been well defined, the emergence of resistance and future optimization of metabolic complications of HIV treatment provide important ongoing research questions. Studies recruiting second-line treatment failure patients are underway in the unit and are anticipated to continue for the next five years.
• Improving the diagnosis and treatment of tuberculosis
Key areas of research include:
– Optimizing the rapid diagnosis of TB including drug-resistance, point-of-care testing and monitoring treatment;
– Improved and more effective preventative therapy to treat latent tuberculosis with short-course treatment of no more than one month;
– Improvement in the first-line tuberculosis treatment to both shorten the course of treatment and improve efficacy;
– Novel treatment regimens for Multi-Drug and Extensive Drug Resistant TB.
• Improving the diagnosis, prevention and treatment of cervical cancer
Cervical cancer is the commonest cancer in women, both HIV positive and negative. The CHRU investigators under the leadership of Prof Cindy Firnhaber have successfully developed a research and implementation agenda to enhance the access to early point-of-care diagnosis and treatment.
Key areas of research include:
– Application of novel molecular diagnostics at site level to enhance the screening and early diagnosis of cervical cancer;
– Trials to determine the efficacy of a nurse led visualization and treatment programme;
– Implementation research to monitor the implementation of the HPV vaccine in both HIV positive and negative adolescents.
Established in 2002 in conjunction with the CHRU, the CAB provides the opportunity for HIV affected people, especially clinical trial participants, to understand clinical research and purposes. It is the forum to voice concerns regarding specific clinical studies, their development, implementation and outcome. It aims to increase awareness in communities and improve knowledge about HIV/AIDS and TB. It also provides assistance concerning issues related to the recruitment and retention of trial participants.
CAB works with community organizations to aid in the understanding of the role of women in society. The AIDS epidemic has taught the CAB that it is vital to address gender imbalances and power inequalities as part of a comprehensive approach. CAB is highly active in promoting awareness and dispelling myths surrounding HIV/AIDS by providing education about social and cultural factors that increase the risk of women and girls in contracting HIV.
The majority of people in South Africa regard the maintenance and practice of culture and tradition as important. Traditional leaders are highly respected and are regarded as the appropriate authorities for the enforcement of culture and tradition. As such, they have great influence and power. Harnessing this status is vital in providing education and raising awareness in certain customary practices, helping to transform harmful customary practices. The CAB is proud to have a traditional leader as a committee member.