The BC Centre for Excellence in HIV/AIDS: An agency of change

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Compiled By: BC-CfE and Shawn Lawrence

The BC Centre for Excellence in HIV/AIDS (BC-CfE) was first established by the BC Minister of Health in 1992. At that time, there was much anxiety and little clarity on what was the best approach to manage the HIV epidemic.

The idea proposed was to establish a single agency with a specific mandate to improve and prolong life for people infected with HIV in the province. In that context, BC-CfE was created with a mandate to procure and distribute HIV treatments guided by specially developed provincial guidelines, as well as to prospectively monitor the efficacy, safety, impact and cost effectiveness of the program, and to feed this knowledge back into the development of management guidelines and novel programs. Given the above mandate, the BC-CfE has over the last 17 years provided unique insight into the epidemic, with an emphasis on therapeutic issues.

The first steps taken by the BC-CfE involved bringing in a broad interdisciplinary team that embraced comprehensive research, monitoring and an evaluation agenda encompassing epidemiological, clinical, laboratory, behavioral and operational sciences.

Specific effort was put forth to connect all of these areas and to provide as much feedback as possible to its program’s development activities. Additionally, the centre appointed a pioneer in the field of HIV/AIDS clinical work and research, Dr. Julio Montaner, as its director of clinical research.

Now the appointed director, Montaner feels that surveillance and forecasting are an essential part of the BC-CfE’s activities which help it to gain a better understanding of where the epidemic is going and what to do about it. Likewise, taking research from the bench to bedside is also stated goal of the centre.

“All along we’ve placed a special emphasis on enhancing our ability to translate new knowledge, whether it was generated within the BC-CfE or elsewhere, immediately to practice,” states Montaner, who on top of his role as director of BC-CfE, is also the president of the International AIDS Society, and co-director of the Canadian HIV Trials Network.

“Over the years the BC-CfE has developed a unique ability to transition from the bench, to bedside, to policy, and as we monitor the responses to the epidemic we continue to feed that loop to further our mandate,” he states.

As a result, the BC-CfE was the first to recognize a new epidemic emerging in the Downtown Eastside of Vancouver, affecting injection drug users in the mid 1990s, which allowed rapid mobilization of resources to address this formidable challenge.

Another important aspect of the BC-CfE’s work is the evaluation of safety and efficacy of its programs. The BC-CfE has also contributed significantly to the development of novel strategies to manage HIV-resistant virus in the community.

“This is of critical importance, particularly in a very rapidly evolving field of medicine, where state-of-the-art technology is rapidly changing.

Furthermore, this is especially important as minorities and other groups – potentially highly vulnerable groups – are typically underrepresented in clinical trials. Yet these groups are prominently affected by HIV/AIDS and consequently within our programs when they are deployed in the community. Early on, we pioneered a new management strategy including multiple drug rescue therapy at a time when patients with multiple drug-resistant virus were generally felt to be untreatable. Using multiple drug combinations in the setting of multiple drug-resistant virus we were able to render over 50 per cent of patients undetectable. In other words, their disease was put in remission, which at the time was thought to be impossible.”

Dr. Montaner is quite proud of the centre’s milestones under his leadership, with the influence it has had in the fight against the spread of HIV/AIDS, and also in the positive initiatives it has helped to launch spurring forward public health innovation and policy implementation.

Specifically, BC-CfE has played a key role developing a number of new treatments for HIV infection and its complications.

Perhaps the most significant among them was the pioneering work in the development of non nucleoside reverse transcriptase (NNRTI)-based highly active antiretroviral therapy (HAART), which has now become the global standard of HIV care.

Dr. Montaner was the lead investigator of the seminal clinical trial that demonstrated that NNRTI – based HAART could render HIV plasma levels undetectable and lead to full remission of the disease. Montaner unveiled this groundbreaking research at the International AIDS Conference held in Vancouver in 1996.

“In 1996, as the organizers and co-chairs of the International AIDS Society-sponsored AIDS conference in Vancouver, we had the opportunity to rapidly and effectively disseminate the benefits of HAART, so that this was rapidly adopted in the developed world with similar gains.”

In fact, it is interesting to note that long before these findings were presented and the actual peer reviewed papers were published, BC-CfE had implemented this approach more than 18 months before with outstanding success.

“By the time the papers were out, AIDS mortality had already declined by over 75 per cent among HIV-infected individuals engaged in care in BC,” Montaner says.
This was not the only such novel discovery related to antiretrovirals made at the centre.

“Over the years, we have also characterized several new emerging toxicities to novel antiretrovirals, (ARV’s) including most recently d4T-related mitochondrial toxicity. Largely as a result of these findings, we abandoned the use of this agent and in December the World Health Organization (WHO) recommended that d4T be abandoned in the developing world,” he adds.

BC-CfE has also developed comprehensive strategies to tailor antiretroviral therapy to the specific needs of the patient, including viral resistance testing, human genetic testing and pharmacological testing, which have greatly contributed to enhance the safety, efficacy and tolerability of current regimens. The BC-CfE has also pioneered harm reduction research, including the scientific evaluation of the first North American supervised injecting facility.

Moreover, Dr Montaner has long been a proponent of using HIV drugs as a means to not only treat the disease but also as a means to prevent its spread. Over the last several years, Dr. Montaner has focused his attention to the potential role of HAART on the control of HIV transmission.

“We have provided evidence that the viral load suppression achieved by HAART has a substantial impact on the transmission of HIV. Specifically, in August 2006, we published a viewpoint article in The Lancet that outlined the expansion of HAART coverage to all those in medical need as a key strategy to dramatically reduce HIV transmission to those at risk. We further proposed that HAART expansion – in addition to preventing AIDS morbidity and mortality – would become cost-averting as it would virtually eliminate vertical transmission of HIV and dramatically reduce HIV transmission by all routes (Lima et al, JID, 2008).”

Dr. Monataner adds that there is evidence to support the powerful and sustained ability of HAART to suppress viral replication and is responsible for the decreased risk of HIV transmission among treated HIV-positive individuals can be readily found in vertical transmission studies where the use of HAART has led to the near complete prevention of transmission of HIV from the infected mother to the newborn. Further, among sero-discordant couples (one infected and one uninfected partner), transmission is a direct function of the level of viremia in the infected member of the couple. This level is effectively decreased to very low levels with HAART, dramatically reducing risk of transmission.

“More recently, we published (Wood et al, British Medical Journal, 2009), the first study demonstrating the role of HAART in the prevention of transmission in injection drug users in the Downtown Eastside of Vancouver. At the population level, the BC-CfE has documented that expanded HAART uptake was associated with approximately a 50% reduction in HIV incidence in BC between 1996 and 1999 when HAART was first introduced in BC (Anema, Eur JID, 2009, in press),” he says.

While the BC-CfE’s proposal of using “Treatment as Prevention” was initially regarded as controversial, the notion has gained the support of the international community, including the WHO and the Joint United Nations Programme on HIV/AIDS (UNAIDS). In fact, as recently as January 2009, the AIDS program at WHO published a paper in The Lancet, which independently validated BC-CfE’s proposed approach (Granich et al, The Lancet, 2009).

In February 2009, an international summit in Vancouver co-convened by the International AIDS Society, the World Bank and the Global Fund, with support from the Public Health Agency of Canada and with participation of WHO, UNAIDS, PEPFAR, the Clinton Initiative, Médecins Sans Frontières, the National Institutes of Health, and international research-based pharmaceutical industries, among other key international stakeholders, charted the course for further expansion of HAART in the developing world centered on the proposed “Treatment as Prevention” initiative.

“The expansion of HAART, currently proposed in BC, aims to increase coverage from the current 5,000 on treatment to approximately 7,500 clinically eligible HIV-positive individuals. The proposal also includes plans to measure the expansion of HAART impact on HIV incidence, as well as AIDS morbidity and mortality over six years. Our mathematical modeling suggests that this will generate approximately a 30% decline in HIV incidence. We have entitled this initiative Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS).”

In general, the centre has also been a conduit through which the province has attracted a number of complementary initiatives. These include the CIHR funded Canadian HIV Trials network, based at St Paul’s Hospital and UBC, and several HIV/AIDS clinical trials. The UBC-Division of AIDS in the Department of Medicine housed at the centre is the first and only one of its kind in Canada. Likewise, the BC-CfE has attracted substantial brainpower to BC, including researchers like Dr. Richard Harrigan, director of the BC-CfE’s Research Laboratory, and Dr. Thomas Kerr, co-director of the Urban Health Research Initiative of the BC-CfE.

Earlier this year, BC-CfE recruited Dr. Art Poon, a young IT scientist from California, along with Drs. Zabrina Brumme and Mark Brockman, two basic scientists from Harvard. More recently, the BC-CfE garnered further international recognition with Dr. Montaner being named as the president of the International AIDS society for 2008-2010 term. The appointment was seen in many circles as a sign of the strengthened position of both BC and Canada at the table of the largest HIV organization in the world.

Furthermore, earlier this year, the Centre secured for the second consecutive time the CIHR National Knowledge Translation award. Both are clear indications that the activities and pioneering efforts of the centre are being recognized both nationally and globally.