Canadian HIV/AIDS research: Key achievements 2000-2009

A Report prepared for the Canadian Institutes of Health Research HIV/AIDS Research Initiative by Mark Bisby and Michelle Campbell

March 2010

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Table of Contents

• Executive Summary
• Introduction
  • History of Government of Canada HIV/AIDS research support
    • Federal Initiative to Address HIV/AIDS in Canada
    • Canadian HIV Vaccine Initiative (CHVI)
    • CIHR management of the Federal Initiatives
  • Objectives of this analysis
• Funding for HIV/AIDS research
  • CIHR funding mechanisms for HIV/AIDS
  • Other funding for HIV/AIDS research in Canada
  • Complementarity of CIHR funding mechanisms
  • Commercialization and industry-partnered funding
  • Who is funded by CIHR?
• Capacity-building
  • Investment in training and salary awards
  • Number of Investigators Supported
  • Where are the added investigators coming from?
    • Biomedical/Clinical stream
    • Health services/Population health stream
  • Where are the trainees going?
    • Biomedical/Clinical stream
    • Health services/Population health stream
• Research productivity
  • Productivity and research funding
  • Canadian research productivity
    • Health services/Population health stream
    • Community-based research
    • CBR sub-stream on Aboriginal health
  • Productivity of elite investigators
  • International comparisons of productivity
  • Trends in focus of Canadian research
    • Areas of Canadian research specialization
• Quality of Canadian research publications
  • Subfields of HIV/AIDS research
    • Aboriginal health stream
  • Most-cited publications
  • Most-productive authors
• Collaborations
  • International collaboration
  • Collaborating with knowledge users
• Public awareness
• Conclusion: Research contributions to the Federal Initiative to Address HIV/AIDS in Canada
  • Goal 1: Prevent the acquisition and transmission of new infections
  • Goal 2: Slow the progression of the disease and improve quality of life
  • Goal 3: Reduce the social and economic impact of HIV/AIDS
  • Goal 4: Contribute to the global effort to reduce the spread and impact of HIV
    
    
• Boxes 1 – 8: Canadian research rising to the challenge
  
  
  • 1. AIDS was a death sentence
  • 2. Getting the right treatment to the right person
  • 3. The HIV virus is never entirely gone
  • 4. Engaging communities to find answers that really work
  • 5. Half of those in BC who died of AIDS never got treated
  • 6. Why are some people immune to HIV?
  • 7. How does a small country add value to global work
  • 8. Preventing the spread of HIV/AIDS
    
    
• Appendix: List of Key Informants

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Executive Summary

Introduction

CIHR manages the research component of the Government of Canada's two major HIV/AIDS initiatives: the Federal Initiative to Address HIV/AIDS in Canada (FI) and the Canadian HIV Vaccine Initiative. These targeted funds are managed through the CIHR HIV/AIDS Research Initiative (HIV Initiative). Since 2001, CIHR has invested a total of $134 million through the HIV Initiative, and an additional $150 million of its core funds, in HIV/AIDS research. The goal of this report is to identify the most significant health and research impacts of this Canadian investment in HIV/AIDS research.

Our report describes a number of Canada's most critical research achievements, as identified by key informants and complemented by funding and publication data. While research successes like these cannot be attributed to any single funder, Canada's best HIV/AIDS researchers have all received important support through CIHR.

Changes in funding

CIHR's regular and HIV-Initiative funding seem to be complementary, supporting, for the most part, different groups of researchers with different aims. The community-based research stream, in particular, supports many who would not be funded through regular CIHR programs. The majority of both regular CIHR and HIV Initiative funding has gone to operating grants, while the latter has also made a significant investment in the CIHR Canadian HIV Trials Network (CTN); the remaining portion of both regular and HIV-Initiative funding has been devoted to training and career awards. Since the launch of CIHR, the proportion of HIV/AIDS funding invested in health services and population health research has been growing, in keeping with CIHR's overall trends and reinforced by the HIV Initiative's targeting of emerging research areas, especially community-based research.

Training and salary awards

Since 2000, the HIV Initiative has supported 194 individual training and career awards, while CIHR's other training or career award programs supported a further 187 individuals working in areas relevant to HIV/AIDS research. The biggest growth areas overall have been in community-based research and health services/population health research (HS/PH). There has also been a major shift from funding established investigator salary awards to funding only new investigator awards, a change consistent with those to CIHR-wide salary support programs.

An interesting – though unexplained – finding is that, while only six of the 26 biomedical doctoral students funded up to 2004-05 have received any subsequent CIHR funding, the proportion in the HS/PH stream is nine out of 11. While there are insufficient data to determine whether the biomedical students are making effective use of their CIHR-supported training, it is clear that the HS/PH training stream is having a significant impact on building academic research capacity in these emerging fields.

Changes in research capacity

By any number of measures, there has been huge growth in HIV/AIDS research capacity in Canada since 2001. There are now three times as many investigators associated with HIV Initiative grants, and those researchers are now located in 55 institutions across Canada, up from 31 in 2001. There are about two-and-a-half times more Canadian HIV/AIDS authors publishing than there were in 2001. There has also been a large overall turnover in, and not just an addition to, the researchers. The HS/PH stream has experienced particularly large capacity growth, and almost two-thirds of its currently funded investigators are new to both CIHR and the HIV Initiative since the stream was transferred to CIHR in 2002.

Changes in productivity and quality of research

As would be expected from the increased funding and capacity, there has been, over the past 12 years, a roughly two-fold increase in the annual number of Canadian HIV/AIDS publications. Canada's share of this field is now consistent with its overall share of world health research, and Canadian investigators are now on average about 65 per cent more productive than a decade ago. In fact, four of the world's top ten most productive authors in the area of HIV/AIDS during 2006-08 were Canadian – twice as many as in 1996-98, when a still respectable two of the top ten were Canadian.

The quality of Canadian publications, as defined by citation rates, is well above world average. Both in 1996-98 and 2006-08, Canadian publications were the second-most highly cited in the world, suggesting our influence on the field of HIV/AIDS research outweighs our relatively small five per cent contribution of publications. Canada boasts 12 of the world's 100 most-cited papers for 2006-08.

Canadian HIV/AIDS research, relative to the rest of the world, is particularly focused on health services, social sciences and non-medical health professions. HS/PH publications per year have tripled since 1996, as compared to the doubling of HIV/AIDS publications overall. Canada's community-based research now constitutes eight per cent of the world's output in this area, almost twice Canada's average health research proportion, and is still rapidly rising. Although total numbers are too low to draw statistical conclusions, there has been a large increase in the quantity of Canadian publications related to HIV/AIDS and Aboriginal health and these are being cited more frequently.

Collaboration

Canadians have long been strong collaborators, working in large teams, with the average paper having almost six authors. In addition, some 45 per cent of papers with Canadian authors are actually foreign collaborations, and Canadians are seen increasingly to be taking a leadership role in these teams. Many particularly credit the CIHR Canadian HIV Trials Network (CTN) for making Canada a desirable and effective partner in international trials.

Improving health in Canada and internationally

Canadian HIV/AIDS researchers have a long history of working closely with research users, including community organizations, industry, regulators and other stakeholders. The success stories included in this report are testament to investigators who are passionately determined to see their findings applied to improve people's health, not merely have an academic impact. Canadian researchers are advancing the goals of the Federal Initiative to Address HIV/AIDS in Canada and improving health in Canada and internationally by helping to:

1. Prevent the acquisition and transmission of new infections through:
   • new international policies and funding for circumcision, which can prevent 50 per cent of transmissions;
   • implementing "treatment as prevention", which could reduce new HIV cases by 95 per cent within 10 years; and
   • developing vaccines and discovering the nature of natural immunity to HIV.
2. Slow the progression of the disease and improve the quality of life through:
   • developing/testing new drugs and treatment strategies, including 3TC and the "triple cocktail" approach;
   • identifying the best treatment strategies, including when to start and whether interruptions are safe; and
   • discovering how HIV pathogenesis works and new avenues for HIV cure, and not just control.
3. Reduce the social and economic impact of HIV/AIDS through:
   • reducing disability and improving quality of life and ability to work through better treatment;
   • reducing transmission to save thousands of lives and millions of dollars; and
   • developing community-based research to reduce risky activity in heavily affected communities.
4. Contribute to the global effort to reduce the spread and mitigate the impact of HIV through:
   • advocating for better prevention and treatment approaches around the world; and
   • building world-acclaimed partnerships between developing and developed country research teams.

Introduction

History of Government of Canada HIV/AIDS research support

The Canadian Institutes of Health Research (CIHR) manages the research components of two major Government of Canada HIV/AIDS initiatives: the Federal Initiative to Address HIV/AIDS in Canada and the Canadian HIV Vaccine Initiative. CIHR also invests significant funds in HIV/AIDS research through its open grants and awards, and through other related strategic initiatives (Figure 1).

Federal Initiative to Address HIV/AIDS in Canada

The Federal Initiative to Address HIV/AIDS in Canada (FI) was announced on January 13, 2005, following on from the previous Canadian Strategy on HIV/AIDS, which began in 1997. The Federal Initiative is a partnership between the Public Health Agency of Canada, Health Canada, the Correctional Service of Canada and CIHR. The overall objectives of the Initiative are to:

1. prevent the acquisition and transmission of new infections;
2. slow the progression of the disease and improve quality of life;
3. reduce the social and economic impact of HIV/AIDS; and
4. contribute to the global effort to reduce the spread of HIV and mitigate its impact

The Federal Initiative evolved from the Canadian Strategy on HIV/AIDS, which provided dedicated HIV/AIDS research funding to CIHR's predecessor, the Medical Research Council, of up to $5.5 million/year for biomedical and clinical research. These funds were transferred to CIHR on its creation in 2000.

An additional three funding streams were originally administered by Health Canada's National Health Research and Development Program (NHRDP): $3.2 million in research infrastructure to support a Canadian HIV Clinical Trials Network; the epidemiology and public health research stream, for which $2.4 million was allocated; and the Community-Based Research Program (CBR), supported by $1.8 million. When the NHRDP was subsumed by CIHR in 2001, responsibilities for the investment of the HIV/AIDS-related epidemiology and public health research stream and the administration of the Canadian HIV Trials Network were transferred to CIHR so that, by 2001-02, CIHR was responsible for about $10 million/year of Strategy funds; this is the baseline year that has been used for many of the funding and capacity comparisons with the most recent complete fiscal year (2008-09). In April 2004, the CBR Program was transferred from Health Canada to CIHR. This Program funds capacity-building initiatives and research projects in two streams - General and Aboriginal research.

Canadian HIV Vaccine Initiative (CHVI)

The Canadian HIV Vaccine Initiative (CHVI), announced in February 2007, is Canada's contribution to the Global HIV Vaccine Enterprise. A collaboration between the Government of Canada and the Bill & Melinda Gates Foundation, CHVI represents an enhanced Canadian contribution to global efforts to develop an HIV vaccine. CIHR will contribute $10 million over five years (2008-2013) to support Discovery and Social Research focussed on the discovery of HIV vaccines and related issues (e.g. mucosal and innate immunity) and social and behavioural issues around HIV vaccines (e.g. accessibility to, and acceptability of, vaccines and cultural and other sensitivities to HIV vaccine use).¹ Because this particular initiative only began in 2008, we cannot report on any impacts, only on activity. In early 2008, a consultation on CHVI Funding programs was held in Ottawa, attended by about 80 national and international experts and stakeholders. It was agreed that the key objectives of the Discovery and Social Research component were to:

• create internationally recognized teams of Canadian researchers and those from lower- and middle-income countries (LMICs);
• support individual or small teams of Canadian investigators in their efforts to contribute important knowledge to the global search for HIV vaccines;
• build capacity for HIV-vaccine research in Canada and LMICs; and
• mechanisms for CHVI investigators and teams to collaborate with one another and with other relevant international networks and consortia.²

There was also a consensus that the best way forward was a combination of individual and team-based funding. Accordingly, as of March 2010, CIHR has developed a number of funding opportunities:

• a Travel Grant to encourage Canadian researchers to attend a CHVI-led partnership forum with LMIC researchers at an international HIV Vaccine meeting (through which six grants were funded) ($50,000);
• two launches of Operating Grant Priority Announcements (through which five grants were funded) (~$2 million);
• three launches of Catalyst Grants (through which eight grants were funded with one competition currently underway) (~$800,000); and
• an Emerging Team Grant launch (applications under review at this time) (~$2.5 million).

With the exception of a planned Large Team Grant RFA, CIHR has delivered on all of its planned CHVI funding programs.

CIHR management of the Federal Initiatives

CIHR's Institute of Infection and Immunity manages the Federal Initiative funds allocated to CIHR with guidance from the CIHR HIV/AIDS Research Advisory Committee (CHARAC). This committee brings together many CIHR Institutes, various HIV/AIDS research pillars, government and HIV/AIDS community organizations. In addition, the Community-Based Research (CBR) Program also has its own steering committee, composed of both general and Aboriginal researchers and community members. The CIHR Institute of Aboriginal Peoples' Health plays a supportive role in the Aboriginal research stream of the CBR Program.

In 2007-08, CHARAC led a consultation process to develop a strategic plan for CIHR's HIV/AIDS Research Initiative. This plan, entitled "Canadian Institutes of Health Research HIV/AIDS Research Initiative Strategic Plan 2008-2013", sets out six priority research themes, with which all HIV/AIDS research support programs will be aligned. The priority themes are:

• Health systems, services and policy
• Resilience, vulnerability and determinants of health
• Issues of co-infection and co-morbidity
• Drug development, toxicities and resistance
• Pathogenesis
• Prevention technologies and interventions

Objectives of this analysis

This analysis was undertaken in response to CIHR's desire to identify the most significant health and research impacts of the Canadian investment in HIV/AIDS research. It wanted to know what Canadians have received from their investment in terms of: new knowledge; improved approaches to prevention, treatment and care; and new products and services.

The specific objectives of this assessment were to:

1. Identify Canada's most significant HIV/AIDS research achievements and their impacts.
2. Identify Canada's most important contributions to global HIV/AIDS efforts; determine changes in Canada's international standing over the duration of the Initiative.
3. Examine trends in research activity and productivity with respect to HIV/AIDS research in general as well as the priority areas of the Initiative.

In the following report, we have thus assessed the impacts of Canada's HIV/AIDS research investments on building research capacity and on increasing the productivity and impact of Canadian research. We highlight some of Canada's key research achievements and their outcomes (see text boxes), as identified by key research, practice and community leaders, and combine this with quantitative analysis of funding, capacity building and research performance, using publication and citation data.

Both capacity building and research achievements require long-term investments on the part of both researcher and funder. The outcomes described in this report have all been catalyzed by extensive and extended support from CIHR's research strategies and Government of Canada initiatives. However, Canada's top HIV/AIDS researchers have justifiably attracted funding from a wide range of other Government of Canada, provincial, charitable and international sources as well; it would be neither possible nor appropriate to attribute the success of these extraordinary people to any one funding source. Instead, we are pleased to describe the remarkable successes that Canadians have achieved, collectively, through their investments in HIV/AIDS research. Major international funding won by Canadian researchers would not have been possible without prior investment from Canada.

Funding for HIV/AIDS research

CIHR funding mechanisms for HIV/AIDS

Since its origin in 2000 up to and including fiscal year 2008-09, CIHR has invested a total of $278 million in HIV/AIDS research: $134 million through its CIHR HIV/AIDS Research Initiative (HIV Initiative) and $150 million in other CIHR funding. Investment by fiscal year is shown in Figure 1. The HIV Initiative has received significant support throughout this period from earmarked Government of Canada funds for HIV/AIDS research, as well as from the CIHR base budget. The HIV Initiative funding is distinct from "other" CIHR funds, which were awarded in open (untargetted) competitions and happen to be in the area of HIV/AIDS by virtue of the interests of the grant or award recipient. The "other" category³ includes an enormous range of CIHR funding programs.⁴ However, by far the greatest single type of investment ($51 million) has been in the form of Open Competition Operating Grants, which are intended to "support original, high-quality projects proposed and conducted by individual researchers or groups of researchers, in all areas of health".⁵ HIV/AIDS-related proposals were reviewed by 34 of CIHR's 55 open competition review committees, testifying to the range of research funded, including five grants in the area of ethical and legal issues.

Throughout the history of CIHR, biomedical research has been the largest beneficiary of CIHR spending on HIV/AIDS, but the proportion of funding devoted to biomedical research has decreased over time within the HIV Initiative funding envelope (Figure 2),⁶ due to a greater expansion of research in the themes of Social, Cultural, Environmental and Population Health (SCEPH in Figure 2) and Health Services and Systems research (HSS). In the "other" CIHR funding, there has been a marked increase in funding in both absolute and relative terms for research in the SCEPH theme and for biomedical research. The proportion of funding supporting HSS and clinical research has decreased.

HIV Initiative investment also has been primarily in various forms of operating grants (Figure 3A), which provide the materials, supplies and technical support necessary to perform research projects. The second-largest investment has been the continuing support for the CIHR Canadian HIV Trials Network (CTN), and significant amounts have also been committed to training and to support of career investigators. The allocation to the Canadian HIV Vaccine Initiative is recent, and so represents only a small fraction of the total investment since 2000 (Figure 3B).

Figure 1 CIHR spending on HIV/AIDS research (includes Canada Research Chairs and NCE funding)

Figure 2 CIHR spending on HIV/AIDS by research Theme (Canada Research Chairs and NCE funding omitted)

Figure 3A HIV Initiative funding program type

Figure 3B HIV Initiative funding by stream

Other funding for HIV/AIDS research in Canada

Other Government of Canada funding has also supported the development of HIV/AIDS research in recent years. Canada Foundation for Innovation (CFI) grants (1998-2009) relevant to HIV/AIDS total $15 million, resulting in a total investment in infrastructure by CFI and its provincial and institutional partners of $37.5 million. Forty-seven Canada Research Chairs are working in relevant areas. The Natural Sciences and Engineering Research Council (NSERC) has made 53 relevant awards since 2000, mostly for studentships, worth $1.3 million. Social Sciences and Humanities Research Council (SSHRC) grants and awards over the same period total $3.5 million. While no Genome Canada funding is specifically earmarked for HIV/AIDS research, the regional genome centres and other proteomics and genomics platforms have also facilitated HIV/AIDS research. For example, the Ontario Genomics Institute reports a $10 million project to develop new antiviral agents for HIV in collaboration with industry.⁷

Many provincial governments support HIV/AIDS research through their own health research organizations. For example, since 2001, the Michael Smith Foundation for Health Research in B.C. has supported 12 Career Investigators working in areas relevant to HIV/AIDS, as well as 26 trainees. The largest dedicated provincial contribution is through the Ontario HIV Treatment Network, which invests $5-6 million/year in operating grants, community-based research, salary and training awards and a large cohort study. In the charitable sector, the Canadian Foundation for AIDS Research (CANFAR) provides operating grants, but its funding has steadily decreased since the early 2000s. In 2002-03 it provided $1.5 million in funding, but only provided $765,000 in the current year.

There is also significant funding from foreign sources. Since 2002, the Bill and Melinda Gates Foundation has invested US$55.5 million in HIV/AIDS grants at Canadian institutions, including $23 million to the University of Manitoba in 2003 "to scale up effective programs for the prevention of HIV and other STIs in India".⁸ Two additional Grand Challenges Explorations grants relevant to HIV/AIDS research were awarded to Canadians in October 2009. The National Institutes of Health has regularly funded between four and ten grants each year to investigators at leading Canadian institutions. In the current fiscal year, 2009-10, there are six awards, all to the University of British Columbia, totalling US$2.07 million. Nevertheless, the predominant and consistent source of support for HIV/AIDS funding in Canada is CIHR.

Complementarity of CIHR funding mechanisms

Since CIHR funds HIV/AIDS research both through its open competition funding, where applications compete with those from other fields of research, and from the HIV Initiative funding, we thought it important to see if the two approaches are supporting the same cohort of investigators. We identified 235 individual principal investigators receiving grants considered relevant to HIV/AIDS through the CIHR open operating grants competitions. Only 19 per cent of these had also received operating grants through HIV Initiative funding. A sampling of the open-competition grant summaries shows that many of these grants are indirectly or peripherally related to HIV/AIDS, rather than HIV/AIDS being the primary focus of the project. Thus, the two forms of funding are complementary, furthering the research of largely different populations of researchers with largely different aims.

Looking at the figures more closely, only 12 per cent of principal investigators funded through the CBR stream of the HIV Initiative have ever received an open operating grant from CIHR as a principal investigator. For comparison, 58 per cent of the principal investigators funded through the biomedical stream of the HIV Initiative have received an open operating grant as principal investigator. This finding emphasizes the importance of the CBR stream. Without it, it is unlikely that the work it supports would be funded by CIHR, either because such projects would not be competitive according to the criteria for adjudication in the open grants competitions, or because applicants working in this area would not consider applying to CIHR for open competition funding; these two possibilities are closely related.

The primary goal of the CBR Program has been to build research capacity, a need reinforced by the fact that the vast majority of those funded under this program had not been previously funded by CIHR as principal investigators. Given that most of these investigators are relative newcomers to CIHR funding, we should not yet expect a mature level of research productivity and practical impacts from this emerging research area.

Commercialization and industry-partnered funding

Figure 4 CIHR investment in HIV/AIDS within Industry-partnered and Commercialization Programs

There has been significant investment by industrial partners in HIV/AIDS research funded by CIHR. Figure 4 shows the CIHR investment by year in various industry-partnered and commercialization funding programs, totalling $3 million between 2000 and 2009. Because the matching industrial partner contributions required for the programs vary, it is not possible to calculate the amount of the industrial contribution, but it would be at least twice the CIHR investment, or approximately $6 million.

There has been a step-increase in this type of funding in recent years, with several large grants dealing with new therapeutic and diagnostic products supported through the Proof of Principle commercialization program, which began in 2003, and through the Small and Medium-sized Enterprise Partnership Program. The reason behind this increase is obscure.⁹ We expect that industry co-investment in CIHR HIV/AIDS research will increase further as the Canadian HIV Vaccine Initiative (CHVI) ramps up. Academic-industry teams are encouraged to apply to the current request for applications in support of new emerging teams that will work on the discovery of HIV vaccines and social, behavioural and ethical issues related to HIV-vaccine use and research.¹⁰

Who is funded by CIHR?

Although CIHR is the predominant Canadian funding source, the only sure way of attributing a particular publication to the funding provided by the HIV Initiative or CIHR generally is to read the publication and note the funding sources acknowledged.¹¹ This is highly time-consuming; we have, therefore, been selective in such an examination. We found that of the 20 most-cited HIV/AIDS publications with Canadian authors in 2006-08, only five directly acknowledged CIHR funding. While this seems low, we note that many of these other highly cited papers are therapeutic trials sponsored by pharmaceutical companies or secondary research communications (reviews, guidelines), where direct research support is seldom acknowledged. However, the Canadian authors of every one of these most influential papers received major research funding from CIHR.

When we focused on authors, rather than publications, we again found essentially complete coverage of CIHR support. We identified 23 Canadian authors who were credited with three or more publications each among the top 100 most-cited papers with Canadian authors over the period 2000 to mid-2009. Twenty out of 23 of these "most-cited" authors had received CIHR funding, and the three exceptions worked in large groups whose leaders were well-funded by CIHR.¹²

We conclude that CIHR's investment in HIV/AIDS research supports all the researchers in Canada who publish the most-highly cited work. Of course, this relationship is more than coincidental: CIHR support enables these individuals to conduct high-quality research and, because they publish highly cited papers, their exemplary publication records assist them in securing subsequent competitive CIHR funding.

Capacity-building

Investment in training and salary awards

Overall, the number of trainees and investigator awards¹³ supported by the HIV Initiative has been steadily increasing each year (Figure 5). Within that growth, however, there are some specific shifts in emphasis. For example, while the number of biomedical/clinical studentships reached a plateau in 2005-06, the Community-Based Research (CBR) and Health Services/Population Health Research (HS/PH) streams are continuing to grow. Fellowship awards grew significantly in both the biomed/clinical and HS/PH streams from 2005-06 onwards.

Figure 5 Value of Training and Salary Awards supported by HIV Initiative funds each year

Salary awards have declined slightly in terms of investment. There has been an important change in focus of salary awards since the beginning of CIHR, when all the awards inherited from MRC were for established investigators. Now, all CIHR salary awards support new investigators. In all, the HIV Initiative funds have supported 194 individual training and salary awards; a further 187 individuals have received CIHR awards from other funding programs for training or salary support relevant to HIV/AIDS research (Table 1).

Table 1. Number of individual awards (2000-01 to 2008-09)

	HIV Initiative	Other CIHR
Studentship	113	94
Fellowship	60	38
Salary (Career)	21	35
subtotal	194	187
Total	381

Number of Investigators Supported

CIHR's HIV Initiative has attracted more than a three-fold increase in the number of investigators it supports through grants each year,¹⁴ from 152 in 2001-02 to 472 in 2008-09 (Figure 6) (some individuals may hold more than one grant; with these duplicates removed, the number of funded individuals in 2008-09 was 398). We can similarly see significant capacity growth in the number of Canadian authors publishing in the research literature. Since the inception of CIHR, the total number of individual authors in a year's publications (in this case restricted to original research reports) has risen from about 1,000 to more than 2,300. Within that broad group, the "core" community of researchers – those publishing more than one paper a year in this field – has grown from around 140 to more than 350 in 2008.

Figure 6 Number of investigators receiving grants through HIV Initiative

Where are the added investigators coming from?

The increased number of funded investigators may be due to the attraction of established investigators who were previously working in other fields of research into HIV/AIDS research (this is a valid reason for establishing targeted funding for priority areas), or to new recruits to CIHR funding.

Biomedical/Clinical stream
In 2008-09, there were 141 individual biomedical investigators¹⁵ receiving funding from the HIV Initiative, a 204 per cent increase from the 69 receiving funding in 2001-02. Ninety-two of those funded in 2008-09 were also funded by CIHR in 2001-02, either through the HIV Initiative or CIHR's other funding programs (principally open operating grants), but 37 of the 92 were not working on HIV/AIDS relevant projects at that time, and have subsequently moved into the area. Thirteen of the 141 were CIHR-funded trainees in 2001-02. Forty-nine of those funded in 2008-09 were "new recruits", that is, not receiving any grant or training funding from CIHR in 2001-02. Clearly, HIV Initiative funding has built considerable net biomedical research capacity in the form of 49 new and 37 established recruits to the field (Figure 7). A considerable turnover of investigators is evident from the fact that only 27 of the 69 investigators funded through the biomedical stream of the HIV Initiative in 2001-02 were so funded in 2008-09. Out of a sample of 20 of those no longer funded from the HIV Initiative, 60 per cent had CIHR grant funding from other sources, mostly open operating grants, and two-thirds of these were continuing to work on HIV/AIDS problems.

Health services/Population health stream
Since the HS/PH stream was transferred to CIHR in 2001, the growth in capacity has also been significant. Overall, 92 (62 per cent) of the 149 investigators funded in 2008-09 were "new recruits", not funded by CIHR in 2001-02. In addition, 22 established investigators, funded by CIHR in 2000-01 for work in other areas, have moved into the HIV/AIDS field, resulting in an overall gain in capacity of 114 investigators (Figure 7). Eight of the 149 were CIHR-funded trainees in 2001-02. There has been an even more dramatic turnover of investigators in this area than in the biomedical stream: only 18 of the 83 funded through the HS/PH stream in 2001-02 (as noted in figure 6) were so funded in 2008-09. Out of a sample of 20 investigators no longer funded from the HIV Initiative, 45 per cent had CIHR grant funding from other sources, mostly open operating grants, and half of them were continuing to work on HIV/AIDS problems.

The CBR streams, general and Aboriginal, overwhelmingly involve investigators working in the CIHR theme areas of health services, and social, cultural and environmental health. After adding these individuals to those supported by the HS/PH stream, there has been a growth from 83 to 279 individuals (336 per cent) since 2001-02.

Figure 7 History of Investigators funded in 2008-09

Another dimension to capacity-building is geographical. In 2001-02, CIHR funds from the HIV Initiative flowed to only 31 institutions. In 2008-09, 55 institutions and organizations were funded (Figure 8), including organizations with a national scope, reaching into all provinces and territories.

Figure 8 Distribution of institutions and organizations receiving HIV Initiative funding in 2001-02 and 2008-09

Where are the trainees going?

A significant fraction (seven per cent) of the CIHR support for HIV/AIDS research through the HIV Initiative has been invested in training awards, anticipating that those receiving them will continue to work in the field of HIV/AIDS research and so contribute to the mitigation of the disease. Assuming that trainees who continue to be active in research in an academic setting will continue to apply to CIHR for funding, we examined the CIHR funding database for subsequent grants and awards to those who received training awards through the HIV Initiative.

Biomedical/Clinical stream
The vast majority of the biomedical-clinical trainees are not "retained" to receive subsequent CIHR funding. Only six of the 26 doctoral students funded up to 2004-05 have received any subsequent CIHR funding (such as post-doctoral fellowships or operating grants); three of the six are no longer working in the HIV/AIDS area. The proportion is also low for post-doctoral fellowships: seven of the 35 biomedical/clinical post-doctoral fellows funded up to 2006-07 have gone on to receive various types of operating grants (two were in other areas of research). Multiplying these ratios¹⁶ suggests that as few as five per cent of the biomedical students supported by the HIV Initiative are retained to receive CIHR grant funding.

Health services/Population health stream
In contrast to trainees in the biomedical/clinical stream, former HS/PH trainees are more active within the CIHR-funded HIV/AIDS research community. Nine of the 11 doctoral students, and three of the six post-doctoral fellows, funded up to 2004-05, have received subsequent funding, all except one for HIV/AIDS research. Multiplying these ratios gives a retention rate of 41 per cent. The HS/PH training stream is clearly having significant impact on building academic research capacity in these emerging fields.

There is a striking difference in apparent retention within the cadre of researchers funded by CIHR of the HS/PH trainees as compared to the biomedical/clinical ones. Since neither the career goals nor the ultimate destination of the trainees are known, we cannot say whether the differences represent a failure of academic retention, or great success in effectively equipping biomedical trainees for careers outside academia, in industry, government, or the health professions.¹⁷ A tracking study of the fates of trainees is warranted.

Research productivity

Productivity and research funding

We would expect that, as the funding for HIV/AIDS research increased, there would be increased numbers of research publications in the years following. We found that the doubling of 2000-01 funding was followed by only a very small increase in numbers of publications but, after funding rose even further, publications subsequently rose steeply in number.¹⁸ Since the publication output per dollar funding input is continuing to rise, the full capacity of the Canadian HIV/AIDS research community to generate publishable research findings does not seem to have been reached.

Canadian research productivity¹⁹

For funding data, we have used 2001-02 as the "baseline" year for most analyses, as this is the earliest year for which we have reliable data. In contrast, reliable publication data are available for earlier years, and so we have used 1996 as the baseline year, because this is prior to the start of the HIV Initiative. Annual publications in HIV/AIDS that had at least one author with a Canadian address ("Canadian publications") increased at least two-fold between 1996 and 2008, while total world publications in HIV/AIDS increased about 1.2-fold. As a result, the Canadian share of world publications in HIV/AIDS increased significantly.

Table 2 HIV/AIDS Publications retrieved from different databases

	PubMed	WoS	Scopus
Canadian publications in 1996	190	372	412
Canadian publications in 2008	468	746	813
Increase 2008/1996 %	2.46	2.00	1.97
World publications in 1996	12491	11263	15542
Canada's share %	1.52%	3.30%	2.65%
World publications in 2008	15136	14845	17935
Canada's share %	3.09%	5.03%	4.53%

Pub Med: US national Library of Medicine; WoS=Web of Science ® (Thomson-Reuters); Scopus^TM= Elsevier B.V.

Some of the differences between the numbers of publications retrieved from each database are easily explained.²⁰ One difference, however, is probably not merely technical. Note that the number of PubMed "hits" between 1996 and 2008 increases more than those in the other two databases, as does Canada's publications as a percentage of the total. This means that there was a greater increase in publications where first authors were Canadians than for all publications (where Canadians might be collaborators with lead authors from other countries), suggesting that increasingly Canadians are taking a leadership role in international collaborations.

When these publication numbers are plotted out as a time-series (Figure 9), it is evident that the growth in publication numbers, and in Canadian world share, has occurred essentially since 2001, following the establishment of CIHR in 2000 and the subsequent increased funding available through both CIHR open competitions and the HIV Initiative, as well as other Government of Canada investments, such as CFI.

Figure 9A (left) Annual number of Canadian HIV/AIDS publications retrieved from the three databases; Figure 9B (right) expressed as a percentage of world publications

Health services/Population health stream
The productivity in the HS/PH stream (Figure 10) matches its remarkable capacity-building. Both have particularly increased in the last four years (Figure 6), suggesting the productivity of this group is still on an upward trend. HS/PH publications have tripled since 1996, as compared to the doubling of HIV/AIDS publications overall (Figure 9A).²¹

Figure 10 Canadian publications in Health Services and Population Health related to HIV/AIDS (columns= WoS and lines=Scopus)

Community-based research
Canadian CBR publications (Figure 11) increased sharply in 2005, and are continuing to increase.²² Canadian share of world publication has increased markedly from about four-to-five per cent in the early 2000s to just under eight per cent today. Canadian CBR publications have a world share almost twice as large as Canada's share of HIV/AIDS research overall (Table 2).

Figure 11 Publications/yr. in CBR-relevant areas of HIV/AIDS research

Figure 12 Publications in HIV/AIDS relevant to aboriginal people's heatlh

CBR sub-stream on Aboriginal health
Canada is making major contributions to the very small global literature on Aboriginal health.²³ With support from the Aboriginal funding sub-stream of the CBR Program, Canadian productivity in the years 2005-08 was almost four times higher than in 1996-2001; Canadian world share has risen from 13 to 28 per cent over the same interval. Canadian productivity increased from 2002 onwards, while worldwide productivity, previously quite erratic, began a consistent increasing trend a year later (Figure12).

Productivity of elite investigators

The Canadian elite of HIV/AIDS researchers has also become much more productive. In 1996-98 the average productivity of the top 40 investigators was 16.5 papers in three years; by 2006-08, this number had risen to 25.8. The median productivity similarly increased from 12 to 20 papers over three years. Put another way, the productivity of the 15th-ranked author in 1996-98 (13 publications) would have earned only 40th place in 2006-08.

As we would expect from the history of grant recipients reported in the capacity-building section, there has been significant turnover and addition of "new blood" to this elite. Of the 40 most productive Canadian authors publishing in 1996-98, only 11 remained in this elite in 2006-08; conversely, 29 of the top 40 in 2006-08 were not in the 1996-98 elite.

International comparisons of productivity²⁴

Canada's relative productivity is also increasing. In 1996-98 Canada was in sixth place internationally in terms of publication numbers but, by 2006-08, Canada had moved to fourth place, displacing Italy and Germany, whose publication numbers have barely increased. Also noteworthy in 2006-08 are the appearance of China and South Africa among the top HIV/AIDS research nations; while Canada's production increased 1.7-fold between the two time periods, South Africa's increased six-fold, and China's 13-fold. The extraordinary dominance of the United States in this, as in all areas of health research, continues unchallenged; numbers for American publications are well off the top of the chart in Figure 13.

Figure 13 Canada's publication record in HIV/AIDS relative to other leading countries

Trends in focus of Canadian research²⁵

The focus of HIV/AIDS research publication in Canada has changed from an overwhelming preponderance of biomedical and clinical approach to one that includes a greater proportion of social science, population health (including public health) and health services research. Between 1996-98 and 2006-08, social-sciences publications increased from 8 per cent to 13 per cent of the total, population health from 8 per cent to 11 per cent, and health services from 3 per cent to 6 per cent with a corresponding decrease in "other health" from 69 per cent to 60 per cent (Figure 14). (This large category, which amounted to 52 per cent of the 2006-08 total publications, includes all biomedical and clinical research in infectious diseases, virology and immunology, as well as other clinical medicine specialities.)²⁶ This shift parallels both the overall evolution of research funded by CIHR, and the history of the research streams supported with HIV Initiative funding.

Figure 14 Distribution of Canadian publications in HIV/AIDS by broad field of research.

Areas of Canadian research specialization
Canada is an important contributor to the world research literature in HIV/AIDS, but are there any particular areas where Canada specializes? For the largest fields in terms of publication numbers (infectious diseases, immunology and virology), Canada's index of specialization²⁷ is close to one (Figure 15), i.e., Canada produces as many publications in this field as one would expect from its overall contribution to the world literature. However, Canadian researchers over-contribute (index >1) in the areas of health services, social sciences and non-medical health professions (nursing, rehabilitation), and under-produce (index <1) in microbiology and physical sciences. This latter grouping includes disciplines such as organic and medicinal chemistry and may be a reflection of the low level of industrial pharmaceutical research in Canada.

Figure 15 Index of specialization of Canadian publications in HIV/AIDS (2006-08), by research field

Quality of Canadian research publications

While Canadian researchers publish a lot of papers, how "good" are they? Canada's HIV/AIDS research output was, and is, excellent. Quality in bibliometric terms is synonymous with citations: a quality paper is one that is cited by other authors in their publications, on the assumption that it is cited because it provides important conceptual, factual or technical foundations for the work reported in the citing paper. Using this indicator, Canadian research in HIV/AIDS compares very well internationally. For 2006-08, Canadian publications ranked as second-most cited (Figure 16), with the UK in first place and the US in fourth. For 1996-98 publications, Canada also ranked second, with the US first.²⁸

Figure16 Average number of citations per paper for 2006-08 HIV/AIDS publications from leading countries.

The overall impact of a particular set of publications (from a single author, journal, institution or country) can be expressed as its h-index,²⁹ which is also derived from citation analysis. Canada is in fourth place overall (Figure 17). In terms of overall influence on the field of HIV/AIDS research, the high quality of Canadian publications is offset by the lower number, as compared to, for example, the US and UK.

Figure 17 h-index for the leading nations in HIV/AIDS research (2006-08)

Subfields of HIV/AIDS research

With respect to performance in subfields of HIV/AIDS research, Figure 18 shows that Canadian papers are cited at above-average frequencies in all fields analyzed, except public and population health, where Canada is at the world average. It may be that this area of HIV/AIDS research, which has shown great recent growth, may need some more time to mature and be widely cited. The superior citation record also applies to the papers published in 1996-98, when Canadian publications were predominantly in the biomedical sciences.

Figure18 Citation frequency for Canadian and World HIV/AIDS Publications in various research fields (Inf Dis = infectious diseases; HSR = health services research)

Aboriginal health stream
Because the numbers are so small, we must be cautious in drawing firm conclusions from the citation data for Aboriginal health publications. As can be seen in Table 3, the citation data for 1996-98 are quite erratic, with a tiny overall body of work and a few papers being cited constantly, likely as a result of limited competition as much as the inherent quality of the papers. By 2006-08, however, the body of work had grown to a more significant size; citation data shows less extreme variation,³⁰ and is likely much more meaningful. Canada's citation rate is now quite consistent with that of other leading countries. This suggests that the quality of Canadian work in this field has recently improved and is now internationally competitive. The overall international citation rate of around 3.0 is consistent with population-health publications more broadly.

Table 3 Citations of Aboriginal People's Health publications in HIV/AIDS (WoS data) from the five leading countries

Country	1996-98		2006-08
	publications	citations/paper	publications	citations/paper
UK	6	63.17	11	2.55
USA	9	35.08	37	3.97
Switzerland	2	23.5	0	0
Australia	11	8.55	12	3.67
Canada	9	4.44	32	3.66
South Africa	0	0	14	2.5

Most-cited publications

Canadians are also increasing their presence among the world's most-cited publications. Only four of the world's most-cited papers from 1996-98 had Canadian authors (Figure 19); Canada's best ranked 57th. In 2006-08, however, Canadians were authors on 12 of most influential 100 publications from 2006-08, including three of the "top 20". Canada's best ranked second.

Figure 19 Citation frequency for world top 100 publications: those with Canadian authors in dark shade.

Most-productive authors

Canadians are remarkably well-placed among the most productive authors in the field, particularly considering that Canada produces only four-to-five per cent of the world's HIV/AIDS publications. In fact, four of the world's top ten authors for 2006-08 publications were Canadian (Figure 20), twice as many as for 1996-98 publications, when a still respectable two of the 10 were Canadian.³¹

Figure 20 World's most productive researchers (2006-08): Canadians in dark shade.

Collaborations

Comparing the number of publications to the number of authors shows that, in common with many other fields of health research, there has been a tendency to publish as larger collaborative teams. A count of 500 randomly chosen papers shows that, in 1996-98, the average HIV/AIDS paper had 5.0 authors. By 2008, this had risen to 5.9. This is less of an increase than in many other fields of health research (the comparable values for all Canadian health research papers are 3.9 and 5.3), showing that the HIV/AIDS research community has long been highly collaborative.

International collaboration

International collaboration has always been a strong feature of the Canadian HIV/AIDS research community and, in common with other areas of health research, such collaboration has increased in recent years. From the WoS database, the number of foreign collaborations equalled 50 per cent of all Canadian publications in 1996-98 and 82 per cent in 2006-08. While these very high percentages are artefacts of collaborations involving more than one country, which are counted multiple times,³² the relative increase makes the point. From inspection of a random sample of 200 publications, the true fraction of Canadian publications that are foreign collaborations is 30 per cent for 1996-98 and 45 per cent for 2006-08 publications. The major countries with which Canadian authors collaborate are shown in Figure 21. Collaboration has increased significantly with the US, UK, Germany and Spain and most notably with India, Peoples Republic of China, South Africa and Uganda.

Figure 21 Countries with which Canadian authors are collaborating in HIV/AIDS research

Among the 100 most-cited HIV/AIDS clinical trials whose results were published between 2004 and 2009, Canadian authors were involved in ten, and nine of ten of these papers were international collaborations.

Collaborating with knowledge users

Canadian HIV/AIDS researchers have a long history of working closely with users of the new knowledge derived from research, including community organizations, industry, regulators and other stakeholders. The success stories included in this report are testament to investigators who are passionately determined to see their findings improve people's health, and are not content just to write academic publications.

While knowledge translation (KT) activities were not a requirement for investigators funded originally through the HIV Initiative, KT lies at the core of many of its programs. For example, from its inception, the CIHR Canadian HIV Trials Network (CTN) has been led by Canada's top clinicians, has integrated people living with AIDS into all its decision-making processes and has worked in close collaboration with regulators and industry. All these partnerships help ensure that the CTN is doing the right research at the right time, and that its results will be readily taken up by those who can use them.

Another important example is community-based research. CBR is effectively integrated KT "in action", an approach that ensures that knowledge transfer and research uptake are a core and continual part of the research process.

In addition, all CIHR funding for targeted KT activities related to HIV/AIDS research has ramped up steeply, from seven grants worth $185,000 in 2005-06 to 28 grants worth $539,790 in 2008-09.

In the future, KT efforts are increasingly expected of new HIV/AIDS funding recipients. For example, applicants to the Emerging Team Grant: HIV/AIDS Vaccine Discovery and Social Research opportunity (under review) are expected to "develop strategies for knowledge translation",³³ and the Centres for Population Health and Health Services Research Development in HIV/AIDS, of which two were recently funded, will "support the translation of knowledge in various target populations in order to increase the impact of research on policy and practice with relevant stakeholders".³⁴

This enhanced focus on KT will help ensure that Canadians get the maximum benefits from their investments in HIV/AIDS research.

Public awareness

CIHR's investment in HIV/AIDS research, through the HIV Initiative and its other funding, has generated a great deal of media attention. A search of news and other publication archives revealed 99 English- and 27 French-language news articles, 41 CIHR releases and newsletter items, and eight Government of Canada releases since the launch of the renewed Federal Initiative to Address HIV/AIDS in Canada in early 2005.³⁵ During 2006-08, five-to-six per cent of the annual CIHR news articles reporting on research discoveries and awards were related to HIV/AIDS. The greatest publicity was given to a CIHR/NIH-funded study conducted in Kenya by Dr. Stephen Moses (University of Manitoba) and colleagues, which found that circumcised men were significantly less likely than uncircumcised men to acquire HIV during heterosexual sex. This finding was rated the top medical breakthrough of 2007 by Time magazine.³⁶

The news items have covered the range of research activities supported through the HIV Initiative. An examination of the 28 individual "stories" still available in various media archives (and therefore not a rigorously representative sample) showed that 46 per cent of the stories related to biomedical research (such as vaccine studies), 29 per cent to population health (including prevention strategies), seven per cent to health services and four per cent (one story) to clinical research. The remaining 14 per cent of stories were focused on individuals or agencies (e.g. the Canadian HIV Vaccine Initiative).

Conclusion: Research contributions to the Federal Initiative to Address HIV/AIDS in Canada

CIHR's investments in capacity building and research support, through the HIV Initiative and other funding, have made major contributions to achieving the four goals of the Federal Initiative to Address HIV/AIDS. In the sections below, we identify how the key achievements featured in this report have contributed to each of these goals.

The Canadian success stories included in this report are those that were universally identified as seminal by the research leaders and others we contacted. There are, however, many other achievements having significant impact at more local levels, and many up-and-coming researchers whose work could soon demand similar levels of international respect. The recent work of Canadian researchers – most of them supported by CIHR and/or HIV Initiative funds – is ranked second worldwide in terms of citation impact (Figure 16). This degree of influence is a remarkable achievement for a scientifically small country producing only five per cent of the world's store of knowledge in HIV/AIDS research. Moreover, thanks to the generous funding through the Federal Initiative to Address HIV/AIDS, the indicators described in this report suggest that the trend will continue upwards, ensuring Canada's continuing contribution to reducing the toll of HIV/AIDS worldwide.

Goal 1: Prevent the acquisition and transmission of new infections

One of the most striking aspects of Canada's HIV/AIDS researchers is their integration, both in how well-connected their research activities are to each other, and also in the multidimensional approaches they take to fighting this very complex disease. For example, Mark Wainberg may be world-renowned for his studies of the molecular basis for drug resistance, but he has also taken to the streets to ensure that people are benefitting from what his research team is learning. They have recently demonstrated, through virological studies, that about half of all new infections in Quebec are transmitted by people who are themselves newly infected, and are at major risk of re-transmitting the infection unknowingly. So Dr. Wainberg's team is now pursuing innovative approaches to find, test, counsel and treat high-risk groups, reducing both their risky behaviour and their infectiousness through provision of on-the spot diagnosis and interventions. Notes Dr. Wainberg, "We were the first to take this approach, but it's now been proven in five other centres."

Dr. Wainberg's work is highly influenced by the internationally acclaimed successes of his long-time colleague Julio Montaner, who is bringing treatment to BC's most vulnerable and underserved populations, and investigating whether "treatment as prevention" works to reduce the transmission of HIV. A World Health Organization research team predicts that globally, new HIV cases could be reduced by 95 per cent within 10 years if Dr. Montaner's approach could be successfully implemented world-wide.

Stephen Moses is famous for his circumcision trial, but his true leadership is in developing and providing an integrated approach to health. He works internationally with local leaders and clients to empower people to improve their own health and the health of their communities. His broader activities include research into biological and behavioural risk factors for sexually transmitted infections (STIs), including HIV, and developing interventions among vulnerable groups to reduce transmission; training health workers in how to best provide care in resource-poor settings; and developing integrated approaches to STI/HIV prevention and control.

For the future, hope lies in the development of a vaccine against HIV, a hope buoyed recently by the first tentative positive results from a vaccine trial.³⁷ Canadian contributions to this monumental challenge are coming from researchers like Ken Rosenthal and Rupert Kaul, studying mucosal immunity, very important to understanding the transmission of HIV and therefore preventing its spread. The University of Manitoba team in Kenya is identifying some of the mechanisms of natural resistance to HIV. In the meantime, other researchers like Jonathan Angel are studying immune dysfunction and testing immune-based therapies, looking for an approach that will prove effective against the ever-mutating HIV virus.

Goal 2: Slow the progression of the disease and improve quality of life

From the creation of 3TC to the international OPTIMA trial led by CTN researcher William Cameron (which compares different strategies for the management of patients who have failed first- and second-line highly active antiretroviral therapy),³⁸ Canadian researchers have consistently been at the forefront in developing new drugs and treatment strategies. Canada led the way in advocating for and proving the effectiveness of HAART, a combination of drugs that work on different aspects of the virus's replication process. One key respondent told us, "Canada is highly regarded for its ability to create and conduct these large trials."

When the combination therapies came into broad use, they were effective, but the complex regimen was hard to manage, causing significant failure rates, and debilitating side effects were common. With the critical support of the CTN, Canadian researchers have made key contributions to the large body of research that has resulted, since 2006, in most patients being able to take a single pill, once a day, with radically reduced side effects. The infrastructure underlying CTN is integrated into Canada's past achievements, as well as its hopes for future successes in treating and preventing HIV transmission.

Important clinical trials in which Canadians have participated, such as the SMART trial, which is designed to determine which of two different HIV treatment strategies results in greater overall clinical benefit,³⁹ has proven the value of early treatment: "We're not waiting until the disease manifests itself, and as a result, we're not seeing opportunistic infections." Treating people before their immune systems get too depleted has major long-term benefits, including reduced risk of dementia, much better survival rates, and better health in the added years of life.

The outstanding contributions Rafik Sekaly, Jean-Pierre Routy and their team have made to our understanding of the pathogenesis of HIV and how it may be stopped offer new possibilities for a true cure for AIDS, and not just control. A significant challenge for researchers is that a good animal model of HIV does not exist, and therefore research in human tissues is essential.

Larger cohorts are taking on increasing importance in helping improve the daily life and long-term prospects for people living with HIV/AIDS. Cohorts can follow participants for a lifetime, providing valuable information about the long-term effects of living with HIV and anti-HIV drugs, accumulating health effects like cancer incidence, and the influence of social, regional, medical and population factors. In the last ten years, investments in cohorts across Canada - in BC, Alberta, Ontario, Quebec - have formed an important national infrastructure which allows us to answer previously irresolvable clinical questions. Robert Hogg has been integral in connecting Canadian cohorts through collaborations like the Canadian Observational Cohort Collaboration (CANOC) and the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). CANOC brings together data from 50,000-60,000 patients from five cohorts across Canada, while the NA-ACCORD connects 22 cohorts across North America. These big collaborations provide research teams with access to the best research statisticians and methodologists in the world to analyze and interpret the data in ways never achievable before. With these new research methodologies, they can answer new questions. For example, this work is helping provide the data to support the increasing optimism that HAART can start much earlier.

Goal 3: Reduce the social and economic impact of HIV/AIDS

Relative to other important public-health issues, HIV/AIDS has been remarkable since its emergence for the engagement of people living with HIV in the ongoing development of treatment, policy, planning and research. The AIDS community has set new standards and expectations for how research is made relevant, who should be involved and the role different kinds of decision makers should play. As Canadian researchers more generally seek to improve health outcomes through greater integration of KT, community-based research is increasingly recognized as a key model for integrated KT. As a Key Informant noted, "It allows for more community input, control and collaboration. It's very grounded research, which translates quite directly into implementation."

In a number of populations, HIV rates are still rising. Knowledge of what AIDS is and how to protect against its transmission is widespread, and yet many people are not protecting themselves. Clearly the barrier is not lack of knowledge, but lies elsewhere in the mysteries of human behaviour and social organization. Many respondents identified preventative interventions as a major area for future investment. To be effective, such interventions need to be designed in close coordination with specific at-risk groups, so that they understand and work with the root cause of the problem. Canada's investment in community-based research will be essential in supporting the relationships and research required to tackle this currently intractable problem. Commenting on the achievements of the CBR funding stream, one of our key respondents noted, "CIHR investment has been very fruitful for starting to move the field forward. It's provided opportunities for community partners to work with policy makers to understand the complexity of the challenges and start working towards solutions. We needed to have this infrastructure in order to start doing the kind of research that can change policy. Now we have that solid foundation, strong research groups across the country, ready to go."

HIV/AIDS takes a devastating toll, both on individuals who suffer from the disease, and on the society in which they live. Canadian research is having enormous impact on reducing the costs associated with HIV/AIDS: while the drugs themselves are expensive, the costs averted by keeping an HIV-positive person fundamentally healthy can be enormous. Without effective treatment, people instead must deal with a wide range of infections and dysfunctions, all of which take their toll on the patient, their families, the health-care system and the workforce. Even more significant are the treatment costs which could be averted by reducing the transmission of HIV, such as through Dr. Montaner's treatment-as-prevention approach, which he estimates could increase the cost-effectiveness of HAART five-fold.

Goal 4: Contribute to the global effort to reduce the spread and impact of HIV

Canadian researchers have been consistently been in the vanguard of international HIV/AIDS efforts. They have been passionate – and highly successful – advocates for the development and provision of better prevention and treatment approaches and their appropriate implementation in populations with the greatest need.

Canada will continue to play a front-line role in the global HIV/AIDS effort, outweighing its financial or quantitative contributions, through the often-heroic personal efforts of the University of Manitoba teams in Kenya, our leaders in the International AIDS Society and new efforts such as the CTN-championed Canada-Africa Prevention Trial Network. Many respondents also noted the major contributions made to the global effort by Catherine Hankins, a Canadian researcher who is now the Chief Scientific Adviser to UNAIDS.

In addition, Canada is building the formal infrastructure that supports international collaboration. The CIHR-CIDA collaboration in the Canadian HIV Vaccine Initiative, which will support teams co-led by Canadian and LMIC researchers, is a promising start. As one Canadian expatriate researcher now in the US noted, "A recent IDRC [International Development Research Centre] competition, a North-South program with Canada and Africa,⁴⁰ has attracted a lot of really positive interest here. I'm afraid there's not a lot of money on the table – I don't think there's recognition of the popularity this idea would have and the potential uptake, especially among the biomedical community. There's a huge appetite – lots of Canadian biomedical people here have approached me to get connected to this opportunity."

Canadian researchers remain determined to improve the limited care and treatments provided to so much of the world's population with HIV, and continue to fight for better support, structures and opportunities. A critical need is for training that allows young people from around the world to train in top quality labs, and then take their knowledge – and adequate resources to use it – back to re-establish themselves in their home countries, while growing strong links and highly mobile interactions between emerging and established research teams. Several research leaders spoke of how well-positioned Canada was to take on leadership in this area, and the enormous value such efforts could bring Canada, in improving public health and the lives of those living with HIV, as well as in global goodwill and reputation.

Appendix: Key respondents

We thank those listed below for their invaluable assistance in identifying and explaining Canadian success stories in HIV/AIDS research. However, the authors take full responsibility for any inaccuracies of fact or interpretation that appear in text boxes 1-8.

Name	Organization
Jonathan Angel	Senior Scientist, Chronic Disease Ottawa Hospital Research Institute Professor, Faculty of Medicine University of Ottawa
Chris Archibald	Director, Surveillance and Risk Assessment Division Public Health Agency of Canada
Luis Barreto	Vice President, Public Affairs Sanofi Pasteur Ltd
Alan Bernstein	Executive Director Global HIV Vaccine Enterprise
Carl Dieffenbach	Director of AIDS Division National Institute of Allergy and Infectious Diseases National Institutes of Health
Robert Hogg	Professor, Faculty of Health Sciences Director, HIV/AIDS Drug Treatment Program BC Centre for Excellence in HIV/AIDS
Sean Hosein	Science & Medicine Editor Canadian AIDS Treatment Information Exchange (CATIE)
Charlotte Loppie Reading	Chair, Aboriginal Health Research Networks School of Public Health and Social Policy/ Centre for Aboriginal Health Research University of Victoria
Julio Montaner	Director B.C. Centre for Excellence in HIV/AIDS
Stephen Moses	Professor, Departments of Medical Microbiology, Community Health Sciences and Medicine University of Manitoba
Francis Plummer	Director General Centre for Infectious Disease Prevention and Control Public Health Agency of Canada
Christopher Power	Canada Research Chair (T1) in Neurological Infection & Immunity Departments of Medicine; Medical Microbiology & Immunology University of Alberta
Anita Rachlis	Associate Scientist Sunnybrook Health Sciences Centre
Sean Rourke	Scientific and Executive Director Ontario HIV Treatment Network Director, Research, Mental Health Service, Centre for Research on Inner City Health, St. Michael's Hospital Associate Professor, Psychiatry University of Toronto
Martin Schechter	National Director, CIHR Canadian HIV Trials Network Professor & Director, School of Population and Public Health Chair, Division of Epidemiology and Biostatistics University of British Columbia Canada Research Chair (I) HIV/AIDS & Urban Population Health
Rafik-Pierre Sekaly	Vaccine and Gene Therapy Institute Florida
Kim Thomas	Director of Programs Canadian AIDS Society
Michel Tremblay	Professor, Department of Medical Biology Canada Research Chair (T1) in Human Immuno-Retrovirology Laval University Research Center in Infectious Diseases
Mark Wainberg	Professor, Molecular Biology/ Virology Director, McGill AIDS Centre, Lady Davis Institute Jewish General Hospital
Catherine Worthington	Associate Professor Faculty of Social Work University of Calgary

References and notes

1. Canadian HIV Vaccine Initiative
2. CHVI: Consultation on CHVI Funding Programs
3. The financial data were provided by CIHR. "Other", i.e. non-HIV Initiative, spending was obtained from a keyword search. Keywords that describe a grant or award are provided at the time of application by the applicant and were validated for actual relevancy by CIHR staff. A significant proportion of the research indicated as relevant to HIV/AIDS by the applicant was not validated as such. Using the unvalidated public information in the CIHR web database, we retrieved a total investment of $366 million, compared to the validated figure of $278 million. "Indirect" funding is for projects or awards that are relevant to HIV/AIDS, but where this is not the major focus of the research. Figure 1 shows all CIHR funding, including relevant Canada Research Chairs and Networks of Centres of Excellence funding.
4. For example, in alphabetical order: ACADRE Grants of the Institute of Aboriginal Peoples' Health; Advancing Theories, Frameworks, Methods and Measurement in Health Services & Policy Grants of the Institute of Health Services and Policy Research; and Canada-HOPE Scholarships.
5. Funding Opportunity Details "Open Operating Grant".
6. Primary themes were designated by the applicants at the time funding was applied for. In those cases where no theme was designated, the theme was assigned by Mark Bisby on the basis of the title, key words or abstract of the funded project. The data shown in Figure2 exclude Canada Research Chairs and Networks of Centres of Excellence funding. HSS= Health Services and Systems.
7. Ontario Genomics Institute Viral Proteomics research project
8. Gates Foundation Funding Search Engine result
9. It does not reflect a general increase in commercialization activity nationally, since the annual number of HIV/AIDS-related patents filed, which more than doubled between 2000 and 2006, has since declined back to 2003-04 levels.
10. Funding Opportunity Details: Emerging Team Grant: HIV/AIDS Vaccine Discovery and Social Research
11. Some of the large publication databases now include a "funders" field, but we found this to be inconsistently and often inaccurately populated, and have not used it.
12. We found the same trends when we also examined the 20 most-cited papers with Canadian authors over the entire period between 2000 and mid-2009. Seven of 20 papers acknowledged direct CIHR support, but seven of the 13 that did not were sponsored by companies, or were clinical guidelines. Again, the Canadian authors of 18 of the 20 of the papers received CIHR funding; one of the non-funded authors worked in industry and was ineligible.
13. The number of new awards funded in each year depends on a number of factors: the funding allocated within the HIV Initiative; the number of applications for awards within each stream; and the quality of those applications. Figure 5 shows both new and continuing awards. Since each award may be held by the same individual over a number of years, the numbers in the columns add up to a larger number than the number of funded individuals shown in Table 1. The salary awards listed for the CBR stream are the Community-Based Research Facilitators.
14. Because this is a rather time-consuming analysis, we sampled at two-year intervals, rather than every year after 2002-03. For 2000-01, we also included those investigators who were funded through the former NHRDP (Health Canada) funding program who could be identified when their grants transferred to CIHR the following year.
15. "Investigators" refers to all principal and co-investigators listed on the grant.
16. Assuming the usual career progression of doctoral student>postdoctoral fellow>independent investigator eligible for CIHR grants, we multiply the two ratios to estimate retention of an individual. For biomedical trainees, for example, retention = (6/26) × (7/35).
17. The objective of the Doctoral Research Award is "to provide a reliable supply of highly skilled and qualified researchers" (CIHR funding opportunities database).
18. There is a lag period, typically two to four years, between the start of funding and the publication of research papers resulting from the funded work. We therefore plotted the annual number of HIV/AIDS publications with Canadian authors against funding amounts three years earlier (Figure F1), starting in 1994-95, the earliest year for which we could obtain archival data. In Figure F1 both funding and publications are plotted on a relative scale, with the first year given a value of 1. The resulting plot shows a clear positive relationship between funding level and publications, although the relationship is far from straightforward. A tripling in funding levels was associated with a doubling in the number of publications.
    Figure 1 Funding and Publication. The number of Canadian publications in HIV/AIDS are plotted against the CIHR funding three fiscal years earlier, relative to a baseline fiscal year of 1994-5
    
19. To obtain information about research productivity of Canadian investigators, we searched three major publication databases, PubMed, Web of Science (WoS) and Scopus, with a simple search string: Subject =[HIV or AIDS] AND Address/Affiliation =[Canada]. Despite the differences in the actual number of publications retrieved, the trends are consistent among the three databases.
20. In PubMed, only the address of the first (lead) author of each publication is listed. This is one reason why the number of Canadian publications retrieved from PubMed is lower. Scopus includes more of the "grey literature" than does WoS, and indexes more publications, which is why its numbers are slightly higher than WoS.
21. While 2009 data are not shown because the year's data are not yet complete, it is worth noting that, to date (November 2009), Public, Environmental and Population Health publications for 2009 exceed the number for any other year, showing that the dramatic increase in productivity is continuing.
22. 2009 data are for a partial year. Full year publications are likely to be in the range of 110 to 120. We used a number of keywords that appeared frequently in the grants funded through the CBR stream (general and aboriginal health), such as prevention, communit*, resilien*, vulnerab*, cultur*, qualitative, intervention combined with the key-words HIV and AIDS to obtain the data in Figure 11.
23. We therefore looked specifically at Canadian research output in this area, using both WoS and SCOPUS databases, and searching on the terms: subject = [HIV OR AIDS] AND [Aboriginal OR Inuit OR indigenous]. Because of the small numbers of hits, and the resulting statistical noise, in Figure 12 we have averaged the findings from the two databases. This query retrieves very few publications, from Canada or the rest of the world.
24. Using WoS data (WoS conveniently sorts hits by country of author affiliation), we can compare productivity of Canadian authors against those of other leading research nations. For this analysis we pooled data from two three-year periods to reduce the statistical fluctuations associated with small numbers of publications. We chose 1996-98, immediately prior to the establishment of the HIV Initiative, and 2006-08, representing the mature HIV Initiative.
25. In order to examine the areas in which Canadian HIV/AIDS researchers are publishing, we obtained a classification of all publications from 1996-98 and 2006-08 by discipline. Both WoS and Scopus provide this analysis automatically, but they have quite different classification schemes. The WoS scheme seemed to correspond better to CIHR's four research themes.
26. The Scopus data is generally similar, showing a decrease from 65% to 53% in the "other health" category and an increase in the proportion of social sciences publications.
27. The index of specialization is calculated as (% of Canadian publications in field x/% of world publications in field x), and in Figure 15 the index for 2006-08 publications is shown both for the disciplines in which there are most publications, and for those groupings of disciplines shown in Figure 14.
28. It is notable that Canadian papers are still the second-most-highly cited in 2006-08, because of the shift in proportion of Canadian publications away from biomedical science and towards the social-sciences disciplines over the period 1996-2008. Biomedical-science publications typically have higher citation rates than do social-science publications, and that was the case for these HIV/AIDS publications as well (see Figure 25).
29. For any given set of publications, h of them have been cited at least h times. The estimation of the h-index for 2006-08 Canadian HIV/AIDS publications is shown in Figure F2; note that only the 100 most-cited publications are plotted.
    The value of h thus depends both on how many papers originate in the country, and how often they are cited. Figure 13B shows the h-indices for the leading countries for papers published in 2006-08.
    Figure F2 Calculation of h-index for Canadian 2006-08 publications
    
30. Note that these citation rates can only be compared within columns, not across rows in Table 3. Citation rates for papers published in 2006-08 are lower than for those published in 1996-98 simply because there have been fewer subsequent citation opportunities.
31. WoS was searched using the terms "HIV or AIDS" and the years 2006-08. The results were ranked by author name frequency, and Canadian authors subsequently identified by limiting the results to those with a Canadian affiliation.
32. For example, a publication with authors from Canada, USA and France is counted once in the "USA" total, and once in the "France" total.
33. CIHR Funding Opportunity Details
34. HIV/AIDS Population Health and Health Services – Funding Decisions Notification: CIHR Funding Opportunity Summary
35. We acknowledge the assistance of Anne-Laure Grenier in conducting this survey.
36. Times Magazine: Top 10 Medical Breakthroughs, 2007
37. Supachai Rerks-Ngarm et al., "Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand." New England Journal of Medicine, published online 20 October 2009 DOI 0.1056/NEJMoa0908492
38. The OPTIMA Canadian Website
39. Canadian HIV Trials Database
40. HIV/AIDS Prevention Trials Capacity Building Grants