Canada's Report on HIV/AIDS 2003

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Advancing the Science of HIV/AIDS

Advances on the biomedical and clinical fronts, as well in various aspects of social science, are key to stopping the spread of HIV, developing better treatments and a cure for AIDS, and improving the quality of life of people living with HIV/AIDS. Canadians are at the forefront of specific areas of HIV/AIDS research and continue to expand their involvement in broad-based, collaborative research initiatives at the local, regional, national and international level.

New scientific knowledge is contributing to better responses to HIV/AIDS in Canada and worldwide, but many questions remain unanswered and new challenges continue to arise. New strains of the virus, treatment failures, widespread misconceptions and a lack of the sense of seriousness about the risks of contracting HIV/AIDS are posing new questions for biomedical and social science researchers alike.

Canadian Partners in HIV/AIDS Research

HIV/AIDS research receives a significant portion of the CSHA's annual budget - approximately $13 million per year, or 30 per cent of total CSHA spending. Most of this money is dedicated to extramural research at universities, hospitals and other institutions (see Table 2), with about $1 million being used to support epidemiological research within Health Canada. In addition, CIHR, which administers the majority of the CSHA's extramural research program, is committed to contributing at least $3.5 million per annum to HIV/AIDS research from its own budget. In 2002-2003, CIHR invested a total of $4.8 million in this work.

CIHR has begun to issue RFAs that are more strategic and targeted in order to address gaps in certain areas of research. Largely as a result of this approach, the number of new HIV/AIDS research projects approved by CIHR reached a five-year high in 2002-2003. Thirty-seven new HIV/AIDS research projects were approved by CIHR during the year, bringing the total number of projects receiving funds in 2002-03 to 89 (see Table 3).

Table 2: Federal HIV/AIDS Extramural Research Funding Streams - ($M)

	CSHA	CIHR
Community-Based Research	1
Aboriginal Community-Based Research	0.8
Biomedical/Clinical*	4.6	4.8
Health Services/Population Health*	2.4
Canadian HIV Trials Network*	3.2

*Administered by CIHR.

Table 3: CIHR-Funded Research Grants in 2002-2003

Research Program	New Projects	Ongoing Projects
Operating Grants	24	67
Randomized Controlled Trials	0	4
Group Grants	1	3
Proof of Principle	1	1
Partnership Programs	1	6
Institute Strategic Initiatives	10	8
TOTAL	37	89

Other federal funding programs also support Canadian HIV/AIDS research. For example, Genome Canada, the primary funding and information resource relating to genomics and proteomics in Canada, has invested $11.5 million over three years in large-scale research projects that will increase our understanding of the role of genetics in immune-based diseases like HIV and in opportunistic infections that pose a threat to people with weakened immune systems. The Canada Foundation for Innovation, whose mandate is to strengthen Canada's capacity to carry out world class research and development activities, also supports HIV/AIDS research infrastructure at universities and not-for-profit institutions across Canada.

The Canadian Network for Vaccines and Immunotherapeutics (CANVAC) is one of 20 networks supported by the federal Networks of Centres of Excellence Program. CANVAC, which brings together leading Canadian scientists specializing in the fields of immunology, virology and molecular biology, spent approximately $1.18 million on HIV/AIDS projects in 2002-2003.

Social Science and Community-Based Research

Canadian social science and community-based research (CBR) has contributed substantial new knowledge to HIV/AIDS prevention, care, treatment and support efforts.

For example, the aforementioned Canadian Youth, Sexual Health and HIV/AIDS Study, coordinated by CMEC, was the first national study since 1989 to focus specifically on the sexual health of adolescents. Funded by Health Canada under the CSHA and carried out by researchers at four Canadian universities (Acadia, Alberta, Laval, and Queen's), the study surveyed more than 11 000 youth in Grades 7, 9 and 11 about their knowledge, attitudes, behaviours and other factors that influence sexual health. The study results reinforce the need for a comprehensive focus on students' sexual health and the need for services directed to those most at risk of unhealthy behaviours. Among the noteworthy findings:

• Forty per cent of male students and 46 per cent of female students in Grade 11 had experienced sexual intercourse. In Grade 9, 23 per cent of male students and 19 per cent of female students had experienced sexual intercourse.
• Students in 2002 generally exhibit lower levels of sexual knowledge than those who participated in the 1989 survey. For example, two thirds of Grade 7 students and half of Grade 9 students do not know that there is no cure for HIV/AIDS.
• About half of Grade 11 students are not aware that people with sexually transmitted infections (STIs) may not have any visible symptoms.
• For the first time in Canada, the survey provides data on how young people use and perceive sexual health services and education. The findings indicate that more should be done in these areas.
• Most students report relatively rare use of harmful addictive drugs and a "happy home life," and indicate that the school serves as an important source of sexual and HIV/AIDS information.

The Canadian Youth, Sexual Health and HIV/AIDS Study will serve as a benchmark for the development and delivery of sexual health programs and initiatives for youth.

As noted earlier, in early 2003 Health Canada funded HIV/AIDS - An Attitudinal Study to determine the adult public's knowledge, awareness and behaviour with respect to HIV/AIDS and to provide direction to the Department's efforts to raise Canadians' awareness of HIV/AIDS. Among the findings:

• Nearly one in five Canadians believe HIV/AIDS can be cured if treated early.
• Although virtually all Canadians believe that HIV/AIDS is a somewhat serious or a very serious problem, an overwhelming majority of Canadians believe that their own personal risk of contracting HIV/AIDS is low.
• Forty-four per cent of Canadians do not agree that people living with HIV/AIDS should be allowed to serve the public in positions such as dentists and cooks. As well, only about 40 per cent of Canadians rate themselves as being "very comfortable" working in an office with a man or woman who developed HIV/AIDS.
• Just over one quarter of Canadians indicated that they have been tested for HIV, excluding testing for insurance purposes, blood donation and participation in research.
• When asked where they believe the federal government should be focussing its attention, half of those surveyed stated public education. One third believe the federal government should be conducting research into treatment. Canadians also believe that the federal government should be focussing attention on finding a cure/vaccine, caring for the infected and youth education and prevention.
• Nearly three quarters of Canadians support federal government involvement in HIV/AIDS. Close to two thirds of Canadians believe that the federal government should be spending more on HIV/AIDS today than it did 10 years ago, while 28 per cent believe that spending should be unchanged from 10 years ago.

Other social science research also produced important information in 2002-2003.

For example, "Positive Connections for Positive Inmates," a research project undertaken by the AIDS Calgary Awareness Association and Safeworks (Calgary Health Region), identified systemic barriers to the care, treatment and support of HIV-positive inmates in southern Alberta and made recommendations on how to improve their physical and psychosocial health.

Another study explored the social contexts within which injection drug users in Halifax use injection drug paraphernalia (either safely or not safely) and have sex (again, either safely or not safely). The study, a collaborative effort involving Dalhousie University, the Mainline Needle Exchange, the North End Community Health Centre and the Queen Elizabeth II Hospital, suggests that there is a continued need for HIV prevention measures among injection drug users in Halifax, with a particular focus on gender issues that influence unsafe practices.

The Polarias Seroconversion Study, based at the University of Toronto, is a CIHR-funded longitudinal open-cohort study of documented recent HIV-infected individuals and an HIV-negative control group in Ontario that has made numerous contributions to the field of HIV/AIDS. A key finding of this research team last year was that delayed application of condoms for anal sex is an important predictor of HIV infection among gay and bisexual men. Men who reported this practice were six times more likely to become infected with HIV.

A researcher at the King's College School of Social Work (University of Western Ontario) explored how the income level of people living with HIV/AIDS affected their access to work (both paid and volunteer), services and informal social relations. A key recommendation arising from this project was that policy and program design should focus on sources of stress, factors that affect control over stressful life events, and barriers to social engagements.

The Prisoners' HIV/AIDS Support Action Network (PASAN) undertook a qualitative study of the perceptions and experiences of female inmates living with HIV/AIDS and/or hepatitis C. Researchers interviewed 156 women in nine federal institutions across Canada to document their needs in relation to HIV/AIDS and hepatitis C prevention, care, treatment, and support, both in institutions and in the community after release. The resulting bilingual report, Unlocking Our Futures: A National Study on Women, Prisons, HIV and Hepatitis C, is a reflection of the women's voices, their needs and concerns. It identifies both gaps in service delivery and good practices, in such areas as harm reduction, prevention education, HIV testing, confidentiality, the provision of medical services, diet and nutrition, counselling, support and information. A series of recommendations are presented for CSC, Health Canada, public health departments and others to assist in the development and implementation of a "best practice" framework in this sector. For example, the study recommends that access to women-specific HIV and hepatitis C prevention education programs must be expanded and made consistent throughout the prison system. As well, female physicians should be available in all women's institutions, and inmates must have access to anonymous HIV testing.

The CSHA's investment in CBR, which generates information relevant to communities developing innovative program and policy responses to HIV/AIDS, is also beginning to produce results. For example, the Community-Based Research Network project, a three-year initiative started in 2002, serves as a repository of CBR models, tools, reports and information about ongoing studies as well as a communications medium for upcoming events. An initiative of the Community-Based Research Centre in Vancouver, the project has created a bilingual website under the guidance of a national advisory committee drawn from the Canadian HIV/AIDS CBR community, including Aboriginal representatives. A review, rating and editorial policy is being developed to enhance the quality and effectiveness of the website.

CAAN is working on several CBR projects under the Aboriginal Community-Based Research Program. These include studies entitled Canadian Aboriginal People Living with HIV/AIDS: Care, Treatment and Support Issues (Praxis Research Associates); Joining the Circle, Phase II: Aboriginal Harm Reduction (Sir Wilfred Laurier University); and Addressing Homophobia in Relation to HIV/AIDS in Aboriginal Communities (University of Manitoba).

Clinical Trials Test HIV/AIDS Treatment Options

The CTN - the principal organization conducting HIV/AIDS clinical trials in Canada - is a partnership of researchers and research institutes committed to developing treatments, vaccines and a cure for HIV/AIDS. Through CIHR, the CTN receives $3.2 million in CSHA funding each year to work with clinical investigators, people living with HIV/AIDS, the pharmaceutical industry, physicians, specialists and laboratories to assess experimental HIV/AIDS therapies. Many CTN trials have also been successful in obtaining additional support directly from CIHR, which has enabled the CTN to move away from industry-sponsored trials to investigator-initiated, peer-reviewed trials.

The CTN underwent a CIHR-administered peer review process by an international panel of experts in 2002-2003. The international reviewers gave the CTN an excellent rating and praised the Network as a useful and productive investment of CSHA dollars. As a result of this review, the CTN was awarded a grant for another five-year term, with an increased budget to support its activities beginning in 2003-2004.

In 2002-2003, the CTN facilitated 16 HIV clinical trials - five of them new - involving more than 800 Canadians with HIV/AIDS. The CTN also reviewed 13 new trial protocols and approved five. CTN trials that published results in 2002-2003 include:

• CTN 102, the Nelfinavir vs. Ritonavir Study, which showed that the antiviral activity of either nelfinavir or ritonavir as part of highly active antiretroviral therapy (HAART) was similar and resulted in a substantial decline in disease progression over nearly four years of follow-up. The study also showed that nelfinavir was better tolerated than ritonavir. This equivalence, open-label study, which enrolled 253 participants across Canada, was the first large-scale trial in which the CTN collaborated with a U.S.-based trials network and the first to compare the clinical efficacy of nelfinavir to ritonavir when added to background therapy.
• CTN 160, the Double Non-Nucleoside Study, which evaluated the antiviral efficacy and safety of nevirapine and efavirenz - the two most widely used non-nucleoside reverse transcriptase inhibitors - in combination therapy with 3TC and d4T. The study concluded that treatment failure was similar in the efavirenz and the nevirapine arms but was highest in the nevirapine plus efavirenz arm, mainly due to more treatment discontinuations in this arm. This study suggests that nevirapine once daily or twice daily is a reasonable alternative to efavirenz. Dual non-nucleoside treatment appears to offer no advantage.

CTN researchers have also determined that treatment for HIV infection may start later than originally believed without compromising the medical outcome for the individual being treated. Treatment traditionally began when the patient reached a CD4 count of 500, but new evidence indicates that treatment can be delayed until the CD4 count is 200. This can benefit patients (by delaying the potentially harmful side effects of HIV therapies) and translate into health care savings.

Clinical research is ongoing in many areas. For example, CTN researchers are conducting a clinical trial to determine if a structured treatment interruption, also known as a "planned drug holiday," is beneficial before switching to a new regimen. Structured treatment interruption is a new investigational approach to managing HIV-infected patients who are experiencing treatment failure. Approximately 200 HIV-infected volunteers across Canada will participate in the trial (CTN 164), which will assess the risks and benefits of structured treatment interruption in terms of viral response, CD4-count response, safety, quality of life and other factors.

Advancements in Biomedical Research

Biomedical research continues to produce information that is essential to understanding the virus and to developing effective strategies to treat HIV/AIDS and opportunistic infections.

CIHR-funded researchers at the University of Western Ontario and Robarts Research Institute have been focussing their efforts on understanding the side effects of drugs in HIV-infected patients. The researchers have identified that the side effects may be due to changes in patients' cells as a result of virus-produced proteins, which change some key elements of cellular function. These changes have included a reduction in the production of glutathione (a key defence against stress in the cell) related to production of a specific HIV protein. These reductions make the cells much more vulnerable to drug break-down products, and cellular injury and death can then produce serious side effects during treatment. Research continues into how these cellular changes occur in order to develop strategies to reduce the number and severity of drug side effects among people with HIV and AIDS.

Researchers from the University of Western Ontario, in collaboration with colleagues at the Hospital for Sick Children in Toronto, have also been investigating the treatment of HIV in children. The team has demonstrated that children living with HIV experience problems with the palatability of a large number of antiviral drugs and that the side effects of many drugs used in the treatment of HIV appear to be different among children with HIV than among adults.

Another important aspect of the treatment of HIV infection is the poor response to antiviral therapy and the emergence of resistant strains of the virus in the central nervous system. Researchers at the University of Toronto have been investigating the properties of various antiviral drugs in relation to the emergence of resistant strains of HIV-1 in the brain. Their results have revealed important information on the transport of drugs within the central nervous system. Knowledge of the mechanisms that regulate drug delivery in the brain will assist with the development of novel pharmacological treatment approaches and prevention of HIV-1-induced injury to the nervous system.

Opportunistic infections occur in HIV-infected people as a result of a weakened immune system. Mucosal candidiasis is a common and debilitating fungal infection in HIV patients that is being studied by researchers at Sainte-Justine Hospital, University of Montréal and the Clinical Research Institute of Montreal. The work of this team, performed using transgenic mice reproduce the features of candidiasis in human HIV infection, has revealed the specific cell types that are involved in susceptibility to mucosal candidiasis (Langerhans cells, CD4+ T-cells, CD8+ T-cells). Their studies provide new insights into the alterations of host defence mechanisms in HIV-infected patients that predispose them to mucosal candidiasis. This new knowledge is an essential prerequisite to rational, targeted augmentation of defective immune cell populations in HIV-infection.

Improving HIV/AIDS Testing Methodologies

HIV testing technologies support research and improve our understanding of new HIV strains and issues such as drug resistance.

In 2002-2003, CIDPC initiated a project with the National Institutes of Health and Centers for Disease Control in the United States to investigate low-cost diagnostic and prognostic tests for HIV. Specifically, researchers are developing a test that would reduce reagent use by about 40 per cent. (When added to a substance, reagents cause a reaction that aids in determining the composition of the substance). At the same time, reagent manufacturers are being asked to reduce their prices in resource-poor settings. Currently, a CD4 count test costs about C$50 to administer, including the cost of equipment. Canadian and U.S. researchers are endeavouring to reduce this cost to about C$25 for industrialized nations and C$3 for resource-poor settings.

CIDPC has also begun to develop and implement drug resistance quality assurance programs in collaboration with the British Columbia Centre for Excellence in HIV/AIDS. These programs are designed to ensure that drug resistance monitoring is equivalent across Canada in terms of testing, interpretation of the results and standardization of care. Canada is seen as a world leader in drug resistance surveillance, and this project has attracted the participation of a number of other countries.

New Epidemiology Estimates Point to A Need for Greater Vigilance

New national HIV prevalence and incidence estimates released by Health Canada in the fall of 2003 indicate that rates of HIV infection are still unacceptably high among all exposure categories. Greater vigilance is required to turn the corner on Canada's HIV/AIDS epidemic.

The new estimates reveal that more people are living with HIV infection (prevalent infection) in Canada than ever before. At the end of 2002, an estimated 56 000 people in Canada were living with HIV infection (some of whom also had AIDS), an increase of 12 per cent compared with the end of 1999 when an estimated 49 800 people were HIV-positive. In terms of exposure categories among the 2002 prevalent infections, 32 500 were MSM (accounting for 58 per cent of the total), 11 000 were injection drug users (20 per cent of the total), 10 000 were heterosexuals (18 per cent of the total), 2 200 were MSM/injection drug users (four per cent of the total) and 300 infections (less than one per cent of the total) were attributed to other types of exposure. Of particular concern is the fact that about 30 per cent of HIV-infected people at the end of 2002 (an estimated 17 000 individuals) were unaware of their HIV infection. These individuals are "hidden" to the health care and disease-monitoring systems since they have not yet been tested and diagnosed for HIV infection.

The number of new HIV infections (incident infections) continues at approximately the same rate as three years ago. In Canada, there were an estimated 2 800 to 5 200 new HIV infections in 2002, compared with the estimate of 3 310 to 5 150 new infections in 1999. MSM continue to comprise the greatest number of new infections, accounting for 40 per cent of the national total, which is a slight increase from 38 per cent in 1999. The proportion of new infections among injection drug users has decreased slightly, from 34 per cent of the total in 1999 to 30 per cent in 2002, while the proportion attributed to the heterosexual exposure category increased slightly, from 21 per cent in 1999 to 24 per cent in 2002. (Figure 1 provides a comparison of the distribution of new infections among different exposure categories from 1981 to the end of 2002.)

Among the other significant trends noted in the data:

• At the end of 2002, an estimated 7 700 women were living with HIV in Canada, (including those living with AIDS), accounting for about 14 per cent of the national total. This represents a 13 per cent increase from 1999. The number of new infections among women attributed to the heterosexual category increased from 46 per cent in 1999 to 53 per cent in 2002, with the remainder of new infections among women attributed to IDU.
• An estimated 3 000 to 4 000 Aboriginal people in Canada were living with HIV at the end of 2002, accounting for five to eight per cent of the national total (Aboriginal people accounted for about six per cent of the estimated prevalent infections in 1999). The composition of exposure categories among Aboriginal people did not change significantly between 1999 and 2002. (The distribution in 2002 was 63 per cent attributed to IDU,
• 18 per cent heterosexual, 12 per cent MSM and seven per cent MSM-injection drug users).
• An estimated 3 700 to 5 700 people who were born in countries where HIV is endemic were living with HIV at the end of 2002, accounting for seven to 10 per cent of the national total.

The new estimates confirm that concerted action is required to prevent new infections among all risk groups and to provide services for the increasing number of Canadians living with HIV infection.

Vaccine and Microbicide Development Continues

CIDA invested $15 million in vaccine research in 2002-2003 as part of a three-year, $45 million commitment to IAVI announced at the G8 Summit in Kananaskis, Alberta, in June 2002. This contribution makes Canada the largest government donor to IAVI. Canada is also contributing $5 million to the African AIDS Vaccine Programme, for a total commitment to international vaccine development of $50 million over three years.

Clinical trials of AIDSVAX were concluded in 2002-2003. CTN researchers were involved in the trials, which took place in North America, the Netherlands and Thailand. Although this international initiative did not achieve the hoped-for results, it was an important learning experience for the CTN (this was only the second time the Network actively participated in a vaccine trial) and others around the world.

On the domestic front, CIDPC is collaborating with industry and academic researchers on pre-clinical evaluations of the efficacy of new HIV vaccines. These evaluations are required before clinical trials can begin. Two projects are under way: one involving the University of Ottawa, the National Research Council of Canada and a biotechnology company (owner of the intellectual property) and another in partnership with McMaster University, McGill University and the University of Toronto.

In October 2003, a one-day symposium was held in Ottawa to identify how Canadian researchers, biotechnology companies, ASOs and development NGOs can promote the research and development of microbicides. The symposium was cosponsored by ICAD, Health Canada, CIHR, CIDA, the International Partnership for Microbicides, the Microbicide Advocacy Group Network (MAG-net; coordinated by CAS) and the Global Campaign for Microbicides.

Figure 1: Estimated exposure category distributions (%) among new HIV infections in Canada, by time period.

MSM: men who have sex with men; IDU: Injecting drug users; Heterosexual: sub-categories of heterosexual contact with a person at risk for HIV, origin in a country where HIV is endemic and heterosexual as the only identified risk

Challenges and Opportunities

Through research efforts in Canada and internationally, our understanding of the science of HIV/AIDS continues to improve. Advances are being made on the biomedical, clinical and social science fronts, and community-based research is becoming more robust. With each step forward, however, new challenges emerge in the form of drug-resistant HIV strains, treatment failures and the need for new, more effective interventions to prevent infection in at-risk populations.

Achieving true advances in health research is resource-intensive. CSHA partners continue to cite the need for increased funding to carry out HIV/AIDS research, upgrade the research infrastructure and attract and retain qualified scientists and support staff. Communication could also be enhanced within the research community and between researchers and other stakeholders. As well, epidemiological research in Canada needs to be strengthened in order to provide information that will improve estimates of HIV incidence and prevalence. The increased cost of insurance for research projects, the complexity of research contracts (for example, for clinical trials) and the need for better information to monitor the epidemic have also been identified as challenges for Canada's HIV/AIDS research community.

Jenny Saarinen: Making A Difference in South Africa

Jenny Saarinen's introduction to the HIV/AIDS epidemic in South Africa was harsh but effective. The day after arriving on a six-month internship sponsored by the Interagency Coalition on AIDS and Development and funded by the Canadian International Development Agency, Ms. Saarinen was taken to the hospital in Eshowe, a small rural community in KwaZulu-Natal province, where an entire ward is set aside for HIV/AIDS patients. She watched helplessly as a patient died, and the next day attended the funeral.

"I was quite shocked to see a ward full of people who were obviously very sick," she recalls of her first hospital visit. "But it was a good way to be introduced to the place and the problem. I saw pretty quickly that it was an issue that was invading the whole community on many levels."

An Alberta native who is currently completing a master's degree in international social work at the University of Calgary, Ms. Saarinen was in Eshowe to work with the Tugela AIDS Program (TAP). TAP is one of only a handful of AIDS service organizations in the remote northern region of the province and is experiencing financial difficulties due to cutbacks by the provincial department of health.

Against this backdrop, Ms. Saarinen's primary task was to help ensure the long-term sustainability of TAP by developing fund-raising materials that will enable the organization to attract financial assistance from domestic and international donors. However, she also worked closely with TAP's director of training to deliver peer education workshops to youth, farm and mill workers and traditional leaders throughout northern KwaZulu-Natal province. It was on these travels that she saw the most difficult aspects of life in South Africa but also enjoyed her most rewarding experiences.

"I think the workshops I helped deliver were the greatest achievement of my internship. I was connecting with people and had several really wonderful one-on-one experiences in the workshops and afterward. I felt I was doing something concrete and that we were learning together."

Ms. Saarinen has other lasting impressions from her time in South Africa. "HIV/AIDS was everywhere. One day, in a 40-minute period, I counted six or seven public service announcements about HIV/AIDS on the radio. Every billboard in my township was an AIDS awareness billboard. But a lot of people still didn't want to talk about HIV/AIDS."

Overall, Ms. Saarinen received a tremendously positive and warm welcome from the people of Eshowe and the surrounding area. "People were both amazed and happy that I was there," she remembers. "I was the only white person in King Dinizulu township." At the same time, she struggled to come to grips with gender relationships in rural South Africa, which are dramatically different than in Canada.

"I'm still trying to figure out how I feel about what I saw, the way men and women interacted. In some situations, I could feel power being taken away from me because of my gender. I understand there is a different cultural context, but it was still very difficult."

Ms. Saarinen is using the knowledge and experience she gained in South Africa to inform others about the epidemic. Since returning to Canada, she has made presentations at an AIDS conference in Ontario and to groups ranging from AIDS Calgary to the United Church. She is also doing research on HIV/AIDS in Alberta for a professor at the University of Calgary, and is looking forward to comparing what she learns from this work to her experiences in South Africa.

As for the future, Jenny Saarinen's career path remains open. "I guess I have always imagined I would go back to Africa if the opportunity arose," she acknowledges. "HIV/AIDS remains a big interest for me."

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