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To provide an overview of the epidemiologic parameters of emerging adverse effects associated with antiretroviral therapy for human immunodeficiency virus (HIV) disease. All available antiretroviral agents are associated with significant adverse drug effects. Of particular interest are newly emerging suspected adverse drug effects which were not generally noted in pre-marketing trials nor captured under current standard clinical care practices. Suspected antiretroviral toxicities meeting these criteria include: HIV-associated lipodystrophy which can include peripheral lipoatrophy, lipohypertrophy and metabolic abnormalities; hyperlactatemia and lactic acidosis; and metabolic bone abnormalities such as decreased bone mineral density, osteoporosis and osteonecrosis. Results of prospective and observational studies reported to date suggest that these abnormalities, while aetiologically complex, are likely attributable to treatment factors and may be intricately interrelated. The medical management of these symptoms remains unsatisfactory given the unexplored efficacy of traditional approaches in the HIV positive population. While the pathogenic mechanism of these disorders remains obscure, a theory of tissue-specific mitochondrial toxicity has been proposed. With the continued introduction of novel therapies and standard treatment with combination therapy, new adverse events will continue to emerge among persons being treated for HIV disease. Beyond their immediate clinical implications, these events may contribute to changing patterns of antiretroviral utilisation including therapy initiation, adherence and cessation.

The Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort is a census of all identified HIV-positive individuals in the province of British Columbia. It was formed through the linkage of nine provincial treatment, surveillance and administrative databases. This open cohort allows for bidirectional analyses from 1996 onward and is refreshed annually. Extensive data collection for cohort members includes demographic information, detailed clinical and laboratory data, complete prescription drug use including antiretroviral agents, and information on health service utilization encompassing inpatient and outpatient care, addictions treatment and palliative care. This cohort provides an unprecedented opportunity to evaluate, over an extended time period, patterns and determinants of key outcomes including engagement in the cascade of HIV care from diagnosis to treatment to viral suppression as well as monitoring trends in medical costs, health outcomes and other key healthcare delivery indicators at a population level with wide-ranging, high-quality data. The overall purpose of these activities is to enable the development and implementation of strategically targeted interventions to improve access to testing, care and treatment for all HIV-positive individuals living in British Columbia. As a programme of the Ministry of Health, the STOP HIV/AIDS Evaluation Evaluation Team welcomes input from all stakeholders and possible partners via contact with the Director of Operations for the British Columbia Centre for excellence in HIV AIDS, Ms. Irene Day (iday@cfenet.ubc.ca).

Objective To provide population-based estimates of the prevalence of lipodystrophy syndrome and constituent symptoms and to identify correlates of prevalent symptomology. Methods Participants in a province-wide HIV/AIDS treatment programme reported morphological and metabolic abnormalities. Probable lipodystrophy was defined as self-report of at least one morphological abnormality or both high cholesterol and triglyceride levels. Explanatory variables investigated included: age; sex; ethnicity; transmission risk group; CD4 cell count; plasma viral load; AIDS diagnosis; duration of infection; alternative therapy use; past, current and duration of use of antiretroviral therapy (ART) by class and specific drug; total duration of ART; and current adherence. Stepwise logistic regression identified possible determinates of lipodystrophy. Results Of 1035 participants, 50% appeared to have probable lipodystrophy, with 36% reporting peripheral wasting, 33% abdominal weight gain, 6% buffalo hump, and 10 and 12% increased triglyceride or cholesterol levels, respectively. In multivariate analysis, lipodystrophy was associated with older age (per year) (AOR 1.03; 95% CI 1.01, 1.04), the use of ingested alternative therapies (AOR 1.46; 95% CI 1.06, 2.01), having ever used protease inhibitors (PI) (AOR 2.63; 95% CI 1.89, 3.66), and duration of stavudine treatment (per year) (AOR 1.35; 95% CI 1.15, 1.58). In analysis limited to participants exposed to PI, after similar adjustment, the duration of lamivudine rather than stavudine treatment was associated with lipodystrophy (AOR 1.32; 95% CI 1.13, 1.53). Conclusion Increased risk of abnormalities is associated with the use of PI, and the duration of stavudine and lamivudine treatment after adjustment for personal characteristics, clinical disease stage, duration of infection and detailed treatment history.

Objective : To assess the impact of HIV infection and AIDS on mortality patterns in Canada with specific reference to gender and regional differentials and to other leading causes of death. Design : Descriptive, population-based study. Setting : Canada. Patients : All persons for whom HIV/AIDS [ninth revision of the International Classification of Diseases (ICD-9) 042-044] was recorded as the underlying cause of death as reported to Statistics Canada between 1987 and 1992. For comparative purposes data was obtained on five other leading underlying causes of death including coronary heart disease (ICD-9 410-414), motor vehicle accidents (ICD-9 E810-E819), and suicides (ICD-9 E950-E959) in men and women, lung cancer (ICD-9 162) in men and breast cancer (ICD-9 174) in women. Population figures were obtained from Statistics Canada estimates. Main outcome measures : Age and cause-specific mortality rates, standardized mortality ratios (SMR), potential years of life lost (PYLL) before age 65 years, and life expectancy lost due to a select underlying cause of death. Results : Over the period 1 January 1987 to 31 December 1992, 5546 deaths attributed to HIV/AIDS (5229 in men and 317 in women) were recorded in Canada. SMR for men were significantly higher than the national average in the cities of Vancouver, Toronto and Montreal, whereas those for women were significantly greater only in Montreal. Deaths from HIV/AIDS accounted for 3.6% of PYLL in men and 0.4% of PYLL in women. In 1992, HIV/AIDS was the third leading cause of male PYLL surpassing lung cancer. In the cities of Montreal, Toronto, and Vancouver HIV/AIDS was the leading cause of PYLL and was responsible for significant decrease in life expectancy at birth in men over the study period. Conclusions : HIV/AIDS has had considerable impact on mortality within Canada, principally among men and particularly in the cities of Toronto, Vancouver and Montreal.

To determine the knowledge of HIV-disease management and the adherence to contemporary guidelines among British Columbia physicians whose practices focused on HIV/AIDS.Self-administered mail survey.All 659 physicians registered in a province-wide HIV/AIDS drug treatment program.Data on demographic and personal characteristics of respondents, level of HIV-related experience, use of preventive vaccinations and tests, and preferred approaches to the prophylaxis and treatment of common opportunistic infections. Knowledge scores in 4 areas of patient care, as well as an overall score, were computed by comparing respondents' answers with the therapeutic strategies recommended at the time of the survey. Associations between physician characteristics and knowledge scores were identified by linear regression analysis.Of the 659 physicians surveyed, 65% returned responses: only 38% returned completed surveys while a further 27% returned a follow-up survey that asked nonrespondents about their demographic characteristics and HIV-related experience. Scores for specific areas of patient management ranged from 29% for the treatment of opportunistic infections to 62% for preventive measures, with a mean overall score of 47%. Physician knowledge in all areas of patient care was associated with the number of HIV-positive patients in the practice (p = 0.003 to p0.001). Physicians who were younger were more knowledgeable regarding preventive measures (p = 0.001); those whose practice location was in Vancouver had a greater knowledge of prophylaxis (p = 0.047); and those who had medical specialty training were more knowledgeable about the treatment of opportunistic infections (p = 0.009).There is substantial disparity in how physicians approach the management of HIV and related conditions. Deviations from therapeutic guidelines are common and may be associated with physician characteristics, particularly lack of experience in managing HIV.

To characterize migration patterns of persons with AIDS in Canada during the period from AIDS diagnosis to death.Descriptive, population-based study.Canada.Canada's AIDS Case Reporting Surveillance System (ACRSS) was linked to deaths in the Canadian Mortality Data Base (CMDB). Probabilistic linkage was based on initials, date of birth, date of death, birthplace, and location at diagnosis and at death. Analysis was restricted to AIDS cases reported from Jan. 1, 1982, to Sept. 30, 1994, and to deaths reported from Jan. 1, 1982, to Dec. 31, 1992.Change in usual place of residence; migration rates by region and community size.A total of 5755 AIDS cases recorded in the ACRSS were linked to deaths in the CMDB. Of these linked cases, 5366 (93%) included information on province or territory of usual residence or community size. A total of 160 (3.0%) persons with AIDS changed their province or territory of residence between the time of their AIDS diagnosis and death. Multivariate analysis indicated that those who changed residences between AIDS index diagnosis and death were more likely than other persons with AIDS to live in provinces other than British Columbia, Ontario and Quebec (p0.001), to be diagnosed earlier (p = 0.004), to be younger (p0.001) and to be gay or bisexual (p = 0.042).Our analysis revealed that only a small proportion of persons changed their residence between AIDS diagnosis and death. Geographic mobility was the greatest among persons with AIDS residing outside of the regions where the overwhelming majority of persons with AIDS in this country reside.

The aims of this study were to assess the degree of heterogeneity in the knowledge of therapeutic management of HIV infection among HIV-experienced physicians in British Columbia, Canada, and to identify associations between physician characteristics and their agreement with contemporary therapeutic guidelines. A self-administered anonymous questionnaire was mailed to 6500 physician members of the British Columbia Medical Association. The questionnaire provided information about demographic and personal characteristics, including sex, age, medical specialization and practice location; level of experience in treating HIV-infected patients; use of HIV testing procedures; use of preventative vaccinations and tests; and preferred approaches to antiretroviral therapy and the prophylaxis and acute treatment of opportunistic infections. We compared physicians' patterns of knowledge with contemporary recommendations. Logistic regression identified associations between physician characteristics and their agreement with contemporary guidelines. A total of 463 HIV-experienced physicians (a high proportion of the HIV-experienced physicians in British Columbia, Canada) responded to the questionnaire. The agreement with contemporary guidelines about HIV testing and preventative vaccinations and tests among responders ranged from 27% to 71%. For antiretroviral therapy, agreement with the guidelines ranged from 12% to 35%. For the prophylaxis and treatment of opportunistic infections, agreement with the guidelines ranged from 11% to 89% (prophylaxis) and from 46% to 91% (treatment). Regression analysis revealed that physicians actively involved in the care of HIV-infected patients were more likely to agree with the guidelines in all areas of patient care. General practitioners were more likely to agree with the guidelines regarding preventative therapies, and male general practitioners under 45 years old were more likely to agree with the guidelines on antiretroviral therapy. Our data confirm that there is substantial heterogeneity in the management of HIV-associated disease, including some deviations from contemporary guidelines. Concordance with contemporary guidelines increased with the physician's level of HIV-related experience. Our results support the idea that adherence to state-of-the-art practices may be responsible, at least in part, for the recently described association between physician experience and improved survival of HIV-infected individuals.

To assess the impact of HIV infection and AIDS on mortality patterns in Canada with specific reference to gender and regional differentials and to other leading causes of death.Descriptive, population-based study.Canada.All persons for whom HIV/AIDS [ninth revision of the International Classification of Diseases (ICD-9) 042-044] was recorded as the underlying cause of death as reported to Statistics Canada between 1987 and 1992. For comparative purposes data was obtained on five other leading underlying causes of death including coronary heart disease (ICD-9 410-414), motor vehicle accidents (ICD-9 E810-E819), and suicides (ICD-9 E950-E959) in men and women, lung cancer (ICD-9 162) in men and breast cancer (ICD-9 174) in women. Population figures were obtained from Statistics Canada estimates.Age and cause-specific mortality rates, standardized mortality ratios (SMR), potential years of life lost (PYLL) before age 65 years, and life expectancy lost due to a select underlying cause of death.Over the period 1 January 1987 to 31 December 1992, 5546 deaths attributed to HIV/AIDS (5229 in men and 317 in women) were recorded in Canada. SMR for men were significantly higher than the national average in the cities of Vancouver, Toronto and Montreal, whereas those for women were significantly greater only in Montreal. Deaths from HIV/AIDS accounted for 3.6% of PYLL in men and 0.4% of PYLL in women. In 1992, HIV/AIDS was the third leading cause of male PYLL surpassing lung cancer. In the cities of Montreal, Toronto, and Vancouver HIV/AIDS was the leading cause of PYLL and was responsible for significant decrease in life expectancy at birth in men over the study period.HIV/AIDS has had considerable impact on mortality within Canada, principally among men and particularly in the cities of Toronto, Vancouver and Montreal.

BACKGROUND In light of accumulated scientific evidence of the secondary preventive benefits of antiretroviral therapy, a growing number of jurisdictions worldwide have formally started to implement HIV Treatment as Prevention (TasP) programs. To date, no gold standard for TasP program monitoring has been described. Here, we describe the design and methods applied to TasP program process monitoring in British Columbia (BC), Canada. METHODS Monitoring indicators were selected through a collaborative and iterative process by an interdisciplinary team including representatives from all 5 regional health authorities, the BC Centre for Disease Control (BCCDC), and the BC Centre for Excellence in HIV/AIDS (BC-CfE). An initial set of 36 proposed indicators were considered for inclusion. These were ranked on the basis of 8 criteria: data quality, validity, scientific evidence, informative power of the indicator, feasibility, confidentiality, accuracy, and administrative requirement. The consolidated list of indicators was included in the final monitoring report, which was executed using linked population-level data. RESULTS A total of 13 monitoring indicators were included in the BC TasP Monitoring Report. Where appropriate, indicators were stratified by subgroups of interest, including HIV risk group and demographic characteristics. Six Monitoring Reports are generated quarterly: 1 for each of the regional health authorities and a consolidated provincial report. CONCLUSIONS We have developed a comprehensive TasP process monitoring strategy using evidence-based HIV indicators derived from linked population-level data. Standardized longitudinal monitoring of TasP program initiatives is essential to optimize individual and public health outcomes and to enhance program efficiencies.