Katherine Heath

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.

Objective To identify patient and physician characteristics that may act as determinants of adherence to prescription refill of triple combination antiretroviral therapy. Methods A population-based analysis of antiretroviral therapy-naive HIV-positive men and women in British Columbia, Canada, who initiated triple combination therapy between August 1 1996 and October 31 1998. Study participants were considered adherent if they were actually dispensed antiretrovirals ≥95% over the first year of therapy. Log-binomial regression was used to identify patient and physician characteristics associated with adherence to prescription refill. Results Of the 886 individuals eligible for analysis, 495 (56%) were ≥95% adherent to prescription refill. In multivariate analysis, adherence was positively associated with increased age [adjusted relative rate (ARR) 1.19; 95% CI: 1.07–1.32], having a diagnosis of AIDS (ARR 1.66; 95% CI: 1.29–2.15), being male (ARR 1.79; 95% CI: 1.27–2.53), and with gre...

Because of established links between entrenched poverty and risk of HIV infection, there have long been warnings that HIV/AIDS will disproportionately affect Aboriginal people in Canada. We compared HIV incidence rates among Aboriginal and non-Aboriginal injection drug users (IDUs) in Vancouver and studied factors associated with HIV seroconversion among Aboriginal participants. This analysis was based on 941 participants (230 Aboriginal people) recruited between May 1996 and December 2000 who were seronegative at enrollment and had completed at least one follow-up visit. Incidence rates were calculated using the Kaplan-Meier method. The Cox proportional hazards regression model was used to identify independent predictors of time to HIV seroconversion among female and male Aboriginal IDUs. As of May 31, 2001, seroconversion had occurred in 112 (11.9%) of the participants, yielding a cumulative incidence of HIV infection at 42 months of 12.7% (95% confidence interval [CI] 10.3%-15.1%...

We aimed to characterize changes in patterns of new HIV diagnoses, HIV-related mortality, and HAART use in Canada from 1995 to 2008. Data on new HIV diagnoses were obtained from Health Canada, HIV-related mortality statistics were obtained from Statistics Canada, and information on the number of people on HAART was obtained from the single antiretroviral distribution site in British Columbia (BC), and the Intercontinental Marketing Services Health for Ontario and Quebec. Trends of new HIV-positive tests were assessed using Spearman rank correlations and the association between the number of individuals on HAART and new HIV diagnoses were estimated using generalized estimating equations (GEE). A total of 34,502 new HIV diagnoses were observed. Rates of death in BC are higher than those in Ontario and Quebec with the rate being 2.03 versus 1.06 and 1.21 per 100,000 population, respectively. The number of HIV infected individuals on HAART increased from 5,091 in 1996 to 20,481 in 2008 ...

The objective of this study is to determine the opinions of a random sample of Canadian family physicians and a population of non-specialist physicians known to provide care to persons with HIV/AIDS about the legalization of physician assisted suicide for persons with HIV disease. In addition, we have attempted to ascertain the physician characteristics that may be associated with a favourable or negative opinion. Self-administered, anonymous questionnaires were mailed to 2,890 family physicians across Canada. Logistic regression analysis was used to determine whether physician characteristics were predictive of agreement with the legalization of physician assisted suicide. Of the respondents who had an opinion, 60% agreed with the legalization of physician assisted suicide. Multivariate analyses indicated that physicians who were living in the provinces of British Columbia (BC), Ontario, or Québec (OR = 1.63, 95% CI: 1.10, 2.43) and who provided routine follow-up care (OR = 1.85, 95% CI: 1.30, 2.63) or palliative care (OR 1.66, 95% CI: 1.13, 2.44) to those with HIV disease were more likely to agree with legalization of physician assisted suicide. This analysis demonstrates a strong support for the legalization of physician assisted suicide for persons with HIV disease among physicians experienced in providing care to those affected.

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.

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. 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 in...

In the HPTN 052 trial, antiretroviral treatment (ART) lowered the risk of HIV transmission by 96% in sero-discordant couples [1]. Increased ART coverage has also been associated with lower rates of HIV transmission at the community level [2]. The aims of this study were (1) to investigate the relationship between the percentage of HIV infected individuals on ART and HIV incidence in a multi-country analysis; (2) To compare ART coverage rates between low, middle and high-income countries.

Objective In 2014, UNAIDS and partners set the 90-90-90 targets for the HIV treatment cascade. Multiple social, political and structural factors might influence progress towards these targets. We assessed how close countries and regions are to reaching these targets, and compared cascade outcomes with HIV prevalence, gross domestic product (GDP)/capita, conflict and corruption. Methods Country-level HIV cascade data on diagnosis, ART coverage and viral suppression, from 2010 to 2016 were extracted from national reports, published papers and the www.AIDSinfoOnline database, and analysed. Weighted least-squares regression was used to assess predictors of cascade achievement: region, HIV prevalence, GDP/capita, the 2016 Corruption Perceptions Index (CPI), which is an international ranking system, and the 2016 Global Peace Index (GPI), which ranks all countries based on three main categories: societal safety, militarisation and conflict. Results Data were available for diagnosis for 84 ...

 Achievement of a sustained virologic response (SVR) after treatment for Hepatitis C infection is associated with improved outcomes. This meta-analysis aimed to determine the impact of SVR on long-term mortality risk compared with non-responders in a range of populations.  An electronic search identified all studies assessing all-cause mortality in SVR and non-SVR patients. Eligible articles were stratified into general, cirrhotic, and HIV co-infected populations. The adjusted hazard ratio (95%CI) for mortality in patients achieving SVR versus non-SVR, and pooled estimates for the five-year mortality in each group were calculated.  31 studies (n=33,360) were identified as suitable for inclusion. Median follow-up time was 5.4 years (IQR 4.9-7.5) across all studies. The adjusted hazard ratio of mortality for patients achieving SVR versus non-SVR was 0.50 (95%CI 0.37-0.67) in the general population, 0.26 (95%CI 0.18-0.74) in the cirrhotic group, and 0.21 (0.10-0.45) in the co-infected ...

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 p < 0.001). 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.

A patient's coronary heart disease (CHD) risk must be correctly classified to successfully apply risk-based guidelines for treatment of hypercholesterolemia. To determine the classification accuracy of the National Cholesterol Education Program (NCEP) CHD risk-stratification system and compare it with a simple revised system that gives greater weight to age as a CHD risk factor. Modeling of 10-year CHD risk, using equations from the Framingham Heart Study applied to a cross-sectional survey of the US population. The 3284 subjects aged 20 to 74 years surveyed in the Second National Health and Nutrition Examination Survey (1978-1982) who had fasting lipid levels measured. The area under the receiver operating characteristic curve (AUC) for 10-year CHD risk for the NCEP and revised scales. Among all adults with a low-density lipoprotein cholesterol value of at least 4.1 mmol/L (160 mg/dL), the NCEP system showed fairly good discrimination (AUC=0.90), though there was a substantial decline among men 35 to 74 years old and women 55 to 74 years old (AUC=0.81). By contrast, the revised system showed superior performance in all hypercholesterolemic adults (AUC=0.94-0.97) as well as in the subgroup of men 35 to 74 years old and women 55 to 74 years old (AUC=0.94-0.96). Simple modifications of the NCEP treatment criteria result in a substantially improved ability to discriminate between higher and lower CHD risk groups. Unlike the NCEP system, this revised system retains its classification ability in all age groups studied.

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.

Clinical trials have established the efficacy of antiretroviral therapy with double- and triple-drug regimens for individuals infected with the human immunodeficiency virus (HIV), but the effectiveness of these regimens in the population of patients not enrolled in clinical trials is unknown. To characterize survival following the initiation of antiretroviral therapy among HIV-infected individuals in the province of British Columbia. Prospective, population-based cohort study of patients with antiretroviral therapy available free of charge (median follow-up, 21 months). Province of British Columbia, Canada. All HIV-positive men and women 18 years of age or older in the province who were first prescribed any antiretroviral therapy between October 1992 and June 1996 and whose CD4+ cell counts were less than 0.350 x 10(9)/L. Rates of progression from initiation of antiretroviral therapy to death or a primary acquired immunodeficiency syndrome (AIDS) diagnosis for subjects who initially...

This study investigated fatigue-induced changes in neuromuscular and stride characteristics during and immediately after the 5-km running time trial. Eighteen well-trained male distance runners performed a maximal 20-m sprint test and maximal voluntary contraction (MVC) in a leg press machine before and immediately after the 5-km running time trial. In all the tests the EMG of five lower limb muscles was measured. The results of the present study showed that muscle fatigue measured in maximal exercises like 20-m sprint and MVC are not related to the fatigue induced changes during the 5-km time trial. The fatigue in the 20-m sprint test was related to the maximal 20-m pretest velocity (r=0.58, p<0.05), but the velocity loss during the 5-km time trial was inversely related to 5-km performance (r= - 0.60, p<0.05) and training volume (r= - 0.58, p<0.05). It was concluded that the fatigue in 5-km running measured pre- and postexercise at maximal effort is more related to sprint ...

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 an...

To identify sociodemographic and clinical characteristics of persons using complementary therapy in an HIV/AIDS drug treatment program and to evaluate the associations between complementary therapy use and participant characteristics. A cross-sectional study using program participants who completed an annual participant survey between 09/95 and 06/96. Surveys gathered data on use and motivations for use of complementary therapies. Complementary therapies included dietary, medicinal, tactile, and relaxation therapies. Statistical analyses were carried out using parametric and nonparametric measures and multivariate logistic analyses. Multivariate modeling considered age, income, education, time spent out of bed, and degree of pain as independent variables against complementary therapy use (Yes versus No). All reported p values are two-sided. A total of 657 participants completed an annual participant survey within the study period. Of these, 256 participants (39%) had ever used complementary therapies. Univariate analysis indicated that 195 patients (30%) had used dietary supplements, 141 (22%) had used herbal and other medicinal therapies, 145 (22%) had used tactile therapies, and 128 (20%) had used mental relaxation techniques. Multivariate analysis indicated that complementary use was independently associated with younger median age (p = .003), income >$7,300 U.S. (p = .014), having greater physical pain (p = .003), and a university education (p = .002). Use of complementary therapies in conjunction with HIV/AIDS medications appears to be most prevalent in young and highly educated individuals and to be associated with the debilitating and chronic nature of HIV disease.

To investigate baseline correlates of attempted suicide in a large cohort of young gay and bisexual men. Participants completed annual questionnaires asking demographic information, sexual behaviours, history of forced and paid sex, comfort with sexual orientation, use of illicit drugs, and validated measures of depression, social support, alcohol dependency, self-esteem and suicide ideation and attempts. Contingency table analysis and step-wise logistic regression were used to identify potential predictors of self-reported suicide attempts. Of 345 gay and bisexual men eligible for this cross-sectional analysis, 150 (43.5%) reported that they had ever considered suicide and 67 (19.4%) that they had attempted suicide at least once. After adjustment for multiple explanatory variables, the use of nitrite inhalants (poppers) (AOR = 2.37; 95% CI 1.30, 4.33), social support scores below the 75th percentile of all scores (AOR = 2.19; 95% CI 1.18, 4.09) and low or moderate self-esteem (AOR ...

To characterize the value of total lymphocyte counts in predicting risk of death among patients initiating triple combination antiretroviral therapy. Study subjects included antiretroviral-naive persons aged 18 years or older who initiated treatment with triple combination therapy between August 1 1996 and September 30 1999 in a population-based observational cohort of HIV-infected individuals. Total lymphocyte counts as well as CD4 count and plasma viral load were assessed at baseline. Separate Cox proportional hazards models were devised to evaluate the effect on survival of total lymphocyte count in lieu of or with CD4 count after adjustment for other prognostic factors including plasma viral load. A total of 733 antiretroviral-naive persons initiated triple drug combination antiretroviral therapy over the study period with a median follow-up of 29.5 months. In the first analysis, only baseline CD4 cell counts of 50-199 cells/microl or less than 50 microl were associated with an ...

To define a population-level cohort of individuals infected with the human immunodeficiency virus (HIV) in the province of British Columbia from available registries and administrative datasets using a validated case-finding algorithm. Individuals were identified for possible cohort inclusion from the BC Centre for Excellence in HIV/AIDS (CfE) drug treatment program (antiretroviral therapy) and laboratory testing datasets (plasma viral load (pVL) and CD4 diagnostic test results), the BC Centre for Disease Control (CDC) provincial HIV surveillance database (positive HIV tests), as well as databases held by the BC Ministry of Health (MoH); the Discharge Abstract Database (hospitalizations), the Medical Services Plan (physician billing) and PharmaNet databases (additional HIV-related medications). A validated case-finding algorithm was applied to distinguish true HIV cases from those likely to have been misclassified. The sensitivity of the algorithms was assessed as the proportion of ...

We investigated a chickenpox outbreak that started in an Oregon elementary school in October 2001, after public schools began phasing in a varicella vaccination requirement for enrollment. We sought to determine the rate of varicella vaccination and effectiveness and risk factors for breakthrough disease. A chickenpox case was defined as an acute maculopapulovesicular rash without other explanation occurring from October 30, 2001 through January 27, 2002 in a student without a prior history of chickenpox. We reviewed varicella vaccination records and history of prior chickenpox, and we calculated vaccine effectiveness. We evaluated the effects of age, gender, age at vaccination, and time since vaccination on risk of breakthrough disease (ie, chickenpox occurring >42 days after vaccination). Of 422 students, 218 (52%) had no prior chickenpox. Of these, 211 (97%) had been vaccinated before the outbreak. Twenty-one cases occurred in 9 of 16 classrooms. In these 9 classrooms, 18 of 152 (12%) vaccinated students developed chickenpox, compared with 3 of 7 (43%) unvaccinated students. Vaccine effectiveness was 72% (95% confidence interval: 3%-87%). Students vaccinated >5 years before the outbreak were 6.7 times (95% confidence interval: 2.2-22.9) as likely to develop breakthrough disease as those vaccinated </=5 years before the outbreak (15 of 65 [23%] vs 3 of 87 [3%]). A chickenpox outbreak occurred in a school in which 97% of students without a prior history of chickenpox were vaccinated. Students vaccinated >5 years before the outbreak were at risk for breakthrough disease. Booster vaccination may deserve additional consideration.

The goal of the present study was to characterize outcome and predictors of outcome of treatment interruption (TI) in highly active antiretroviral therapy (HAART)-treated patients. A systematic chart/database review was conducted to identify patients with nadir CD4 cell counts >200 cells/mm(3) and without acquired immunodeficiency syndrome-defining illnesses who underwent a TI. Collected data included duration and reason for TI, demographic characteristics, CD4 cell count, and plasma viral load. Human immunodeficiency virus (HIV) envelope (V3) loop genotyping was performed on plasma HIV RNA. The presence of basic residues at aa 11 and/or 25 (the "11/25" genotype) was a further possible prognostic variable of interest. Cox proportional hazards models were used to assess characteristics associated with time to HAART reinitiation after TI. A total of 208 of 4461 (4.7%) patients underwent TI. The study group consisted of 197 (94.7%) of 208 participants for whom V3 genotyping was successful. The median CD4 cell count at time of the initiation of TI was 620 cells/mm(3). A total of 59 (29.9%) patients reinitiated HAART after a median of 15 months. At the time of the reinitiation of HAART, the median plasma viral load was >100,000 copies/mL, and the median CD4 cell count was 260 cells/mm(3). Among the 197 study patients, there were 6 deaths, none of which was attributable to the TI. A total of 81% had plasma viral loads <50 copies/mL by 15 months of follow-up after reinitiation of HAART. In multivariate analysis, a nadir CD4 cell count < or =250 cells/mm(3) (risk ratio [RR], 2.79 [95% confidence interval [CI], 1.60-4.86]; P < .001) and the presence of the 11/25 genotype (RR, 2.07 [95% CI, 1.07-4.02]; P = .031) were positively and independently associated with faster time to HAART reinitiation, after adjusting for age and plasma virus load at the start of TI. Our study suggests that TI is a viable option for HIV-positive adults with nadir CD4 cell counts >250 cells/mm(3). A nadir CD4 cell count of 200-250 cells/mm(3) and the 11/25 viral genotype were found to be associated with a faster HAART reinitiation.

Clinical trials have established the efficacy of antiretroviral therapy with double- and triple-drug regimens for individuals infected with the human immunodeficiency virus (HIV), but the effectiveness of these regimens in the population of patients not enrolled in clinical trials is unknown. To characterize survival following the initiation of antiretroviral therapy among HIV-infected individuals in the province of British Columbia. Prospective, population-based cohort study of patients with antiretroviral therapy available free of charge (median follow-up, 21 months). Province of British Columbia, Canada. All HIV-positive men and women 18 years of age or older in the province who were first prescribed any antiretroviral therapy between October 1992 and June 1996 and whose CD4+ cell counts were less than 0.350 x 10(9)/L. Rates of progression from initiation of antiretroviral therapy to death or a primary acquired immunodeficiency syndrome (AIDS) diagnosis for subjects who initially received zidovudine-, didanosine-, or zalcitabine-based therapy (ERA-I) and for those who initially received therapy regimens including lamivudine or stavudine (ERA-II). A total of 1178 patients (951 ERA-I, 227 ERA-II) were eligible. A total of 390 patients died (367 ERA-I, 23 ERA-II), yielding a crude mortality rate of 33.1%. ERA-I group subjects were almost twice as likely to die as ERA-II group subjects, with a mortality risk ratio of 1.86 (95% confidence interval [CI], 1.21 -2.86; P=.005). After adjusting for Pneumocystis carinii and Mycobacterium avium prophylaxis use, AIDS diagnosis, CD4+ cell count, sex, and age, ERA-I participants were 1.93 times (95% CI, 1.25-2.97; P=.003) more likely to die than ERA-II participants. Among patients without AIDS when treatment was started, ERA-I participants were 2.50 times (95% CI, 1.59-3.93; P<.001) more likely to progress to AIDS or death than ERA-II participants. The HIV-infected individuals who received initial therapy with regimens including stavudine or lamivudine had significantly lower mortality and longer AIDS-free survival than those who received initial therapy with regimens limited to zidovudine, didanosine, and zalcitabine.

To estimate the frequency and possible predictors of patient-mediated intentional alterations in antiretroviral medication regimens in direct response to symptoms associated with antiretroviral therapy use. Cross-sectional survey of a population-based dynamic cohort of antiretroviral recipients in a province-wide HIV drug treatment program, the only source of free-of-charge antiretroviral medications in the province of British Columbia. Program participants voluntarily complete program surveys on an annual basis. Study subjects were those who responded to the annual treatment program survey between January 1 and November 1, 2001. Patients reported on the occurrence and severity of symptoms of 42 side effects of antiretroviral agents. Symptoms were classified into four subgroups based on whether they were considered subjective or objective and whether they would or would not prompt clinical action. For each of the four symptom categories, patients reported what their physician recommended in response to symptoms in that group and what the patient actually did in response to these same symptoms. Intentional nonadherence was defined as reporting either skipping or altering dosages of selective regimen components or temporary cessation of therapy that was not recommended by the physician in response to adverse drug effects in the past year. Of 638 study subjects, 70 (11%) reported intentional nonadherence with between 4% and 7.4% reporting this activity over the preceding year depending on the symptom group. Multivariate analysis revealed that a plasma viral load of <400 copies/mL (adjusted odds ratio [AOR], 0.35; 95% CI, 0.21-0.61) and completion of high school (AOR, 0.43; 95% CI, 0.24-0.78) were both inversely associated with intentional nonadherence. Those subjects reporting at least one severe symptom were more than twice as likely to report intentional nonadherence (AOR, 2.24; 95% CI, 1.16-4.33). Similarly, each additional symptom considered to be objective and to require clinical action was associated with a 25% increase in the risk of intentional nonadherence (AOR, 1.25; 95% CI, 1.10-1.43). Intentional nonadherence to antiretroviral therapy is common among persons experiencing therapy-related side effects. Although the type and severity of adverse effects impact intentional nonadherence, this activity occurs in relation to symptoms regardless of their strict clinical relevance.

This study provides population-based estimates of the incidence of constituent symptoms associated with HIV-related lipodystrophy syndrome. Possible predictors of symptomatology based on analysis of accrued cases are provided after adjustment for a broad range of personal, clinical, and treatment characteristics. Patients enrolled in a province-wide HIV/AIDS treatment program reported annually on the occurrence of lipoatrophy, lipohypertrophy, and elevated triglyceride and cholesterol levels. Of 1261 individuals who provided baseline data, 745 were available at follow-up, among whom incidence was 27% for lipoatrophy, 21% for lipohypertrophy, and 10% and 16% for increased triglyceride and cholesterol levels, respectively. In logistic multivariate modeling, incident lipoatrophy was associated with duration of stavudine (per quarter) (adjusted odds ratio [AOR] 1.18; 95% confidence interval [CI] 1.09-1.27) and having been diagnosed with AIDS (AOR 2.07; 95% CI 1.20-3.56). Lipohypertrophy risk increased with use of protease inhibitor (AOR 3.53; 95% CI 1.81-6.86) and stavudine (AOR 3.67; 95% CI 1.61-8.38). Incident cholesterol or triglyceride abnormalities were associated with protease inhibitor use (AOR 7.17; 95% CI 2.46-20.96) and duration of ritonavir (per quarter) (AOR 1.12; 95% CI 1.04-1.21). Our findings suggest high annual rates of incidence and a role of first line antiretroviral therapies in symptom development. These outcomes, in conjunction with the findings of others have important implications for evolving treatment patterns.

To identify associations between HIV-related experience and patterns of service provision, physicians across Canada were solicited by mail to register in a national network of HIV/AIDS care givers. Respondents provided data about: personal, demographic and practice characteristics; the number of HIV-positive patients ever seen; the nature of the HIV-positive client population; and services provided to HIV-positive patients. Univariate techniques provided a demographic and professional profile of participating physicians. Logistic regression was used to identify associations between level of HIV-related experience and the provision of patient services. The 566 registered physicians have provided care to 56,378 HIV-infected persons and represent every province and territory in Canada. Multivariate analysis revealed that highly experienced physicians were more likely to provide all 3 types of services considered, to practise in Montreal, Vancouver or Toronto, and to be medical specialists (all P < 0.001).

An anonymous questionnaire was mailed to 3 groups of physicians in British Columbia: 659 registrants of a province-wide human immunodeficiency virus (HIV) drug treatment programme (Group 1); 765 who had had a patient test positive for HIV (Group 2); and a random sample of 484 (Group 3). Questionnaires provided data about: physician's demographic and personal characteristics; HIV-related patient care experience; and 12 knowledge-based items. Responses were received from 65% of Group 1, 68% of Group 2 and 70% of Group 3, with complete information received from 38% of Group 1 and 50% of Groups 2 and 3. Summary knowledge scores were computed by comparing physician responses to recommendations of contemporary guidelines. Regression techniques identified associations between physician characteristics and knowledge scores. Multivariate analysis revealed an inverse relationship between knowledge and physician age in all groups (all P < 0.01). Increased knowledge was associated with the number of currently active HIV-positive patients in Groups 1 and 2 (all P < 0.001), and lack of specialization in Groups 2 and 3 (both P < 0.001).

To provide population-based incidence estimates for constituent symptoms of human immundeficiency virus (HIV)-related lipodystrophy syndrome and to identify possible independent predictors of accrued cases. Prospective population-based cohort. Methods Study subjects were antiretroviral-naïve individuals who initiated treatment between October 1998 and May 2001 and provided completed self-reported data regarding the occurrence of lipoatrophy, lipohypertrophy and increased triglyceride and cholesterol levels. Possible predictors of incident lipoatrophy, lipohypertrophy, dyslipidaemia and mixed lipodystrophy (symptoms of both lipoatrophy and lipohypertrophy) were identified using logistic regression modelling. A sub-analysis restricted to subjects retaining original treatment at study completion was conducted using similar methods. Among the 366 study subjects, cumulative incidence was 29% for lipoatrophy, 23% for lipohypertrophy, 9% for dyslipidaemia, and 13% for mixed lipodystrophy after a median duration of 12 months of antiretroviral therapy. In an intentto-treat analysis incident lipoatrophy and lipohypertrophy were independently associated with initiation of protease inhibitor (PI)-containing regimens, (adjusted odds ratio [AOR] = 1.94; 95% CI: 1.25-3.03 and AOR = 1.76; 95% CI: 1.09-2.85, respectively) and female gender (AOR = 2.06; 95% CI: 1.03-4.12 and AOR = 2.36; 95% CI: 1.17-4.74, respectively). Both mixed lipodystrophy and reported dyslipidaemia were associated only with PI inclusion in the initial regimen (AOR = 2.27; 95% CI: 1.14-4.53 and AOR = 2.14; 95% CI: 1.26-3.65, respectively). Similar results were obtained in analysis of individuals retained in initial treatment groups throughout follow-up. Incident morphological and lipid abnormalities are common among individuals initiating first-time antiretroviral therapy. Use of PI was consistently associated with all lipodystrophy-related abnormalities after adjustment for a broad range of patient personal, clinical and treatment characteristics.

Intubation at the site of accident is often necessary for patients who have sustained significant head injuries. Propofol can attenuate the hypertensive response to intubation, and cause hypotension in anaesthetic doses which can be greatly exaggerated in hypovolaemic patients. We studied nine patients with isolated head injuries and 11 multiply injured patients with associated head injuries. Patients were resuscitated and then intubated with a small dose of propofol, titrated to ensure unconciousness, and then suxamethonium. In neither group was there a statistically significant fall in blood pressure afterwards although the multiply injured patients tended have greater falls. We conclude that propofol used thus does not cause clinically important hypotension in these potentially unstable patients, but only doctors with suitable anaesthetic and pre-hospital experience should attempt it.

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.