HIV testing of patients: let's waive the waiver.
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Canada↗
Biomedical subjects
M T Schechter
Publications and source records attributed to M T Schechter.
Determinants of geographic mobility among participants in a population-based HIV/AIDS drug treatment program.
This study was undertaken to determine the geographic distribution and patterns of migration of persons with HIV in British Columbia. Our analysis was restricted to all HIV-positive men and women aged 18 years and over who had completed a participant survey and were enrolled in the HIV/AIDS Drug Treatment Program between September 1992 and September 1997. Patterns of migration were determined by examining participants whose postal code changed between July 1995 and September 1997. Statistical analysis were carried out using both parametric and non-parametric methodologies. Stepwise logistic regression was used to determine baseline predictors of migration. The final multivariate model revealed that residing in a census subdivision with a population less than 100,000, being heterosexual, acquiring HIV through intravenous drug use, and the absence of AIDS at baseline were all independently associated with moving census subdivisions during the period of observation. In summary, our analyses demonstrate the need for the continued study of the evolving geography and migration patterns of persons with HIV.
Adult↗
Prevalence of primary HIV drug resistance among seroconverters during an explosive outbreak of HIV infection among injecting drug users.
OBJECTIVES: This study examined the frequency of transmission of drug resistant HIV in the population of injecting drug users (IDU) in Vancouver, Canada during a period of particularly high virus transmission. DESIGN: All subjects enrolled in the Vancouver Injection Drug Users Study who seroconverted from HIV negative to positive status (n = 61) between December 1996 and February 1998 were eligible for analysis. The first seropositive sample from 57 individuals with plasma samples available was analyzed for resistance to antiretroviral agents by population based sequencing of the HIV protease and reverse transcriptase genes. METHODS: Plasma viral RNA was extracted and the viral reverse transcriptase and protease regions were amplified by nested reverse transcription-PCR. The presence of mutations associated with antiretroviral drug resistance was assessed by automated sequence analysis. RESULTS: Protease and reverse transcriptase sequences were successfully obtained from the 57 recent seroconverters. No cases of transmission of variants associated with significant resistance to protease inhibitors or nucleoside and non-nucleosides reverse transcriptase inhibitors were detected. CONCLUSION: The frequency of transmission of drug resistant HIV amongst these recently infected IDU is extremely low, with no protease or reverse transcriptase inhibitor resistant strains detected soon after seroconversion. The data provide no rationale for withholding treatment from this already marginalized population.
Anti-HIV Agents↗
Systolic and diastolic learning: an analogy to the cardiac cycle.
It has been observed that the active-passive classification of adult learning can be viewed in terms of a systolic-diastolic model. This model represents an analogy to the cardiac cycle and the work done by the heart during these two phases of the cycle. The determinants of systolic and diastolic learning can be compared to the determinants of cardiac function: preload, afterload and contractility. Similarly, dysfunction in these two phases of learning can be compared to cardiac dysfunction from a pathophysiologic perspective.
Adult↗
Do needle exchange programmes increase the spread of HIV among injection drug users?: an investigation of the Vancouver outbreak.
OBJECTIVE: An association between needle exchange attendance and higher HIV prevalence rates among injecting drug users (IDU) in Vancouver has been interpreted by some to suggest that needle exchange programmes (NEP) may exacerbate HIV spread. We investigated this observed association to determine whether needle exchange was causally associated with the spread of HIV. DESIGN AND METHOD: Prospective cohort study of 694 IDU recruited in the downtown eastside of Vancouver. Subjects were HIV-negative at the time of recruitment and had injected illicit drugs within the previous month. RESULTS: Of 694 subjects, the 15-month cumulative HIV incidence was significantly elevated in frequent NEP attendees (11.8+/-1.7 versus 6.2+/-1.5%; log-rank P = 0.012). Frequent attendees (one or more visits per week) were younger and were more likely to report: unstable housing and hotel living, the downtown eastside as their primary injecting site, frequent cocaine injection, sex trade involvement, injecting in 'shooting galleries', and incarceration within the previous 6 months. The Cox regression model predicted 48 seroconversions among frequent attendees; 47 were observed. Although significant proportions of subjects reported obtaining needles, swabs, water and bleach from the NEP, only five (0.7%) reported meeting new friends or people there. When asked where subjects had met their new sharing partners, only one out of 498 respondents cited the needle exchange. Paired analysis of risk variables at baseline and the first follow-up visit did not reveal any increase in risk behaviours among frequent attendees, regardless of whether they had initiated drug injection after establishment of the NEP. CONCLUSIONS: We found no evidence that this NEP is causally associated with HIV transmission. The observed association should not be cited as evidence that NEP may promote the spread of HIV. By attracting higher risk users, NEP may furnish a valuable opportunity to provide additional preventive/support services to these difficult-to-reach individuals.
Adult↗
Improved survival among HIV-infected patients after initiation of triple-drug antiretroviral regimens.
BACKGROUND: The efficacy of triple-drug antiretroviral regimens in the treatment of patients infected with HIV has been established in several randomized clinical trials. However, the effectiveness of these new regimens in patient populations outside clinical trials remain unproven. This study compared mortality and AIDS-free survival among HIV-infected patients in British Columbia who were treated with double- and triple-drug regimens. METHODS: The authors used a prospective, population-based cohort design to study a population of HIV-positive men and women 18 years or older for whom antiretroviral therapy was first prescribed between Oct. 1, 1994, and Dec. 31, 1996; all patients were from British Columbia. Rates of progression from the initiation of antiretroviral therapy to death or to diagnosis of primary AIDS were determined for patients who initially received an ERA-II regimen (2 nucleoside analogue reverse transcriptase inhibitors [NRTIs] including lamivudine or stavudine, or both) and for those who initially received an ERA-III regimen (triple-drug regimen consisting of 2 NRTIs and a protease inhibitor [indinavir, ritonavir or saquinavir] or a non-NRTI [nevirapine]). RESULTS: A total of 500 men and women (312 receiving an ERA-III regimen and 188 an ERA-III regimen) were eligible. Patients in the ERA-III group survived significantly longer than those in the ERA-II group. As of Dec. 31, 1997, 40 patients had died (35 in the ERA-II group and 5 in the ERA-III group), for a crude mortality rate of 8.0%. The cumulative mortality rates at 12 months were 7.4% (95% confidence interval [CI] 5.9% to 8.9%) for patients in the ERA-II group and 1.6% (95% CI 0.7% to 2.5%) for those in the ERA-III group (log rank p = 0.003). The likelihood of death was more than 3 times higher among patients in the ERA-II group (mortality risk ratio 3.82 [95% CI 1.48% to 9.84], p = 0.006). After adjustment for prophylaxis for Pneumocystis carinii pneumonia or Mycobacterium avium infection, AIDS diagnosis, CD4+ cell count, sex and age at initiation of therapy, the likelihood of death among patients in the ERA-II group was 3.21 times higher (95% CI 1.24 to 8.30, p = 0.016) than in the ERA-III group. Cumulative rates of progression to AIDS or death at 12 months were 9.6% (95% CI 7.7% to 11.5%) in the ERA-II group and 3.3% (95% CI 1.8% to 4.8%) in the ERA-III group (log rank p = 0.006). After adjustment for prognostic variables (prophylaxis for P. carinii pneumonia or M. avium infection, CD4+ cell count, sex and age at initiation of treatment), the likelihood of progression to AIDS or death at 12 months among patients in the ERA-II group was 2.37 times higher (95% CI 1.04 to 5.38, p = 0.040) than in the ERA-III group. INTERPRETATION: This population-based cohort study confirms that patients initially treated with a triple-drug antiretroviral regimen comprising 2 NRTIs plus protease inhibitor or a non-NRTI have a lower risk of morbidity and death than patients treated exclusively with 2 NRTIs.
Acquired Immunodeficiency Syndrome↗
The social determinants of emergency department and hospital use by injection drug users in Canada.
OBJECTIVE: The aim of this study was to describe the relationship between sociodemographic characteristics and human immunodeficiency (HIV) status of a cohort of injection drug users (IDUs) on their self-reported health service utilization. DESIGN: Interviewer-administered questionnaire. METHODS: IDUs who had injected illicit drugs within the previous month were recruited through street outreach. They underwent serology for HIV-1 and questionnaires on demographics, drug using behaviors, housing status, and health service utilization (hospitalization overnight and emergency department visits) in the previous 6 months. Logistic regression analysis was used to identify independent associations with the use of health services. RESULTS: Of 1,103 cohort participants, 65% were male, 63% were white, and 23% were HIV positive. Cocaine was the most frequently injected drug used. Almost half (47%) had used health services in the previous 6 months. The following variables were associated independently with health service utilization (adjusted odds ratio; 95% confidence interval): unstable housing, defined as living primarily in a hotel, boarding room, or transition house or on the street in the past 6 months (1.44; 1.11-1.86); female gender (1.45; 1.11-1.89); HIV-positive status (1.43; 1.06-1.92); injection of cocaine (1.50; 1.12-2.02); and primary care I physician visit in past 6 months (1.91; 1.39-2.64). CONCLUSION: IDUs with unstable housing were more likely to report emergency department and hospital use, which may be a reflection of their disorganized lifestyle or poorer health status. Further studies are required to assess the effect on the health status and health care use of IDUs of interventions that increase the availability of safe, affordable housing.
Adult↗
Social inequalities in male mortality amenable to medical intervention in British Columbia.
The objective of this study is to examine the rates of mortality among different social classes and socioeconomic groups of British Columbian males from causes of death amenable to medical intervention. We examined the rates of avoidable mortality from the causes of death published by Charlton, excluding causes of death restricted to women as well as perinatal deaths. For the purposes of our study, we determined a population at risk using 20% samples of occupational data for men from the 1981, 1986 and 1991 censuses conducted by Statistics Canada. For the analysis of mortality by social class, individuals were divided into five social class levels based on occupation using an adaptation of the UK Registrar General's Social Class Scale. In addition, three levels of socioeconomic analysis were performed using the Blishen Index classification system. Once individuals were assigned to a social class in each classification system, the death rates from each amenable cause was calculated and standardized to the total population. For almost every cause of death examined, the rate of mortality was higher in individuals of lower social and socioeconomic classes than in individuals of the upper social and socioeconomic classes. These results were consistent regardless of the social class component, education, occupation, or income was being measured. The mortality gradient was most notable in deaths due to hypertensive heart disease, tuberculosis, asthma and pneumonia and bronchitis. Due to the fact that these causes of death were observed to be consistently higher in the lower social classes, we feel that specific measures aimed at improving survival from these conditions in lower social classes could help to amend the social class disparity.
Adolescent↗
HIV-associated risk factors among young Canadian Aboriginal and non-Aboriginal men who have sex with men.
Young Aboriginal men face marginalization distinct in cause but similar in pattern to those seen among men who have sex with men (MSM) and may be at increased risk for HIV infection. We compared sociodemographic characteristics and risk taking behaviours associated with HIV infection among MSM of Aboriginal and non-Aboriginal descent. Data for this comparison were gathered from baseline questionnaires completed by participants in a cohort study of young MSM. Data collection included: demographic characteristics such as age, length of time residing in the Vancouver region, housing, employment, income and income sources; mental health and personal support; instances of forced sex and sex trade participation and; sexual practices with regular and casual male sex partners. Data were available for 57 Aboriginal and 624 non-Aboriginal MSM. Aboriginal MSM were significantly less likely to be employed, more likely to live in unstable housing, to have incomes of <$10,000 and to receive income assistance than non-Aboriginals (all P<0.01). Aboriginals also had higher depression scores (P<0.01), were more likely to report non-consensual sex (P=0.03), sexual abuse during childhood (P=0.04) and having been paid for sex (P<0.01). In the past year they were no more likely to have had sex with a male partner they knew to be HIV positive, to have had more than 50 male partners or to have unprotected anal insertive or receptive intercourse with their male partners (all P>0.05). Our data indicate that among MSM, Aboriginal men are at increased risk of antecedent risk factors for HIV infection including sexual abuse, poverty, poor mental health and involvement in the sex trade.
Adolescent↗
One world, one hope: the cost of providing antiretroviral therapy to all nations.
OBJECTIVE: To estimate the potential direct cost of making triple combination antiretroviral therapy widely available to HIV-positive adults and children living in countries throughout the world. METHODS: For each country, antiretroviral costs were obtained by multiplying the annual cost of triple antiretroviral therapy by the estimated number of HIV-positive persons accessing therapy. Per capita antiretroviral costs were computed by dividing the antiretroviral costs by the country's total population. The potential economic burden was calculated by dividing per capita antiretroviral costs by the gross national product (GNP) per capita. All values are expressed in 1997 US dollars. RESULTS: The potential cost of making triple combination antiretroviral therapy available to HIV-positive individuals throughout the world was estimated to be over US$ 65.8 billion. By far the greatest financial burden was on sub-Saharan Africa. The highest per capita drug cost in this region would be incurred in the subregions of Southern Africa (US$ 149) followed by East Africa (US$ 116), Middle Africa (US$ 44), and West Africa (US$ 42). In the Americas, subregional data indicated the highest per capita drug cost would be in the Latin Caribbean (US$ 22), followed by the Caribbean (US$ 17), Andean Area (US$ 7), the Southern Cone (US$ 6), North America (US$ 6), and Central American Isthmus (US$ 5). In Asia and Europe the percentage of the GNP necessary to finance drug therapy was less than 1% in most countries examined. CONCLUSION: Our results demonstrate that the cost of making combination antiretroviral therapy available worldwide would be exceedingly high, especially in countries with limited financial resources.
Adult↗
Models of survival in HIV infection and their use in the quantification of treatment benefits.
Because acquired immunodeficiency syndrome (AIDS) is a shifting endpoint and sufficient follow-up data now allow modeling of survival time (i.e., time from human immunodeficiency virus (HIV) seroconversion to death), the authors evaluated non-parametric and parametric models of mortality with the use of data from 554 seropositive participants in the Vancouver Lymphadenopathy-AIDS Study. The authors then applied these models to quantify treatment benefits at the national level in Canada, using back-calculation and forward-projection based on death registries. The study revealed that the lognormal model better describes survival time than the Weibull model. Relative to observations prior to 1987, later observations (in the era of treatment) revealed a statistically significant change in disease progression: the median survival time increased from 10.1 to 12.0 years, but no further survival improvements were observed in the early 1990s. Concurrent with the increase in availability of treatment, the authors have observed pronounced treatment benefits at the national level: prior to 1995, approximately 1,500 deaths were prevented and 4,200 person-years of life were saved. Also, mortality rates were observed to level off in the mid-1990s due to the shape of the historical HIV infection curve and the accumulating availability of treatment in Canada.
Canada↗
Determinants of sexual risk-taking among young HIV-negative gay and bisexual men.
Data from a cohort of young HIV-negative gay and bisexual men were analyzed to identify determinants of sexual risk-taking at baseline. Gay/bisexual men aged between 18 and 30 completed a self-administered questionnaire including demographics, depression, social support, substance use, and consensual versus nonconsensual sex. Risk-takers were defined as those who had unprotected anal sex with casual male sex partners in the previous year; non-risk-takers were defined as those who reported consistent condom use during anal sex with all male partners in the previous year. Logistic regression was used to identify independent predictors of sexual risk-taking. Of 439 men studied, risk-takers had less education, a higher depression score, less social support, and were more likely to report nonconsensual sex and recreational drug use relative to non-risk-takers. Independent predictors of sexual risk-taking were low education, nitrite use, low social support (adjusted odds ratio [AOR]=1.65; 95% CI, 1.04-2.59), and nonconsensual sex experienced as a youth or adult (AOR=1.85; 95% CI, 1.15-2.96). Young gay/bisexual men reporting nonconsensual sex, low social support, or nitrite use were significantly more likely to have recently had unprotected anal sex with casual partners. HIV prevention programs aimed at young gay/bisexual men should include sexual abuse counselling and foster community norms supporting safer sex practices.
Adult↗
Barriers to use of free antiretroviral therapy in injection drug users.
CONTEXT: In British Columbia, human immunodeficiency virus (HIV)-infected persons eligible for antiretroviral therapy may receive it free but the extent to which HIV-infected injection drug users access it is unknown. OBJECTIVE: To identify patient and physician characteristics associated with antiretroviral therapy utilization in HIV-infected injection drug users. DESIGN: Prospective cohort study with record linkage between survey data and data from a provincial HIV/AIDS (acquired immunodeficiency syndrome) drug treatment program. SETTING: British Columbia, where antiretroviral therapies are offered free to all persons with HIV infection with CD4 cell counts less than 0.50 x 10(9)/L (500/microL) and/or HIV-1 RNA levels higher than 5000 copies/mL. SUBJECTS: A total of 177 HIV-infected injection drug users eligible for antiretroviral therapy, recruited through the prospective cohort study since May 1996. MAIN OUTCOME MEASURES: Patient use of antiretroviral drugs through the provincial drug treatment program and physician experience treating HIV infection. RESULTS: After a median of 11 months after first eligibility, only 71 (40%) of 177 patients had received any antiretroviral drugs, primarily double combinations (47/71 [66%]). Both patient and physician characteristics were associated with use of antiretroviral drugs. After adjusting for CD4 cell count and HIV-1 RNA level at eligibility, odds of not receiving antiretrovirals were increased more than 2-fold for females (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.08-5.93) and 3-fold for those not currently enrolled in drug or alcohol treatment programs (OR, 3.49; 95% CI, 1.45-8.40). Younger drug users were less likely to receive therapy (OR, 0.47/10-y increase; 95% CI, 0.28-0.80). Those with physicians having the least experience treating persons with HIV infection were more than 5 times less likely to receive therapy (OR, 5.55; 95% CI, 2.49-12.37). CONCLUSIONS: Despite free antiretroviral therapy, many HIV-infected injection drug users are not receiving it. Public health efforts should target younger and female drug users, and physicians with less experience treating HIV infection.
Adult↗
The antiviral effect of ritonavir and saquinavir in combination amongst HIV-infected adults: results from a community-based study.
OBJECTIVE: To characterize the antiviral effect and predictors of response to ritonavir and saquinavir-based antiretroviral combination therapy. DESIGN: Intent-to-treat analysis with suppression of plasma viral load to levels below 2.7 log10 copies/ml as the main outcome measure. PATIENTS: All adult HIV-positive individuals in the province of British Columbia who started taking ritonavir and saquinavir (each at 600 mg twice daily) in combination from 1 September 1996 to 28 February 1997, with a minimum of two plasma viral load measurements, one at baseline and one after the initiation of therapy. RESULTS: A total of 58 participants were prescribed ritonavir and saquinavir. The median plasma viral load at entry was 4.80 log10 copies/ml (interquartile range, 4.51-5.15 log10 copies/ml). A total of 29 (50%) subjects demonstrated a decrease in plasma viral load to levels below 2.7 log10 copies/ml. This level of suppression was associated with higher baseline CD4 cell counts (P=0.022) and no prior exposure to protease inhibitors (P=0.001). After controlling for baseline CD4 cell count and plasma viral load, participants naive to protease inhibitors were almost seven times (odds ratio, 6.99; 95% confidence interval, 1.85-26.39; P=0.004) more likely to suppress their plasma viral load to below 2.7 log10 copies/ml than those who had previously used protease inhibitors. CONCLUSION: Our analysis demonstrates that a ritonavir and saquinavir-based combination can produce a substantial decrease in plasma viral load with half of the participants decreasing their plasma viral load to below the limit of quantification of the assay. This response, however, is seriously compromised by prior exposure to protease inhibitors.
Adult↗
Antiviral effect of double and triple drug combinations amongst HIV-infected adults: lessons from the implementation of viral load-driven antiretroviral therapy.
OBJECTIVE: To study the antiviral effect and predictors of response to two- and three-drug regimens amongst antiretroviral-naive individuals using an intent-to-treat analysis. MAIN OUTCOME MEASURE: Suppression of plasma viral load to < 500 copies/ml. PATIENTS: A total of 420 (264 double drug, 156 triple drug) individuals in a province-wide treatment programme were studied. RESULTS: A decrease in plasma viral load to < 500 copies/ml was documented in 197 (47%) subjects. This was independently associated with a lower baseline plasma viral load (odds ratio, 3.67; 95% confidence interval, 2.13-6.30) and initiation onto a three-drug regimen (odds ratio, 3.86; 95% confidence interval, 2.24-6.66). Median plasma viral load failed to reach < 500 copies/ml and in fact rebounded in the two-drug group. In contrast, 91 (58%) subjects receiving three drugs reached < 500 copies/ml during the study period. CONCLUSION: These results support the use of powerful triple drug regimens as initial therapy in HIV-infected individuals.
Adult↗
Improved survival among HIV-infected individuals following initiation of antiretroviral therapy.
CONTEXT: 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. OBJECTIVE: To characterize survival following the initiation of antiretroviral therapy among HIV-infected individuals in the province of British Columbia. DESIGN: Prospective, population-based cohort study of patients with antiretroviral therapy available free of charge (median follow-up, 21 months). SETTING: Province of British Columbia, Canada. PATIENTS: 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. MAIN OUTCOME MEASURES: 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). RESULTS: 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. CONCLUSION: 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.
AIDS-Related Opportunistic Infections↗
Factors associated with frequent needle exchange program attendance in injection drug users in Vancouver, Canada.
The objective of this study was to identify factors associated with frequent needle exchange program (NEP) attendance by injection drug users (IDUs) in Vancouver, Canada. Data were examined from a case control study of recent HIV infection. IDUs with documented HIV seroconversion after January 1, 1994 (n = 89) and seronegative controls with two documented HIV-negative test results in the same period (n = 192) were asked about demographic and social information, drug injection and sexual behavior, and NEP attendance. Logistic regression was used to examine the effect of multiple variables on NEP attendance while adjusting for HIV status and other potential confounders. Frequent (> 1 time/week) versus nonfrequent (< or = 1 time/week) NEP attenders did not differ with respect to gender, age, ethnicity, education, or HIV serostatus. For men, multivariate analysis showed that frequent cocaine injection was the only variable independently associated with NEP attendance (adjusted odds ratio [AOR] = 3.9; 95% confidence interval [CI] = 1.8-8.3); for women, independently associated variables were frequency of any drug injection (AOR = 5.5; 95% CI = 1.7-17), shooting gallery attendance (AOR = 11.5; 95% CI = 2.2-66), and having a nonlegal source of income (AOR = 3.4; 95% CI = 1.0-12). Borrowing used needles was associated with frequent NEP attendance in the univariate analysis. The NEP in Vancouver attracts IDUs who are frequent injectors (especially men using cocaine) and who have high-risk behaviors or an unstable lifestyle. This finding reinforces the role of NEPs as potential focal points for intervention in this hard-to-reach population.
Adult↗