Martin T. Schechter

Needle exchange is not enough: lessons from the Vancouver injecting drug use study

Objective: To describe prevalence and incidence of HIV‐1, hepatitis C virus (HCV) and risk behaviours in a prospective cohort of injecting drug users (IDU). Setting: Vancouver, which introduced a needle exchange programme (NEP) in 1988, and currently exchanges over 2 million needles per year. Design: IDU who had injected illicit drugs within the previous month were recruited through street outreach. At baseline and semi‐annually, subjects underwent serology for HIV‐1 and HCV, and questionnaires on demographics, behaviours and NEP attendance were completed. Logistic regression analysis was used to identify determinants of HIV prevalence. Results: Of 1006 IDU, 65% were men, and either white (65%) or Native (27%). Prevalence rates of HIV‐1 and HCV were 23 and 88%, respectively. The majority (92%) had attended Vancouvers NEP, which was the most important syringe source for 78%. Identical proportions of known HIV‐positive and HIV‐negative IDU reported lending used syringes (40%). Of HIV‐negative IDU, 39% borrowed used needles within the previous 6 months. Relative to HIV‐negative IDU, HIV‐positive IDU were more likely to frequently inject cocaine (72 versus 62%; P < 0.001). Independent predictors of HIV‐positive serostatus were low education, unstable housing, commercial sex, borrowing needles, being an established IDU, injecting with others, and frequent NEP attendance. Based on 24 seroconversions among 257 follow‐up visits, estimated HIV incidence was 18.6 per 100 person‐years (95% confidence interval, 11.1‐26.0). Conclusions: Despite having the largest NEP in North America, Vancouver has been experiencing an ongoing HIV epidemic. Whereas NEP are crucial for sterile syringe provision, they should be considered one component of a comprehensive programme including counselling, support and education.

Spinal bone loss and ovulatory disturbances

Abstract Background. Osteoporosis develops in women with estrogen deficiency and amenorrhea who lose bone at an accelerated rate. It Is not known to what extent bone loss differs between ovulatory women with regular menstrual cycles who are training intensely and those who are sedentary. Methods. We measured the density of cancellous spinal bone from the 12th thoracic vertebra to the 3rd lumbar vertebra by quantitative computed tomography on two occasions one year apart in 66 premenopausal women 21 to 42 years of age. All the women had two consecutive ovulatory cycles immediately before entering the study. Twenty-one women were training for a marathon, 22 ran regularly but less intensively, and 23 had normal levels of activity. The lengths of the womens menstrual cycles and luteal phases, diet, exercise levels, and hormonal levels were also determined. We defined ovulatory disturbances as anovulatory cycles and cycles with short luteal phases. Results. The mean (±SD) spinal bone density in the 66 women d...

The psychological consequences of predictive testing for Huntington's disease.

Abstract Background. Advances in molecular genetics have led to the development of tests that can predict the risk of inheriting the genes for several adult-onset diseases. However, the psychological consequences of such testing are not well understood. Methods. The 135 participants in the Canadian program of genetic testing to predict the risk of Huntingtons disease were followed prospectively in three groups according to their test results: the increased-risk group (37 participants), the decreased-risk group (58 participants), and the group with no change in risk (the no-change group) (40 participants). All the participants received counseling before and after testing. Standard measures of psychological distress (the General Severity Index of the Symptom Check List 90-R), depression (the Beck Depression Inventory), and well-being (the General Well-Being Scale) were administered before genetic testing and again at intervals of 7 to 10 days, 6 months, and 12 months after the participants received their t...

Decline in deaths from AIDS due to new antiretrovirals

We determined whether availability of new antiretroviral treatments has had any impact on the rate of death for people with HIV-1 infection. Distribution of antiretroviral drugs in British Columbia, Canada, is free of charge through the Centre for Excellence in HIV/AIDS Treatment Programme. For physicians to prescribe antiretrovirals, they must complete a participant enrolment form that serves as the drug prescription. Individuals infected with HIV-1 are eligible to receive antiretroviral therapy from this programme if they have at least one CD4 cell count less than 0·5 10/L. Until December, 1995, monotherapy was made available to participants with CD4 counts less than 0·5 10/L, while double combination therapy was made available to those with CD4 counts of less than 0·35 10/L. After December, 1995, double combination treatment was made available to everyone with CD4 counts less than 0·5 10/L. Viral-loaddriven antiretroviral treatment and triple combination therapy became available after June, 1996. Of the five new medications introduced in 1996, lamivudine became available in January, saquinavir in June, stavudine in July, and indinavir and ritonavir in September. Patterns of mortality were assessed by comparing changes in death rates for those individuals on antiretroviral therapy by quarter and CD4-count groupings (0·1 10/L, 0·1–0·34 10/L, and 0·35–0·49 10/L). Mortality data were obtained through regular surveillance and computerised record linkages with Division of Vital Statistics of the British Columbia Ministry of Health. Population figures were based on the number of programme participants actively on antiretroviral therapy. Rates were expressed as deaths per 1000 active participants and were calculated over a 3-year period from January, 1994 to December, 1996. There were 604 deaths during this period among individuals ever on antiretroviral therapy; of these, 475 deaths (79%) were attributed to participants with CD4 counts less than 0·1 10/L. There was a significant decline in programme mortality rates since the first quarter of 1994 (trend test p<0·001). On average, the rate of death for those on antiretroviral treatment declined at a rate of 1·7 deaths per 1000 participants per quarter or from 18·9 deaths per 1000 participants in the first quarter of 1994 to 5·7 deaths per 1000 participants in the last quarter of 1996. As shown in the figure, the greatest decline in mortality was experienced in those participants with CD4 counts less than 0·1 10/L (trend test p<0·001). On average, the death rate for participants with CD4 counts of less than 0·1 10/L declined at a rate of 3·5 deaths per 1000 participants per quarter—ie, from 62·0 to 19·8 deaths per 1000 participants from the first quarter of 1994 to the last quarter of 1996. Although there was a decline in the death rates for other two CD4-count groups, the rates were not statistically significant. Delayed reporting was not likely to affect our analysis. The vast majority of deaths were reported through active follow-up. In this analysis, data on 536 (89%) deaths were obtained through physician and hospital reports and data on 68 (11%) were obtained through linkages. Furthermore, in a subanalysis of 179 deaths obtained through physician and hospital reports over a 1-year period ending on June 30, 1996, we found that the median follow-up time between the actual date of death and the date of reporting was 7 days (interquartile range 5–11 days). Our data show a substantial decrease in AIDS-related mortality in the province of British Columbia. The decline in mortality coincides with the availability of lamivudine in the province through open access and with the expanded use of double combination antiretroviral therapy. We believe this mortality trend will likely continue as protease inhibitors and non-nucleoside reverse transcriptase inhibitors are used to greater extent within the treatment programme.

Corticosteroids Prevent Early Deterioration in Patients with Moderately Severe Pneumocystis carinii Pneumonia and the Acquired Immunodeficiency Syndrome (AIDS)

OBJECTIVE To determine whether oral corticosteroids can prevent early deterioration in patients with acquired immunodeficiency syndrome (AIDS)-related Pneumocystis carinii pneumonia. DESIGN Prospective, double-blind, placebo-controlled, randomized trial. METHODS Included patients were having their first P. carinii pneumonia episode, had no other known active pulmonary pathology, had no contraindications for corticosteroids, received no anti-P. carinii pneumonia medications for more than 48 hours, and had oxygen saturation by pulse oximetry of 85% or more and less than 90% at rest or a 5-percentage-point decrease in oxygen saturation with exercise while breathing room air. Consenting subjects were randomly assigned to prednisone, 60 mg/d for 7 days, followed by a progressive tapering over 14 days or to an identical placebo. Early deterioration, the endpoint of the trial, was defined as a 10% decrease in baseline oxygen saturation on day 3 or thereafter. The cases of patients developing early deterioration were considered to be failures of treatment; the code was then broken, and the patients treatment was left to the judgment of the treating physician. Sequential analysis was done with the primary variable being development of early deterioration. RESULTS The trial was terminated 5 April 1989 on the basis of the sequential analysis when a total of nine episodes of early deterioration had occurred in the first 37 patients at an overall significance level of P = 0.0136. A total of 8 of 19 placebo-treated patients (42.1%) developed early deterioration compared with only 1 of 18 patients (5.6%) treated with corticosteroids. Baseline characteristics were not statistically different between the two treatment groups. The adjusted odds ratio for the treatment effect was 5.87 (95% CI, 1.27 to 27.4). The adjusted point estimates for the probability of early deterioration in the placebo and corticosteroid groups were 43% and 12%, respectively. All 8 patients in the placebo group developing early deterioration recovered rapidly with addition of corticosteroid treatment. The single patient with early deterioration in the corticosteroid group died on day 6 from overwhelming P. carinii pneumonia, as documented at autopsy. The corticosteroid group had an increased exercise tolerance on day 7 that persisted at day 30. CONCLUSION Oral corticosteroids prevent early deterioration and increase exercise tolerance in patients with moderately severe AIDS-related P. carinii pneumonia.

Diacetylmorphine versus Methadone for the Treatment of Opioid Addiction

BACKGROUND Studies in Europe have suggested that injectable diacetylmorphine, the active ingredient in heroin, can be an effective adjunctive treatment for chronic, relapsing opioid dependence. METHODS In an open-label, phase 3, randomized, controlled trial in Canada, we compared injectable diacetylmorphine with oral methadone maintenance therapy in patients with opioid dependence that was refractory to treatment. Long-term users of injectable heroin who had not benefited from at least two previous attempts at treatment for addiction (including at least one methadone treatment) were randomly assigned to receive methadone (111 patients) or diacetylmorphine (115 patients). The primary outcomes, assessed at 12 months, were retention in addiction treatment or drug-free status and a reduction in illicit-drug use or other illegal activity according to the European Addiction Severity Index. RESULTS The primary outcomes were determined in 95.2% of the participants. On the basis of an intention-to-treat analysis, the rate of retention in addiction treatment in the diacetylmorphine group was 87.8%, as compared with 54.1% in the methadone group (rate ratio for retention, 1.62; 95% confidence interval [CI], 1.35 to 1.95; P<0.001). The reduction in rates of illicit-drug use or other illegal activity was 67.0% in the diacetylmorphine group and 47.7% in the methadone group (rate ratio, 1.40; 95% CI, 1.11 to 1.77; P=0.004). The most common serious adverse events associated with diacetylmorphine injections were overdoses (in 10 patients) and seizures (in 6 patients). CONCLUSIONS Injectable diacetylmorphine was more effective than oral methadone. Because of a risk of overdoses and seizures, diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available. (ClinicalTrials.gov number, NCT00175357.)

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.

Factors associated with persistent high-risk syringe sharing in the presence of an established needle exchange programme.

Vancouver has experienced an explosive HIV epidemic despite the presence of a needle exchange programme (NEP). We sought possible explanations for high-risk syringe sharing among Vancouver injection drug users over the period January 1999 to October 2000. Overall, 14% of participants reported high-risk sharing. Although acquiring needles exclusively from the NEP was independently associated with less sharing, we identified several risk factors for persistent sharing, including difficulty accessing sterile needles, bingeing, and frequent cocaine injection.

Displacement of Canada's largest public illicit drug market in response to a police crackdown

Background: Law enforcement is often used in an effort to reduce the social, community and health-related harms of illicit drug use by injection drug users (IDUs). There are, however, few data on the benefits of such enforcement or on the potential harms. A large-scale police “crackdown” to control illicit drug use in Vancouvers Downtown Eastside provided us with an opportunity to evaluate the effect. Methods: As part of our ongoing prospective cohort study of IDUs in Vancouver, we examined data collected from 244 IDUs in the 3 months before the police crackdown and from 142 IDUs in the 3 months after the start of the crackdown, on Apr. 7, 2003. All study subjects were active drug users. We also examined external data on needle exchanges and syringe disposal. Results: The 2 groups of IDUs were statistically similar: they were mainly young (mean age 39 years) and male (63%), and they had injected illicit drugs for 13 years on average. Ethnic background and the proportion homeless were also similar. There were no statistically significant reported differences (all p > 0.1) in the street price of heroin, cocaine or “crack” in the 2 periods. In the 3-month periods before and after the crackdown, respectively, the rates of daily heroin injection were 27.9% and 26.8%, daily cocaine injection 28.7% and 27.5%, and daily crack use 59.4% and 60.6% (all p > 0.1). The proportions of study subjects receiving methadone treatment, 41.0% and 44.4% (p = 0.516), did not differ. However, the proportions reporting a change in where drugs were used, 22.5% and 33.8% (p < 0.05), and the proportions reporting a change in the neighbourhood of use because of police presence, 18.1% and 26.8% (p < 0.05), increased significantly. Needle-exchange data confirmed that the community levels of drug use were unchanged. Disposal statistics demonstrated that the monthly average number of used syringes found on the streets outside the traditional area of drug use increased from 784 in the 3 months before Apr. 1 to 1253 in the subsequent 3 months (p = 0.002) and the monthly average number of used syringes found in public boxes for the safe disposal of syringes decreased from 865 to 502 (p = 0.018). Interpretation: The effort to control illicit drug use did not alter the price of drugs or the frequency of use, nor did it encourage enrolment in methadone treatment programs. Several measures indicated displacement of injection drug use from the area of the crackdown into adjacent areas of the city, which has implications for both recruitment of new initiates into injection drug use and HIV prevention efforts.

Impact of HIV infection on mortality in a cohort of injection drug users.

&NA; The prevalence of HIV has been rising among injection drug users (IDUs) and AIDS is now an important cause of death among that population. We tracked mortality and recorded detailed causes of death in the Vancouver Injection Drug Users Study (VIDUS). This is an open cohort of over 1,400 active IDUs that began in May 1996. At enrollment and at semiannual follow‐up visits, a trained interviewer administers a detailed semistructured questionnaire. Mortality was recorded during follow‐up and detailed causes of death were collected from coroners reports, hospital records, and the provincial (British Columbia) registry. Causes of death were obtained on 125 participants. Overall, the leading cause of death was overdose accounting for 25% of deaths among HIV‐positive participants and 42% among HIV‐negative participants. Of the 65 deaths among HIV‐positive individuals, 22 (34%) were HIV related. Mortality was associated with older age (adjusted hazards ratio [AHR], 1.03 per year), HIV positivity (AHR, 2.67), injection cocaine use (AHR, 2.23) and methadone treatment (AHR, 0.47). The high rate of HIV in this population has added significantly to the burden of illness and death in this marginalized population.