The delivery of antiretroviral therapy (ART) to injection drug users (IDU) may be influenced by provider concerns regarding the potential for increased HIV-related risk behavior following the initiation of HIV treatment. We evaluated whether ART initiation was associated with changes in syringe lending patterns among a long-term prospective cohort of HIV-positive IDU in Vancouver, Canada. Among 380 ART-naïve individuals eligible for this analysis, the median age was 34.2 (interquartile range [IQR] 27.7 – 40.8), 171 (45.0%) were female, and the median follow-up duration was 60 months (IQR = 18 – 113). Between May 1996 and April 2008, 260 (68.4%) participants initiated ART. In a generalized linear mixed-effects model which compared each individual’s likelihood of sharing syringes prior to and following the initiation of ART, syringe lending was not significantly associated with ART initiation in unadjusted (odds ratio = 0.72, 95% CI: 0.38 – 1.36) or adjusted (odds ratio = 0.78, 95% CI: 0.42 – 1.45) analyses. Concerns regarding increased injection risk behaviors following the initiation of ART were not observed in this setting.
injection drug use; antiretroviral therapy; syringe lending; HIV
To model the effect of adherence and duration of viral suppression on the risk of viral rebound.
Viral rebound was defined as the first of at least 2 consecutive viral loads >400 copies/mL following initial viral suppression. The main exposures were adherence, presence of ARV class resistance before rebound or censoring date, and the percentage of follow-up time with viral suppression.
A total of 274 (N=1305; 21%) individuals experienced viral rebound. Median time of suppression before rebound was 2 years. Viral rebound was less likely to occur among those with longer duration of continuous viral suppression (odds ratio 0.37; 95% confidence interval [CI] 0.32-0.42). Among individuals with moderate levels of adherence (80%-<95%), the probability of virologic failure was 0.85 after being suppressed for 12 months and it was 0.08 after 72 months being suppressed (p-value <0.01). Individuals with drug resistance were at a higher risk of viral rebound.
The risk of viral rebound decreased with longer duration of viral suppression within each of adherence strata studied. While perfect adherence remains an important goal of therapy to prevent disease progression, individuals with long-term viral suppression may be able to miss more doses without experiencing viral rebound.
Adherence; HAART; virologic failure; viral rebound; resistance; long-term suppression
Although antiretroviral therapy (ART) dramatically reduces viral load and improves survival among HIV-infected injection drug users (IDU), several short-term studies have raised concerns that ART initiation may result in increases in sexual risk behaviour among IDU.
We used data from a long-running cohort of HIV-positive IDU to examine whether ART initiation was associated with increases in several measures of sexual risk behaviour. The date of ART initiation was determined through a validated linkage to a centralized ART dispensation pharmacy.
We used generalized linear mixed-effects modeling to examine whether sexual activity, unprotected intercourse, and multiple sexual partnerships were more likely in the 12 month period following ART initiation.
Among 457 individuals who were ART naïve at baseline, the median age was 34 (interquartile range [IQR]: 28–41) and 202 (44.2%) were female. Between May 1996 and April 2008, 260 (56.7%) participants initiated ART. In multivariate analyses, ART initiation was not associated with sexual activity (adjusted Odds Ratio [AOR] = 0.87, 95%CI: 0.60–1.25), unprotected intercourse (AOR = 0.82, 95%CI: 0.51–1.31), or multiple sexual partnerships (AOR = 0.93, 95%CI: 0.61–1.40).
In this study of HIV-positive IDU, we failed to detect an increase in sexual risk behaviour during the period following ART initiation. In light of this evidence, and given the known positive effect of ART on survival and its potential role in reducing HIV transmission, concerns regarding potential increases in sexual risk-taking should not undermine the delivery of ART to IDU.
injection drug use; antiretroviral therapy; sexual risk; HIV; AIDS
Cohort studies and mathematical models have suggested that expanded coverage with highly active antiretroviral therapy (HAART) could decrease HIV transmission. This study focuses on the HIV epidemic, stratified by injection drug use, in the province of British Columbia, Canada, and seeks to estimate the association between plasma HIV-1-viral load, HAART coverage and number of new cases of HIV at the population-level.
HAART use, plasma HIV-1-viral level determinations, and rates of reportable sexually transmitted infections, including HIV, are all recorded in province-wide registries allowing for temporal comparisons of these parameters. Trends of new HIV positive tests and number of individuals on HAART were modeled using generalized additive models. Poisson log-linear regression models were used to estimate the association between the outcome new HIV positive tests (per 100 population) and the covariates viral load (log10 transformed), year, and number of individuals on HAART.
Our results demonstrate a strong association at the population-level between increasing levels of HAART coverage, decreased viral load and decreased new HIV diagnoses/year, against a background of increased HIV testing and increased rates of other STIs in the province. Our results support the proposed secondary benefit of HAART, used within current medical guidelines, on HIV transmission at a population level.
Using multivariate logistic regression, we examined the prevalence and correlates of homelessness among youth enrolled in a community-recruited prospective cohort known as the At-Risk Youth Study (ARYS), between September 2005 and October 2006. Of 478 individuals included in this analysis, 132 (27.6%) were female and 120 (25.1%) self-identified as Aboriginal. The median age was 22 (IQR: 20–24). In total, 284 (56.9%) participants reported baseline homelessness, with most living either at no fixed address, on the street, or in a hostel or shelter. Factors associated with homelessness included public injecting, frequent crack use, experienced violence, having less than a high-school education, and not having been in any addiction treatment. Homeless individuals were at-risk for various adverse health outcomes. These findings indicate the need for additional interventions, including residential addiction treatment, to address homelessness and drug use among youth.
Homelessness; youth; drug use; risk behavior
VprR77Q has been associated with long-term nonprogressive (LTNP) HIV infection. We wished to investigate the prevalence, clinical correlates, and effect on treatment response of VprR77Q in a cohort of antiretroviral-naïve individuals initiating Highly Active Antiretroviral Therapy (HAART). Baseline plasma samples from 728 subjects were genotyped using RT-PCR and direct DNA sequencing. Cox proportional hazards regression was used to model the effects of VprR77Q on virologic and immunologic responses, and survival following initiation of HAART, over a median 4.5 years follow-up. We found that 308 subjects (42.3%) harbored VprR77Q alone or in combination with another amino acid, while 420 (57.7%) harbored an amino acid other than Q. A cross-sectional analysis found no correlation between R77Q and baseline plasma viral load (pVL), CD4 count, diagnosis of AIDS, or sociodemographic characteristics including age, gender and history of injection drug use (p > 0.1). In multivariate analyses, no significant associations between VprR77Q and initial pVL and CD4 responses to HAART (p > 0.1) or survival following initiation of treatment were observed. The high prevalence and the lack of association with pre-therapy clinical parameters in this cohort argue against an association of R77Q with LTNP status. These results do not support an association between R77Q and HAART response.
HIV; Vpr; R77Q; antiretroviral therapy response; HOMER cohort
This paper examines the ethical probity of Health Canada’s Special Access Program (SAP). The SAP is designed for patients with life-threatening conditions who require “emergency” access to drugs that are not authorized for use in Canada when conventional therapies have failed. We argue that the SAP inappropriately uses the tenets of evidence-based decision-making in situations where evidence-based decision-making is unfeasible. The SAP should abandon its pretence of evidence-based decision-making and adopt a transparent process in which the values guiding decisions are explicit and corrigible. We recommend the ethical principles of autonomy, non-maleficence, beneficence and justice.
We examined the effect of hepatitis C virus (HCV) seropositivity on risk of death among people receiving their first antiretroviral treatment (ART) for HIV infection.
In British Columbia, the HIV/ AIDS Drug Treatment Program is the only source of free ART. Patients who initiated a triple-drug ART regimen between July 31, 1996, and July 31, 2000, were included if they were ART-naive and had baseline HCV serological data. Outcomes of interest for survival analysis were deaths from natural and HIV-related causes, with a data cutoff of June 30, 2003.
Of 1186 eligible subjects, 606 (51%) were HCV positive and 580, negative. Fewer HCV-positive people were male (78% v. 93%, p < 0.001) and had an AIDS diagnosis at baseline (11% v. 15%, p = 0.028). Their CD4 fraction was significantly higher at baseline (19% v. 16% of T lymphocytes, p < 0.001) but their absolute CD4 counts, log HIV viral load and the type of ART initiated were similar to those of HCV negative people. Of 163 deaths (from natural causes only) during the study period, 118 (19%) were in HCV positive and 45 (8%) in HCV negative patients (p < 0.001); of the 114 deaths attributed to HIV infection, these proportions were 79 (13%) versus 35 (6%; p < 0.001). After adjustment for potential confounders, HCV seropositivity remained predictive of death (adjusted hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.50– 3.21, p < 0.001), especially HIV-related death (adjusted HR 1.75, 95% CI 1.13– 2.72, p = 0.012).
In this population-based HIV treatment program, we found HCV seropositivity to be an independent predictor of mortality, especially death related to HIV infection.
North America's first medically supervised safer injecting facility for illicit injection drug users was opened in Vancouver on Sept. 22, 2003. Although similar facilities exist in a number of European cities and in Sydney, Australia, no standardized evaluations of their impact have been presented in the scientific literature.
Using a standardized prospective data collection protocol, we measured injection-related public order problems during the 6 weeks before and the 12 weeks after the opening of the safer injecting facility in Vancouver. We measured changes in the number of drug users injecting in public, publicly discarded syringes and injection-related litter. We used Poisson log-linear regression models to evaluate changes in these public order indicators while considering potential confounding variables such as police presence and rainfall.
In stratified linear regression models, the 12-week period after the facility's opening was independently associated with reductions in the number of drug users injecting in public (p < 0.001), publicly discarded syringes (p < 0.001) and injection-related litter (p < 0.001). The predicted mean daily number of drug users injecting in public was 4.3 (95% confidence interval [CI] 3.5–5.4) during the period before the facility's opening and 2.4 (95% CI 1.9–3.0) after the opening; the corresponding predicted mean daily numbers of publicly discarded syringes were 11.5 (95% CI 10.0–13.2) and 5.4 (95% CI 4.7–6.2). Externally compiled statistics from the city of Vancouver on the number of syringes discarded in outdoor safe disposal boxes were consistent with our findings.
The opening of the safer injecting facility was independently associated with improvements in several measures of public order, including reduced public injection drug use and public syringe disposal.
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 Vancouver's Downtown Eastside provided us with an opportunity to evaluate the effect.
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.
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).
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.
LONG-TERM REMISSION OF HIV-1 DISEASE CAN BE READILY ACHIEVED by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.
The benefits of highly active antiretroviral therapy (HAART) for the treatment of HIV infection are well documented, but concerns regarding access and adherence to HAART are growing. We evaluated virological responses to HAART among HIV-1 infected patients who were injection drug users (IDUs) in a population-based setting where HIV/AIDS care is delivered free of charge.
We evaluated previously untreated HIV-1 infected men and women who initiated HAART between Aug. 1, 1996, and July 31, 2000, and who were followed until Mar. 31, 2002, in a province-wide HIV treatment program. We used Kaplan–Meier methods and Cox proportional hazards regression in our evaluation of time to suppression (i.e., less than 500 copies/mL) and rebound (i.e., 500 copies/mL or more) of plasma HIV-1 RNA, with patients stratified according to whether or not they had a history of injection drug use.
Overall, 1422 patients initiated HAART during the study period, of whom 359 (25.2%) were IDUs. In Kaplan–Meier analyses, the cumulative suppression rate at 12 months after initiation of HAART was 70.8% for non-IDUs and 51.4% for IDUs (p < 0.001) (these values include people who achieved suppression before 12 months but who might not have been followed for the full 12-month period). Among patients who achieved suppression of plasma HIV-1 RNA, the cumulative rebound rate at 12 months after initial suppression was 23.8% for non-IDUs and 34.7% for IDUs (p < 0.001). However, after adjustment for adherence and other covariates, the rates of HIV-1 RNA suppression (adjusted relative hazard 0.9, 95% confidence interval [CI] 0.7–1.0) and HIV-1 RNA rebound (adjusted relative hazard 1.3, 95% CI 1.0–1.6) were similar between non-IDUs and IDUs. Differences between non-IDUs and IDUs were even less pronounced in subanalyses that considered only therapy-adherent patients (p > 0.1).
Non-IDUs and IDUs had similar rates of HIV-1 RNA suppression and rebound after the initiation of HAART, once lower levels of adherence were taken into account. Nevertheless, the lower virological response rates among IDUs suggest that, unless interventions are undertaken to improve adherence, these patients may experience elevated rates of disease progression and use of medical services in our setting.
More than 93% of the nearly $500 million spent annually on Canada's drug strategy goes toward efforts to reduce the illicit drug supply. However, little is known about the effectiveness of this strategy. On Sept. 2, 2000, Canadian police seized approximately 100 kg of heroin in one of the nation's largest-ever seizures of this drug. An ongoing prospective cohort study of injection drug users afforded an opportunity to evaluate the impact of this seizure.
The Vancouver Injection Drug User Study is a prospective cohort study of injection drug users that began in 1996. The present study relied primarily on data acquired from participants who were seen during the 30-day periods immediately before and after the seizure. We compared drug use and behavioural characteristics, heroin and cocaine prices, and participants' reports of whether law enforcement had affected their source of drugs or the types of drugs available on the street, as well as overdoses, in these 2 periods.
The 138 participants seen before the seizure were similar to the 123 participants seen after the seizure with respect to age, sex, ethnic background, education, HIV serostatus, neighbourhood residence, instability of housing, employment status, use of methadone maintenance therapy and all other measured potential confounders (all p > 0.10). We found no difference in the extent to which participants in the 2 groups reported daily use of heroin, frequency of nonfatal overdoses, or whether law enforcement had affected their source of drugs or the types of drugs available on the street (all p > 0.10). Although we detected no difference in the price of cocaine, the median reported price of heroin went down after the seizure (p = 0.034), which suggests that other shipments compensated for the seizure. External evaluations of deaths from overdoses and heroin purity indicated that the seizure had no impact, nor was any impact seen when the periods of analysis were extended.
The massive heroin seizure appeared to have no measurable public health benefit. Closer scrutiny of enforcement efforts is warranted to ensure that resources are delivered to the most efficient and cost-effective public health programs.
In several European countries safer injecting rooms have reduced the public disorder and health-related problems of injection drug use. We explored factors associated with needle-sharing practices that could potentially be alleviated by the availability of safer injecting rooms in Canada.
The Vancouver Injection Drug User Study is a prospective cohort study of injection drug users (IDUs) that began in 1996. The analyses reported here were restricted to the 776 participants who reported actively injecting drugs in the 6 months before the most recent follow-up visit, during the period January 1999 to October 2000. Needle sharing was defined as either borrowing or lending a used needle in the 6-month period before the interview.
Overall, 214 (27.6%) of the participants reported sharing needles during the 6 months before follow-up; 106 (13.7%) injected drugs in public, and 581 (74.9%) reported injecting alone at least once. Variables independently associated with needle sharing in a multivariate analysis included difficulty getting sterile needles (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.8–4.1), requiring help to inject drugs (adjusted OR 2.0, 95% CI 1.4–2.8), needle reuse (adjusted OR 1.8, 95% CI 1.3–2.6), frequent cocaine injection (adjusted OR 1.6, 95% CI 1.1–2.3) and frequent heroin injection (adjusted OR 1.5, 95% CI 1.04–2.1). Conversely, HIV-positive participants were less likely to share needles (adjusted OR 0.5, 95% CI 0.4–0.8), although 20.2% of the HIV-positive IDUs still reported sharing needles.
Despite the availability of a large needle-exchange program and targeted law enforcement efforts in Vancouver, needle sharing remains an alarmingly common practice in our cohort. We identified a number of risk behaviours — difficulty getting sterile needles, needle sharing and reuse, injection of drugs in public and injecting alone (one of the main contributing causes of overdose) — that may be alleviated by the establishment of supervised safer injecting rooms.
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 confirmed cases (those with records in the CfE, CDC and MoH databases) positively identified by each algorithm. A priori hypotheses were generated and tested to verify excluded cases.
A total of 25,673 individuals were identified as having at least one HIV-related health record. Among 9,454 unconfirmed cases, the selected case-finding algorithm identified 849 individuals believed to be HIV-positive. The sensitivity of this algorithm among confirmed cases was 88%. Those excluded from the cohort were more likely to be female (44.4% vs. 22.5%; p<0.01), had a lower mortality rate (2.18 per 100 person years (100PY) vs. 3.14/100PY; p<0.01), and had lower median rates of health service utilization (days of medications dispensed: 9745/100PY vs. 10266/100PY; p<0.01; days of inpatient care: 29/100PY vs. 98/100PY; p<0.01; physician billings: 602/100PY vs. 2,056/100PY; p<0.01).
The application of validated case-finding algorithms and subsequent hypothesis testing provided a strong framework for defining a population-level cohort of HIV infected people in BC using administrative databases.
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 in the three provinces (4 fold increase). BC was the only province with a statistically significant decrease (trend test p<0.0001) in the rate of new HIV diagnoses from 18.05 to 7.94 new diagnoses per 100,000 population. Our analysis showed that for each 10% increment in HAART coverage the rate of new HIV diagnoses decreased by 8% (95% CI: 2.4%, 13.3%)
Except for British Columbia, the number of new HIV diagnoses per year has remained relatively stable across Canada over the study period. The decline in the rate of new HIV diagnoses per year may be in part attributed to the greater expansion of HAART coverage in this province.
Background. HIV-infected women are disproportionately burdened by gynaecological complications, psychological disorders, and certain sexually transmitted infections that may not be adequately addressed by HIV-specific care. We estimate the prevalence and covariates of women's health care (WHC) utilization among harder-to-reach, treatment-experienced HIV-infected women in British Columbia (BC), Canada. Methods. We used survey data from 231 HIV-infected, treatment-experienced women enrolled in the Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) study, which recruited harder-to-reach populations, including aboriginal people and individuals using injection drugs. Independent covariates of interest included sociodemographic, psychosocial, behavioural, individual health status, structural factors, and HIV clinical variables. Logistic regression was used to generate adjusted estimates of associations between use of WHC and covariates of interest.
Results. Overall, 77% of women reported regularly utilizing WHC. WHC utilization varied significantly by region of residence (P value <0.01). In addition, women with lower annual income (AOR (95% CI) = 0.14 (0.04–0.54)), who used illicit drugs (AOR (95% CI) = 0.42 (0.19–0.92)) and who had lower provider trust (AOR (95% CI) = 0.97 (0.95–0.99)), were significantly less likely to report using WHC. Conclusion. A health service gap exists along geographical and social axes for harder-to-reach HIV-infected women in BC. Women-centered WHC and HIV-specific care should be streamlined and integrated to better address women's holistic health.
We developed and validated a new and simple metric, the Programmatic Compliance Score (PCS), based on the IAS-USA antiretroviral therapy management guidelines for HIV-infected adults, as a predictor of all-cause mortality, at a program-wide level. We hypothesized that non-compliance would be associated with the highest probability of mortality.
Methods and Findings
3543 antiretroviral-naive HIV-infected patients aged ≥19 years who initiated antiretroviral therapy between January 1, 2000 and August 31, 2009 in British Columbia (BC), Canada, were followed until August 31, 2010. The PCS is composed by six non-performance indicators based on the IAS-USA guidelines: (1) having <3 CD4 count tests in the first year after starting antiretroviral therapy; (2) having <3 plasma viral load tests in the first year after starting antiretroviral therapy; (3) not having drug resistance testing done prior to starting antiretroviral therapy; (4) starting on a non-recommended antiretroviral therapy regimen; (5) starting therapy with CD4 <200 cells/mm3; and (6) not achieving viral suppression within 6 months since antiretroviral therapy initiation. The sum of these six indicators was used to develop the PCS score - higher score indicates poorer performance. The main outcome was all-cause mortality. Each PCS component was independently associated with mortality. In the mortality analysis, the odds ratio (OR) for PCS ≥4 versus 0 was 22.37 (95% CI 10.46–47.84).
PCS was strongly associated with all-cause mortality. These results lend independent validation to the IAS-USA treatment guidelines for HIV-infected adults. Further efforts are warranted to enhance the PCS as a means to further improve clinical outcomes. These should be specifically evaluated and targeted at healthcare providers and patients.
The lower limit of detection of the original Roche Amplicor HIV plasma viral load (pVL) assay (50 copies/mL) has defined HIV treatment success. The Amplicor assay, however, has been replaced by the Roche TaqMan assay(s). Changes to the limits of detection and calibration have not been validated for clinical utility. Sudden increases in the number of patients with detectable pVL have been reported following the introduction of the TaqMan version 1 assay.
Between October 2009 and April 2010 all routine pVL samples from British Columbia, Canada, with 40–250 copies/mL by TaqMan were re-tested by Amplicor (N = 1198). Subsequent short-term virological and resistance outcomes were followed in patients with unchanged therapy (N = 279; median 3.2 months follow-up).
TaqMan and Amplicor values correlated poorly at low pVL values. Low-level pVL by TaqMan was not associated with impending short-term virological failure; only 17% of patients with 40–250 copies/mL by TaqMan had detectable pVL by Amplicor at follow-up. During the follow-up period only 20% of patients had an increase in pVL by TaqMan (median [IQR]: 80 [36–283] copies/mL). In addition, in ∼2.4% of samples pVL was dramatically underestimated by TaqMan due to poor binding of the proprietary TaqMan primers.
The replacement of Amplicor with the TaqMan assay has altered the previously accepted definition of HIV treatment failure without any evidence to support the clinical relevance of the new definition. Given the systematic differences in measurement in the low pVL range the British Columbia HIV treatment guidelines now use a threshold of >250 copies/mL by TaqMan to define treatment failure.
To establish the reliability and validity of a shortened (10-item) depression scale used among HIV-positive patients enrolled in the Drug Treatment Program in British Columbia, Canada.
The 10-item CES-D (Center for Epidemiologic Studies Depression Scale) was examined among 563 participants who initiated antiretroviral therapy (ART) between August 1, 1996 and June 30, 2002. Internal consistency of the scale was measured by Cronbach’s alpha. Using the original CES-D 20 as primary criteria, comparisons were made using the Kappa statistic. Predictive accuracy of CES-D 10 was assessed by calculating sensitivity, specificity, positive predictive values and negative predictive values. Factor analysis was also performed to determine if the CES-D 10 contained the same factors of positive and negative affect found in the original development of the CES-D.
The correlation between the original and the shortened scale is very high (Spearman correlation coefficient = 0.97 (P<0.001). Internal consistency reliability coefficients of the CES-D 10 were satisfactory (Cronbach α = 0.88). The CES-D 10 showed comparable accuracy to the original CES-D 20 in classifying participants with depressive symptoms (Kappa = 0.82, P<0.001). Sensitivity of CES-D 10 was 91%; specificity was 92%; and positive predictive value was 92%. Factor analysis demonstrates that CES-D 10 contains the same underlying factors of positive and negative affect found in the original development of the CES-D 20.
The 10-item CES-D is a comparable tool to measure depressive symptoms among HIV-positive research participants.
The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 109/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 109/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed.
Bohdan Nosyk and Julio Montaner argue that the cost-effectiveness of HAART roll out has been significantly underestimated because economic analyses haven't yet taken into account the beneficial impact of HAART on HIV transmission.