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Background:Co-prescribing benzodiazepines and opioids is relatively contraindicated due to the possible overdose risk. However, people living with HIV (PLWH) may have concurrent psychiatric and/or chronic pain diagnoses that may lead to the use of opioids and/or benzodiazepines for symptomatic treatment. Consequently, some PLWH may be at-risk for the health harms associated with the co-prescribing of these medications. Given this, the objectives of this study were to first examine the prevalence of opioids and benzodiazepines co-prescribing, and second, to characterize patient factors associated with the co-prescribing of opioids and benzodiazepines among PLWH in British Columbia (BC), Canada. Methods:Using data derived from a longitudinal BC cohort, we used bivariable and multivariable generalized estimating equation models to establish the prevalence of a benzodiazepine and opioid co-prescription and determine factors associated with this practice. Results:Between 1996 and 2015, 14 484 PLWH were included in the study and were followed for the entire study period. At baseline, 548 people (4%) were co-prescribed opioids and benzodiazepines, 6593 (46%) were prescribed opioids only, 2887 (20%) were prescribed benzodiazepines only, and 4456 (31%) were prescribed neither medication. A total of 3835 (27%) participants were prescribed both medications at least once during the study period. Factors positively associated with concurrent opioid and benzodiazepine prescribing included: depression/mood disorder [adjusted odds ratio (AOR) = 1.32; 95% confidence interval (CI) = 1.22–1.43] and anxiety disorder (AOR = 1.45; 95% CI = 1.27–1.66), whereas female sex (AOR = 0.76; 95% CI = 0.64-0.91) and substance use disorder (SUD) (AOR = 0.82; 95% CI = 0.74–0.90) were negatively associated with the outcome. Conclusion:Our findings indicate that co-prescription of opioids and benzodiazepines was seen at some point during study follow-up in over a quarter of PLWH. Given the known risks associated with this prescribing practice, future research can focus on the outcomes of co-prescribing among this patient population and the development of strategies to reduce the co-prescribing of opioids and benzodiazepines.

Summary Background The HIV epidemic in the USA is a collection of diverse local microepidemics. We aimed to identify optimal combination implementation strategies of evidence-based interventions to reach 90% reduction of incidence in 10 years, in six US cities that comprise 24·1% of people living with HIV in the USA. Methods In this economic modelling study, we used a dynamic HIV transmission model calibrated with the best available evidence on epidemiological and structural conditions for six US cities: Atlanta (GA), Baltimore (MD), Los Angeles (CA), Miami (FL), New York City (NY), and Seattle (WA). We assessed 23 040 combinations of 16 evidence-based interventions (ie, HIV prevention, testing, treatment, engagement, and re-engagement) to identify combination strategies providing the greatest health benefit while remaining cost-effective. Main outcomes included averted HIV infections, quality-adjusted life-years (QALYs), total cost (in 2018 US$), and incremental cost-effectiveness ratio (ICER; from the health-care sector perspective, 3% annual discount rate). Interventions were implemented at previously documented and ideal (90% coverage or adoption) scale-up, and sustained from 2020 to 2030, with outcomes evaluated until 2040. Findings Optimal combination strategies providing health benefit and cost-effectiveness contained between nine (Seattle) and 13 (Miami) individual interventions. If implemented at previously documented scale-up, these strategies could reduce incidence by between 30·7% (95% credible interval 19·1–43·7; Seattle) and 50·1% (41·5–58·0; New York City) by 2030, at ICERs ranging from cost-saving in Atlanta, Baltimore, and Miami, to $95 416 per QALY in Seattle. Incidence reductions reached between 39·5% (26·3–53·8) in Seattle and 83·6% (70·8–87·0) in Baltimore at ideal implementation. Total costs of implementing strategies across the cities at previously documented scale-up reached $559 million per year in 2024; however, costs were offset by long-term reductions in new infections and delayed disease progression, with Atlanta, Baltimore, and Miami projecting cost savings over the 20 year study period. Interpretation Evidence-based interventions can deliver substantial public health and economic value; however, complementary strategies to overcome social and structural barriers to HIV care will be required to reach national targets of the ending the HIV epidemic initiative by 2030. Funding National Institutes of Health.

Objectives Optimizing antiretroviral drug combination on an individual basis can be challenging, particularly in settings with limited access to drugs and genotypic resistance testing. Here we describe our latest computational models to predict treatment responses, with or without a genotype, and compare their predictive accuracy with that of genotyping. Methods Random forest models were trained to predict the probability of virological response to a new therapy introduced following virological failure using up to 50 000 treatment change episodes (TCEs) without a genotype and 18 000 TCEs including genotypes. Independent data sets were used to evaluate the models. This study tested the effects on model accuracy of relaxing the baseline data timing windows, the use of a new filter to exclude probable non-adherent cases and the addition of maraviroc, tipranavir and elvitegravir to the system. Results The no-genotype models achieved area under the receiver operator characteristic curve (AUC) values of 0.82 and 0.81 using the standard and relaxed baseline data windows, respectively. The genotype models achieved AUC values of 0.86 with the new non-adherence filter and 0.84 without. Both sets of models were significantly more accurate than genotyping with rules-based interpretation, which achieved AUC values of only 0.55–0.63, and were marginally more accurate than previous models. The models were able to identify alternative regimens that were predicted to be effective for the vast majority of cases in which the new regimen prescribed in the clinic failed. Conclusions These latest global models predict treatment responses accurately even without a genotype and have the potential to help optimize therapy, particularly in resource-limited settings.

The L1 gene encodes for the major capsid protein of human papillomaviruses (HPV). There is limited information on the polymorphism of L1 for types related to HPV-16. This report explores the polymorphism of L1 in phylogenetically related types 31, 33, and 35 compared to HPV-16. Genital specimens collected from 732 HIV-seropositive and 323 HIV-seronegative women were screened for HPV DNA with consensus L1 PCR. Cervical samples positive for HPV-16 (n = 74), HPV-31 (n = 78), HPV-33 (n = 37), and HPV-35 (n = 58) were further characterized by PCR-sequencing of the complete L1 gene. The number of nucleotide substitutions within L1 ranged from 19 for HPV-33 to 52 for HPV-31. The ratio of the number of variants/number of isolates tested was higher for HPV-31 (56.4%, P = 0.05) and HPV-35 (60.3%, P = 0.04) compared to HPV-16 (40.5%), while this ratio was lower for HPV-33 (24.3%), although not significantly (P = 0.14). The maximal distance between HPV variants was greater in the five putative surface-exposed loops of L1 than in sequences outside the loops (P

In human immunodeficiency virus–hepatitis C-coinfected, both protease inhibitor- and nonnucleoside reverse transcriptase inhibitor-based regimens were associated with progression of liver fibrosis over time when paired with a backbone of abacavir/lamivudine but not tenofovir/emtricitabine., Background. Liver diseases progress faster in human immunodeficiency virus (HIV)–hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV–coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). Methods. Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction–positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent. Results. A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, −3%, 19%) or NNRTI users (3% per 5 years, 95% CI, −7%, 12%). Conclusions. Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV–coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used.

To determine the relationship between methadone maintenance therapy (MMT) and hepatitis C (HCV) seroconversion among illicit drug users.A generalized estimating equation model assuming a binomial distribution and a logit-link function was used to examine for a possible protective effect of MMT use on HCV incidence.Data from three prospective cohort studies of illicit drug users in Vancouver, Canada between 1996 and 2012.A total of 1004 HCV antibody-negative illicit drug users stratified by exposure to MMT.Baseline and semi-annual HCV antibody testing and standardized interviewer-administered questionnaire soliciting self-reported data relating to drug use patterns, risk behaviors, detailed socio-demographic data and status of active participation in an MMT program.One hundred and eighty-four HCV seroconversions were observed for an HCV incidence density of 6.32 [95% confidence interval (CI) = 5.44-7.31] per 100 person-years. After adjusting for potential confounders, MMT exposure was protective against HCV seroconversion [adjusted odds ratio (AOR) = 0.47; 95% CI = 0.29-0.76]. In subanalyses, a dose-response protective effect of increasing MMT exposure on HCV incidence (AOR = 0.87; 95% CI = 0.78-0.97) per increasing 6-month period exposed to MMT was observed.Participation in methadone maintenance treatment appears to be highly protective against hepatitis C incidence among illicit drug users. There appears to be a dose-response protective effect of increasing methadone exposure on hepatitis C incidence.

Objectives: The optimal individualized selection of antiretroviral drugs in resource-limited settings is challenging because of the limited availability of drugs and genotyping. Here we describe the development of the latest computational models to predict the response to combination antiretroviral therapy without a genotype, for potential use in such settings. Methods: Random forest models were trained to predict the probability of a virological response to therapy (

Childhood emotional abuse is a known risk factor for various poor social and health outcomes. While people who inject drugs (IDU) report high levels of violence, in addition to high rates of childhood maltreatment, the relationship between childhood emotional abuse and later life violence within this population has not been examined.Cross-sectional data were derived from an open prospective cohort of IDU in Vancouver, Canada. Childhood emotional abuse was measured using the Childhood Trauma Questionnaire. We used multivariate logistic regression to examine potential associations between childhood emotional abuse and being a recent victim or perpetrator of violence.Between December 2005 and May 2013, 1437 IDU were eligible for inclusion in this analysis, including 465 (32.4%) women. In total, 689 (48.0%) reported moderate to severe history of childhood emotional abuse, whereas 333 (23.2%) reported being a recent victim of violence and 173 (12.0%) reported being a recent perpetrator of violence. In multivariate analysis, being a victim of violence (adjusted odds ratio = 1.49, 95% confidence interval 1.15-1.94) and being a perpetrator of violence (adjusted odds ratio = 1.58, 95% confidence interval 1.12-2.24) remained independently associated with childhood emotional abuse.We found high rates of childhood emotional abuse and subsequent adult violence among this sample of IDU. Emotional abuse was associated with both victimisation and perpetration of violence. These findings highlight the need for policies and programmes that address both child abuse and historical emotional abuse among adult IDU.

Crack pipe sharing is a risky practice that has been associated with the transmission of hepatitis C and other harms. While previous research has exclusively focused on this phenomenon among adults, this study examines crack pipe sharing among street-involved youth.From May 2006 to May 2012, data were collected from the At-Risk Youth Study, a cohort of street-involved youth aged 14-26 in Vancouver, Canada. Survey data from active crack smokers were analysed using generalised estimating equations logistic regression.Over the study period, 567 youth reported smoking crack cocaine and contributed 1288 observations, among which 961 (75%) included a report of crack pipe sharing. In multivariate analysis, factors that were associated with crack pipe sharing included difficulty accessing crack pipes [adjusted odds ratio (AOR) = 1.58, 95% confidence interval (CI) 1.13-2.20]; homelessness (AOR = 1.87, 95% CI 1.43-2.44); regular employment (AOR = 1.53, 95% CI 1.15-2.04); daily non-injection crystal methamphetamine use (AOR = 2.04, 95% CI 1.11-3.75); daily crack smoking (AOR = 1.37, 95% CI 1.01-1.85); encounters with the police (AOR = 1.42, 95% CI 1.01-1.99); and reporting unprotected sex (AOR = 1.95, 95% CI 1.47-2.58).The prevalence of crack pipe sharing was high among our sample and independently associated with structural factors including difficulty accessing crack pipes and homelessness. Crack pipe sharing was also associated with high-intensity drug use and a number of other markers of risk and vulnerability. Collectively, these findings highlight opportunities for health services to better engage with this vulnerable group and reduce this risky behaviour.

Crack cocaine pipe sharing is associated with various health-related harms, including hepatitis C transmission. Although difficulty accessing crack pipes has been found to predict pipe sharing, little is known about the factors that limit pipe access in settings where pipes are provided at no cost, albeit in limited capacity. Therefore, we investigated crack pipe access among people who use drugs in Vancouver, Canada.Data were collected through two Canadian prospective cohort studies. Generalised estimating equations with logit link for binary outcomes were used to identify factors associated with difficulty accessing crack pipes.Among 914 participants who reported using crack cocaine, 33% reported difficulty accessing crack pipes. In multivariate analyses, factors independently associated with difficulty accessing crack pipes included: sex work involvement [adjusted odds ratio (AOR) = 1.57; 95% confidence interval (CI): 1.03-2.39], having shared a crack pipe (AOR = 1.69; 95% CI: 1.32-2.16), police presence where one buys/uses drugs (AOR = 1.47; 95% CI: 1.10-1.95), difficulty accessing services (AOR = 1.74; 95% CI: 1.31-2.32) and health problems associated with crack use (AOR = 1.37; 95% CI: 1.04-1.79). Reasons given for difficulty accessing pipes included sources being closed (48.2%) and no one around selling pipes (18.1%).A substantial proportion of people who smoke crack cocaine report difficulty accessing crack pipes in a setting where pipes are available at no cost but in limited quantity. These findings indicate the need for enhanced efforts to distribute crack pipes and address barriers to pipe access.

To determine the total burden of illicit drug overdose mortality over the study period in the province of British Columbia and investigate possible population-level determinants by estimating rates among subgroups including First Nations individuals.Review of coroner case files.The province of British Columbia, Canada.Individuals dying from an illicit drug overdose between 2001 and 2005.Age-adjusted mortality rates, standardized mortality ratios (SMR) and years of potential life lost (YPLL), stratified by major population groups.Over the study period, 909 individuals died from illicit drug overdoses, including 104 (11.4%) First Nations individuals. Compared to the general population, First Nations males and females suffered from substantially elevated SMR and YPLL. In a multivariate logistic regression analysis, First Nations deaths were significantly more likely to be among women, related to injection drug use and to have occurred in the Downtown Eastside area of Vancouver, the local epicentre of human immunodeficiency virus infection and open drug use (all P0.05).This report found highly elevated overdose death rates and levels of premature mortality among First Nations Canadians in British Columbia compared to the general population. While previously unidentified, these findings are consistent with the poorer population health profile of First Nations Canadians. Although further research is needed to identify the causes of the elevated death rates, our findings support increased availability of evidence-based overdose prevention measures.

Crack cocaine use among illicit drug users is associated with a range of health and community harms. However, long-term epidemiological data documenting patterns and risk factors for crack use initiation remain limited especially among injection drug users. We investigated longitudinal patterns of crack cocaine use among polydrug users in Vancouver, Canada.We examined the rate of crack use among injection drug users enrolled in a prospective cohort study in Vancouver, Canada between 1996 and 2005. We also used a Cox proportional hazards regression analysis to identify independent predictors of crack use initiation among this population.In total, 1603 injection drug users were recruited between May 1996 and December 2005. At baseline, 7.4% of participants reported ever using crack and this rate increased to 42.6% by the end of the study period (Mantel trend test P0.001). Independent predictors of crack use initiation during the study period included frequent cocaine injection, crystal methamphetamine injection, residency in the city's drug using epicenter and involvement in the sex trade (all P0.05).These findings demonstrate a massive increase in crack use among injection drug users in a Canadian setting. Our findings also highlight the complex interactions that contribute to the initiation of crack use among injection drug users and suggest that evidence-based interventions are urgently needed to address crack use initiation and to address harms associated with its ongoing use.

To compare the efficacy of efavirenz (EFV) vs lopinavir/ritonavir (LPV/r) in combination with azidothymidine/lamivudine in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4 counts200/mm.Prospective, randomized, open label, multicenter trial in Mexico. HIV-infected subjects with CD4200/mm were randomized to receive open label EFV or LPV/r plus azidothymidine/lamivudine (fixed-dose combination) for 48 weeks. Randomization was stratified by baseline CD4 cell count (or =100 or100/mm). The primary endpoint was the percentage of patients with plasma HIV-1 RNA50 copies/mL at 48 weeks by intention-to-treat analysis.A total of 189 patients (85% men) were randomized to receive EFV (95) or LPV/r (94). Median baseline CD4 were 64 and 52/mm, respectively (P = not significant). At week 48, by intention-to-treat analysis, 70% of EFV and 53% of LPV/r patients achieved HIV-1 RNA50 copies/mL [estimated difference 17% (95% confidence interval 3.5 to 31), P = 0.013]. The proportion with HIV-1 RNA400 copies/mL was 73% with EFV and 65% with LPV/r (P = 0.25). Virologic failure occurred in 7 patients on EFV and 17 on LPV/r. Mean CD4 count increases (cells/mm) were 234 for EFV and 239 for LPV/r. Mean change in total cholesterol and triglyceride levels were 50 and 48 mg/dL in EFV and 63 and 116 mg/dL in LPV/r (P = 0.24 and P0.01).In these very advanced HIV-infected ARV-naive subjects, EFV-based highly active antiretroviral therapy had superior virologic efficacy than LPV/r-based highly active antiretroviral therapy, with a more favorable lipid profile.

A supervised injection facility (SIF), where individuals can inject drugs under medical supervision, opened in Vancouver in 2003. The scientific evaluation of the SIF has demonstrated positive public health-related outcomes. However, the influence of supervised injection facilities on individual efforts to reintegrate into mainstream society has not been studied. We examined for a possible relationship between use of the SIF and employment among a cohort of 1090 SIF users using generalised estimating equations (GEE). In a multivariate analysis of factors associated with employment, using the SIF for > 25% of injections (versus < 25% of injections) was not statistically significant (AOR = 1.05, 95% CI: 0.88-1.27). These findings suggest that the SIF is not having an adverse impact on efforts to seek employment.

About three-quarters of the resources of Canada's Drug Strategy are directed towards enforcement-related efforts, despite a lack of scientific evidence to support this approach and little, if any, evaluation of the impacts of this investment. In this feature article, Kora deBeck, Evan Wood, Julio Montaner and Thomas Kerr report on a study that examined expenditures and activities related to the Drug Strategy as renewed in 2003. The article reviews the effectiveness of the Strategy in light of current scientific evidence pertaining to the reduction of drug-related harm. The authors find that although the Drug Strategy promised to remain accountable and regularly report its progress, information pertaining ot the evaluation of teh Strategy remains limited. Further, Canada's Drug Strategy has not seized the opportunity to promote a national standard of care that reduces the most deadly harms associated with illicit drug use. The authors conclude that from a scientific perspective, Canada's Drug Strategy should make it a priority to ensure that federal funds are directed towards cost-effective, evidence-based prevention, treatment and harm reduction services, and that these services should be available to all Canadians.