UBC Faculty Research and Publications

Incarceration is associated with used syringe lending among active injection drug users with detectable… Milloy, M-J; Kerr, Thomas; Salters, Kate; Samji, Hasina; Guillemi, Silvia; Montaner, Julio; Wood, Evan Dec 1, 2013

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
52383-12879_2013_Article_2766.pdf [ 215.78kB ]
Metadata
JSON: 52383-1.0215976.json
JSON-LD: 52383-1.0215976-ld.json
RDF/XML (Pretty): 52383-1.0215976-rdf.xml
RDF/JSON: 52383-1.0215976-rdf.json
Turtle: 52383-1.0215976-turtle.txt
N-Triples: 52383-1.0215976-rdf-ntriples.txt
Original Record: 52383-1.0215976-source.json
Full Text
52383-1.0215976-fulltext.txt
Citation
52383-1.0215976.ris

Full Text

RESEARCH ARTICLE Open AccessIncarceration is associated with used syringelending among active injection drug users withdetectable plasma HIV-1 RNA: a longitudinalanalysisM-J Milloy1,2, Thomas Kerr1,2, Kate Salters1, Hasina Samji1, Silvia Guillemi1, Julio Montaner1,2 and Evan Wood1,2*AbstractBackground: Informed by recent studies demonstrating the central role of plasma HIV-1 RNA viral load (VL) on HIVtransmission, interventions to employ HIV antiretroviral treatment as prevention (TasP) are underway. To optimizethese efforts, evidence is needed to identify factors associated with both non-suppressed VL and HIV risk behav-iours. Thus, we sought to assess the possible role played by exposure to correctional facilities on VL non-suppression and used syringe lending among HIV-seropositive people who use injection drugs (PWID).Methods: We used data from the ACCESS study, a community-recruited prospective cohort. We used longitudinalmultivariate mixed-effects analyses to estimate the relationship between incarceration and plasma HIV-1 RNA > 500copies/mL among antiretroviral therapy (ART)-exposed active PWID and, during periods of non-suppression, therelationship between incarceration and used syringe lending.Results: Between May 1996 and March 2012, 657 ART-exposed PWID were recruited. Incarceration was independentlyassociated with higher odds of VL non-suppression (Adjusted Odds Ratio [AOR] = 1.54, 95% Confidence Interval[95% CI]: 1.10, 2.16). In a separate multivariate model restricted to periods of VL non-suppression, incarceration wasindependently associated with lending used syringes (AOR = 1.81, 95% CI: 1.03, 3.18).Conclusions: The current findings demonstrate that incarceration is associated with used syringe lending amongactive PWID with detectable plasma HIV-1 RNA. Our results provide a possible pathway for the commonly observedassociation between incarceration and increased risk of HIV transmission. Our results suggest that alternatives toincarceration of non-violent PWID and evidence-based combination HIV prevention interventions for PWID withincorrectional facilities are urgently needed.BackgroundRecent studies have demonstrated that plasma HIV-1RNA viral loads (VL), at the individual, community andpopulation levels, likely play a central role in determin-ing HIV transmission dynamics. First demonstrated instudies of the role of maternal VL on the risk of peri-natal vertical transmission [1], the link between VL andthe incidence of HIV seroconversion has since been ob-served in observational analyses [2-4] and simulationmodels [5-7], and confirmed in the landmark HPTN-052randomized clinical trial [8].Informed by this insight, HIV treatment as prevention(TasP) has been adopted as a backbone of combinationHIV prevention efforts [9,10] and public health-based ef-forts to seek, test, treat and retain (STTR) individuals inevidence-based medical care are underway. Evidence isnow required to optimize TasP programmes in order tomaximize their impact on HIV incidence. This is espe-cially true among people who use injection drugs, whocontinue to experience high levels of HIV/AIDS-associ-ated morbidity and mortality and account for more thanone-quarter of incident cases outside sub-Saharan Africa[11]. Since there are concerns that TasP efforts might be* Correspondence: uhri-ew@cfenet.ubc.ca1British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital,Vancouver, British Columbia, Canada2Faculty of Medicine, University of British Columbia, Vancouver, BritishColumbia, Canada© 2013 Milloy et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.Milloy et al. BMC Infectious Diseases 2013, 13:565http://www.biomedcentral.com/1471-2334/13/565compromised by, for example, difficulties detecting acutely-infected individuals [1,12] or improving engagement inthe HIV clinical care cascade [2-4,13], HIV prevention in-terventions will benefit from the identification of expo-sures that are associated with both uncontrolled VL andrisk behaviours for onward HIV transmission (i.e., usedsyringe lending).Among people who inject drugs (PWID), exposure tocorrectional facilities is common and has been con-sistently associated with heightened risk of sharing usedsyringes in custodial [14,15] and non-custodial [16] set-tings. Although many PWID cease injection while incar-cerated, the routine lack of sterile syringes often meanslevels of syringe sharing are typically higher in correc-tional settings than in the community [8,17,18]. As a re-sult, prison-based HIV transmission has been reportedin the United States [9,10,19], Scotland [11,20], Australia[21], Russia [22] and other locations [23,24]. Amongpeople living with HIV, exposure to correctional facilitieshas been associated with sub-optimal HIV treatment in-cluding lower access and adherence to antiretroviraltherapy (ART) [25,26]. However, we are unaware of anystudy that has evaluated the possible effects of both in-carceration on VL non-suppression and used syringelending among PWID living with HIV infection. Thus,in these analyses, we sought to estimate the relationshipsbetween incarceration and VL non-suppression and in-carceration and used syringe lending during periods ofviremia.MethodsTo evaluate these objectives, we used data from theAIDS Care Cohort to evaluate Exposure to Survival Ser-vices (ACCESS), an ongoing prospective observationalcohort of illicit drug users living with HIV/AIDS inVancouver, British Columbia, Canada. Described in de-tail elsewhere [3,27], recruitment for the cohort began inMay, 1996, and focused on the city’s Downtown Eastsideneighbourhood, a post-industrial area with an open drugmarket and high levels of illicit drug use, poverty andHIV infection. We used community-based recruitmentmethods including targeted solicitation of areas wherePWID are known to frequent, such as harm reductionvenues, low-barrier service providers and single-roomoccupancy (SRO) hotels. Individuals are eligible for in-clusion in ACCESS if they are HIV seropositive, areaged ≥ 18 years, have used illicit drugs other than canna-binoids in the previous month. After individuals arescreened for inclusion and offered enrollment in thestudy, they complete an informed consenting process ina private and secure room at the study office. Duringthis process, the participant and a study representativereview a standardized letter which explains the study, itshypotheses and protocols and the possible risks andbenefits of participation. Only individuals who providewritten informed consent are included in the study. At thebaseline interview and every biannual interview thereafter,participants respond to an interviewer-administered ques-tionnaire, are examined by a study nurse and provideblood for serologic analyses. At recruitment, participantsprovide their personal health number (PHN), a uniqueand persistent identifier issued for billing and trackingpurposes to all residents of British Columbia by thegovernment-run universal and no-cost medical system.All study activities were reviewed and approved by theProvidence Health Care/University of British ColumbiaResearch Ethics Board (REB) prior to the commence-ment of the study. The REB reviews the study annually,including any changes to, for example, the recruitmentprocess and all study instruments.Information gathered through the interview and exam-ination process is augmented by data on HIV treatmentand clinical outcomes through a confidential linkage withthe British Columbia Centre for Excellence in HIV/AIDS(BCCfE), as described elsewhere [27]. The BCCfE providesART and related care free of charge to all individuals livingwith HIV/AIDS in British Columbia. Through the linkagea complete retrospective and prospective clinical profile,including data on all ART dispensations, CD4+ cell countsand plasma HIV-1 RNA viral load (PVL) observations, isavailable for each participant.In this study, we included all individuals who had re-ceived at least one day of antiretroviral medication priorto the baseline interview. ART-naïve individuals who initi-ated treatment were included from the next follow-upinterview forward. Individuals without at least one CD4+cell count and PVL observation within ± 180 days of thebaseline interview were excluded from these analyses. Aswell, because our objective was to model the risk of for-ward HIV transmission via contaminated syringes, we ex-cluded an individual’s follow-up period if they did notreport any injection drug use in that period.Using this analytic sample, we tested three hypotheses:First, during any six-month follow-up period, incarcer-ation is associated with higher odds of exhibiting detect-able VL, independent of possible confounding factors. Ifthe first hypothesis is true, we will test the second hy-pothesis: the independent relationship between incarcer-ation and VL non-suppression is mediated by adherenceto ART. Finally, we will test the third hypothesis: incar-ceration is associated with higher odds of used syringelending during periods of VL non-suppression, inde-pendent of possible confounding factors.In the test of the first hypothesis, the primary outcomeof interest was detectable VL in the previous six months,defined as >500 RNA copies/mL plasma. This value wasused as it is the lowest level available throughout thestudy period and is the same as previous analyses of VLMilloy et al. BMC Infectious Diseases 2013, 13:565 Page 2 of 10http://www.biomedcentral.com/1471-2334/13/565from our setting [28,29]. HIV clinical monitoring datawas gathered using each participant’s PHN through theconfidential linkage described above and included all VLand CD4+ measurements conducted through the studyas well as any VL/CD4+ tests conducted outside of thestudy setting, for example, by a participant’s personalphysician. Thus, we were able to include all VL observa-tions conducted in both community and correctionalsettings. In the event that more than one VL observationwas conducted in the prior six months, we included themedian of all observations. The Roche Amplicor Moni-tor assay was used to determine VL from participantblood samples (Roche Molecular Systems, Pleasanton,California).The primary explanatory variable was incarceration ina city jail, provincial prison or federal penitentiary over-night or longer in the six month period prior to theinterview, consistent with previous studies [30,31]. Tobest estimate the effect of incarceration on the likelihoodof VL non-suppression, we considered a range of sec-ondary explanatory variables we hypothesized mightconfound this relationship. These variables were: Age(per year older); gender (female vs. male); Aboriginal an-cestry (yes vs. no); heroin injection (≥ daily vs. < daily);cocaine injection (≥ daily vs. < daily); crack cocaine use(≥ daily vs. < daily); education (≥ high school diplomavs. < high school diploma); homelessness (yes vs. no); in-volvement in sex work (yes vs. no); binge drug use, definedas any period of above-average drug use (yes vs. no); andmethadone maintenance therapy (yes vs. no). All of thebehavioural measures were time-updated and referred tothe six month period prior to the follow-up interview,except for homelessness and MMT, which referred tocurrent status. In addition, we included four clinical vari-ables: HIV MD experience (< 6 patients vs. ≥ 6 patientspreviously treated for HIV); CD4+ cell count (per 100cells); adherence to ART; and the presence of a proteaseinhibitor (PI) in the first ART regimen (yes vs. no). As inprevious research [32,33], our physician experience vari-able was based on how many individuals the participant’sphysician had previously enrolled in the HIV/AIDS treat-ment registry at the time of initiating the participant ontheir first dose of ART. This time-invariant measure wasdichotomized at six patients, as before [32,33]. We havepreviously demonstrated that this measure independentlypredicts VL suppression following ART initiation [33]. Aswith our measure of VL, we included all CD4+ observa-tions conducted by study staff or personal physicians andcalculated a mean of all observations in the previous sixmonths or, if no observations were made, the most recentmeasure. The measure of adherence to antiretroviral ther-apy was the product of the number of days dispensed anti-retroviral therapy in the previous 180 days over thenumber of days eligible in the previous 180 days,dichotomized at above or below 95%. We have used thisvalidated measure of pharmacy refill extensively in previ-ous research [30,34] and have shown it reliably predictsVL suppression [1,35-37] and survival [2-4,32].To determine the final set of secondary explanatoryvariables to include in the multivariate model, we firstestimated bivariate statistics for the relationships be-tween VL non-suppression and each explanatory vari-able of interest over the entire study period usinggeneralized linear mixed-effects analysis. This form ofregression analysis was used to account for the correl-ation between variables gathered over time from thesame individual and, through the use of random inter-cepts, the unobserved variation in the likelihood of non-suppression within each individual [38].Next, using an a priori-defined procedure first de-scribed by Maldonado and Greenland [8,39], we con-structed a multivariate model including the primaryexplanatory variable and all secondary explanatory vari-ables with p-values < 0.4 in bivariate analyses, noting thevalue of the β coefficient associated with incarceration.We then fit a series of multivariate models each withone secondary explanatory variable removed, always not-ing the value of the β coefficient associated with incar-ceration. After fitting all possible models, we removedthe secondary explanatory variable corresponding to thesmallest relative change in the β coefficient for incar-ceration from further consideration and repeated theprocess. This continued until the smallest change fromthe full model exceeded 5%, thus preserving secondaryexplanatory variables with a greater relative impact inthe relationship between incarceration and the likelihoodof non-suppressed VL. This technique has been used inmany studies to estimate the independent effect of avariable on an outcome of interest [9,10,30,40,41]. Toaccount for HIV disease progression, and, in the earlyHAART era, the phenomenon of individuals discontinu-ing therapy at high CD4+ counts to relieve treatmentside-effects, we included CD4+ cell count as an explana-tory covariate in all multivariate models.To test our second hypothesis, that adherence to ARTmediated the relationship between incarceration and VLnon-suppression, we calculated the Sobel test statistic,using β and Standard Errors from regression modelsof incarceration, adherence and VL non-suppression[11,42,43], as in a previous study of age, adherence andVL suppression [12,44].To test our third hypothesis, that incarceration was as-sociated with a greater risk of used syringe lendingamong individuals experiencing viremia, we constructeda second multivariate model using the procedure de-scribed above. The outcome of interest was reportinglending used syringes in the previous six month period,as described in previous analyses [13,45]. The primaryMilloy et al. BMC Infectious Diseases 2013, 13:565 Page 3 of 10http://www.biomedcentral.com/1471-2334/13/565explanatory variable was incarceration in the previoussix months. Secondary explanatory variables consideredwere: Age (per year older); gender (female vs. male);Aboriginal ancestry (yes vs. no); homelessness (yes vs. no);education (≥ high school diploma vs. < high school dip-loma); formal employment (yes vs. no); sex work (yes vs.no); heroin injection (≥ daily vs. < daily); cocaine injection(≥ daily vs. < daily); crack cocaine use (≥ daily vs. < daily);binge drug use (yes vs. no); MMT (yes vs. no); CD4+ cellcount (per 100 cells/mL). We also included a variable forthe year of observation (> 2001 vs. ≤ 2001), as we havepreviously described how local policy changes beginningin 2001, including increasing the supply of syringes, re-moving the requirement individuals return one used syr-inge for every new syringe received and decentralizing thedistribution of syringes, were associated with a reductionin HIV incidence [14,15,46].As above, we calculated bivariate relationships betweensyringe lending and each secondary explanatory variable,retaining explanatory variables with p-values < 0.4 for in-clusion in the full multivariate model. Using an a prioridefined protocol, we fit a series of reduced multivariatemodels to identify secondary explanatory variables withgreater relative influence on the effect of incarceration onused syringe lending. As a last step, we fit the final multi-variate model to best estimate the independent effect ofincarceration on used syringe lending among individualswith non-suppressed VL.ResultsBetween May, 1996 and March, 2012, 1,036 HIV-seropositiveillicit drug users were recruited and completed at leastone interview. Of these, 217 (20.9%) were ART-naïve atrecruitment and throughout the study and were excluded.Of the remaining 819, 783 (95.6%) had complete clinicaldata within 180 days of recruitment and 657 (80.2%) hadat least one period of active injection drug use and wereincluded in these analyses.The 657 participants completed 3929 baseline or follow-up interviews, equal to 1965 person-years of observation.The median number of interviews completed was 4 (inter-quartile range [IQR]: 2, 8) per participant, or 2.4 (0.6, 4.8)per participant. Among the 657 individuals, 455 (69.3%)had at least one period of VL non-suppression. In 3929 in-terviews during the study period, 198 interviews containedreports of used syringe lending from 111 participants. Foreach interview, the median number of days since a CD4+cell count observation was 58 days (IQR: 26, 127) and3798 (96.7%) interviews occurred within 365 days of aCD4+ cell count observation.This analytic sample was comprised of 228 (34.7%)women and 245 (37.3%) individuals reporting Aboriginalancestry. Select socio-demographic, behavioural, struc-tural and clinical characteristics of the participants atthe baseline interview stratified by VL suppression arepresented in Table 1.The first hypothesis evaluated was that incarcerationwas associated with VL non-suppression independent ofrelevant confounders. There were 8,284 VL observationsmade over the entire study period, or a median of 9(IQR: 4, 17) per participant, of which 3,314 (40.0%) indi-cated 500 HIV-1 RNA copies or greater per mL plasma.Non-suppression of VL was observed in 1972 (50.2%) of3929 interviews. The crude and adjusted longitudinal es-timates of the odds of VL non-suppression are presentedin Table 2. In addition, in a sub-analysis, we observed asignificant relationship between VL non-suppression andreporting used syringe lending (OR = 1.99, 95% CI: 1.30,3.05, p = 0.002).Over the entire study period, incarceration was common,with 594 (15.1%) of all interviews including a report of atleast one incarceration event in the previous six months.Among all participants, 235 (35.8%) were incarcerated atleast once; among individuals ever incarcerated, the mediannumber of periods including incarceration was 2 (IQR = 1,3). Individuals incarcerated during the previous six monthshad at least double the odds of VL non-suppression com-pared to non-incarcerated individuals (OR = 2.00, 95%CI: 1.47, 2.72, p < 0.001). In a multivariate model adjustedfor age, CD4+ cell count, engagement in MMT, heroin in-jection and homelessness, incarceration was independ-ently associated with higher odds of VL non-suppression(Adjusted Odds Ratio = 1.54, 95% CI: 1.10, 2.16, p = 0.011).In a sub-analysis, we repeated the protocol adding yearof observation to the model-building protocol (resultsnot shown). Our results were not significantly different.The second hypothesis was that ART adherence medi-ated the relationship between incarceration and VL non-suppression. A statistical test of mediation was significant(Sobel test = 4.09, p < 0.001).The third hypothesis was that incarceration was asso-ciated with used syringe lending during periods of VLnon-suppression, independent of potential confounders.Of the 198 interviews with a report of used syringe lend-ing, 132 (66.7%) occurred during periods of VL non-suppression. Crude and adjusted longitudinal estimatesof factors associated with used syringe lending among455 active PWID with non-suppressed VL are presentedin Table 3. Compared to non-incarcerated individuals,individuals reporting incarceration had almost doublethe odds of used syringe lending (OR = 1.76, 95% CI: 1.01,3.05, p = 0.046). In the multivariate model, incarcerationwas independently associated with lending used syringes(AOR = 1.81, 95% CI: 1.03, 3.18, p = 0.038).DiscussionIn these analyses of data from a long-running community-recruited cohort of active PWID, we observed a high levelMilloy et al. BMC Infectious Diseases 2013, 13:565 Page 4 of 10http://www.biomedcentral.com/1471-2334/13/565Table 1 Baseline characteristics of 657 ART-exposed active PWID in Vancouver, Canada stratified by plasma HIV-1 RNAviral load (VL) non-suppression, 1996 – 2012Characteristic VL suppressed VL non-suppressed Odds ratio 95% CI2 p-value153 (23.3) 504 (76.7)n (%) n (%)Incarceration3No 227 (87.3) 312 (78.6) 1.00Yes 33 (12.7) 85 (21.4) 1.87 1.21, 2.90 0.005AgeMedian (IQR) 45.3 (39.5 – 50.7) 37.9 (33.1 – 43.9) 0.98 0.98, 0.98 < 0.001GenderMale 191 (73.5) 238 (60.0) 1.00Female 69 (26.5) 159 (40.0) 1.85 1.32, 2.60 < 0.001Aboriginal ancestryNo 172 (66.2) 240 (60.5) 1.00Yes 88 (33.8) 157 (39.5) 1.28 0.92, 1.77 0.161Heroin injection< Daily 230 (88.5) 293 (73.8) 1.00≥ Daily 30 (11.5) 104 (26.2) 2.72 1.75, 4.23 < 0.001Cocaine injection< Daily 227 (87.3) 289 (72.8) 1.00≥ Daily 33 (12.7) 108 (27.2) 2.57 1.68, 3.94 < 0.001Crack cocaine use< Daily 164 (63.1) 291 (73.3) 1.00≥ Daily 96 (36.9) 106 (26.7) 0.62 0.44, 0.87 0.007Education< High school diploma 136 (52.3) 252 (63.5) 1.00≥ High school diploma 124 (47.7) 145 (36.5) 0.63 0.46, 0.87 0.005HomelessNo 243 (93.5) 352 (88.7) 1.00Yes 17 (6.5) 45 (11.3) 1.83 1.02, 3.27 0.041Sex work3No 235 (90.4) 328 (82.6) 1.00Yes 25 (9.6) 69 (17.4) 1.98 1.21, 3.22 0.006HIV MD experience≥ 6 patients 223 (85.8) 320 (80.6) 1.00< 6 patients 37 (14.2) 77 (19.4) 1.45 0.95, 2.22 0.093PI in first ART regimenNo 160 (61.5) 238 (59.9) 1.00Yes 100 (38.5) 150 (40.1) 1.07 0.78, 1.47 0.744CD4+ cells (per 100/mm3)Median (IQR) 3.6 (2.4 – 4.9) 2.6 (1.5 – 4.0) 0.95 0.94, 0.97 < 0.001ART adherence≤ 95% 102 (39.2) 377 (95.0) 1.00> 95% 158 (60.8) 20 (5.0) 0.03 0.02, 0.06 < 0.001295% Confidence Interval (95% CI).3Refers to 180 day period prior to baseline interview.Milloy et al. BMC Infectious Diseases 2013, 13:565 Page 5 of 10http://www.biomedcentral.com/1471-2334/13/565of VL non-suppression. Uncontrolled VL was observed inmore than half of all baseline and follow-up interview pe-riods; more than two-thirds of all participants experiencedat least one period of uncontrolled VL. In a multivariatemodel adjusted for a range of clinical, behavioural andstructural correlates of non-suppression, incarcerationwas independently associated with greater odds of VLnon-suppression. In a second multivariate model amongPWID at risk of onward transmission, incarceration wasindependently associated with a greater likelihood of usedsyringe lending.As with all observational studies, we cannot excludethe possibility that the observed association betweenincarceration and VL non-suppression is influenced by re-sidual confounding. However, a number of lines of evi-dence support a causal relationship between exposure tocorrectional facilities and elevated viral load. Althoughcorrectional systems select for populations marked byTable 2 Crude and adjusted longitudinal estimates of the odds of plasma HIV-1 RNA viral load non-suppression among657 ART-exposed active PWID, Vancouver, 1996 – 2012Characteristic OR1 95% CI2 p-value AOR3 95% CI p-valueIncarceration4Yes vs. no 2.00 1.47 – 2.72 < 0.001 1.54 1.10, 2.16 0.011AgePer year 0.90 0.87 – 0.92 < 0.001 0.91 0.88, 0.94 < 0.001GenderFemale vs. male 1.69 1.07 – 2.67 0.024Aboriginal ancestryYes vs. no 1.35 0.86 – 2.11 0.189Homeless5Yes vs. no 2.38 1.59 – 3.58 < 0.001 1.83 1.19, 2.82 0.006Education≥HS vs < HS 0.89 0.66 – 1.22 0.476Employment4Yes vs. no 0.48 0.25 – 0.92 0.028Heroin injection4≥ Daily vs. < daily 2.76 2.07 – 3.69 < 0.001 2.09 1.53, 2.87 <0.001Cocaine injection4≥ Daily vs. < daily 1.52 1.18 – 1.97 0.001Crack cocaine use4≥ Daily vs. < daily 1.37 1.06 – 1.76 0.015Binge drug use4Yes vs. no 1.09 0.88 – 1.36 0.426MMT5Yes vs. no 0.46 0.35 – 0.59 < 0.001 0.52 0.39, 0.70 < 0.001Sex work4Yes vs. no 2.21 1.47 – 3.33 < 0.001HIV MD experience< 6 patients vs. ≥ 6 1.93 1.08 – 3.46 0.026PI in first ART regimenYes vs. no 1.06 0.68 – 1.67 0.794CD4+ cell count4Per 100 cells/mL 0.48 0.44 – 0.53 < 0.001 0.51 0.47, 0.56 < 0.001ART adherence4≥ 95% vs < 95% 0.03 0.02 – 0.04 < 0.0011Odds Ratio; 295% Confidence Interval; 3Adjusted Odds Ratio; 4Refers to the six month period prior to follow-up; 5Refers to current status.Milloy et al. BMC Infectious Diseases 2013, 13:565 Page 6 of 10http://www.biomedcentral.com/1471-2334/13/565high levels of various risks for sub-optimal HIV treatmentoutcomes, such as more severe addiction, our findingspersisted even after they were adjusted for a range of sig-nificant factors, including homelessness, high-intensityillicit drug use, age and immunologic status. Consistentwith the hypothesis that incarceration may contributeto antiretroviral interruption, prior studies of virally-suppressed PWID on ART in Vancouver, BC [17,18,31],and Baltimore, Maryland [19,26] identified incarcerationas a strong independent risk factor for virologic rebound.Second, our finding that incarceration-related VL non-suppression is driven by poorer ART adherence is consist-ent with a range of previous analyses. For example, werecently demonstrated that the number of incarcerationepisodes experienced longitudinally was strongly associ-ated with non-adherence to prescribed treatment in adose-dependent fashion [20,30], in line with previous workisolating transfer between correctional/non-correctionalenvironments [21,25] and prison-related HIV stigma asbarriers to optimal ART adherence [22,47].Our findings should be considered in light of increas-ing efforts to implement HIV treatment as prevention.Globally, HIV incidence among PWID remains high des-pite a range of effective evidence-based HIV preventioninterventions, including sterile syringe distribution, opi-oid substitution therapies and supervised injection facil-ities [25,26,48]. Although these interventions are, by andlarge, simple and cost-effective, coverage remains low inTable 3 Crude and adjusted longitudinal estimates of the odds of used syringe lending among 455 ART-exposed activePWID with unsuppressed plasma HIV-1 RNA viral loads, Vancouver, Canada, 1996 – 2012Characteristic OR1 95% CI2 p-value AOR3 95% CI p-valueIncarceration4Yes vs. no 1.76 1.01 – 3.05 0.046 1.81 1.03, 3.18 0.038Age5Per year 1.03 0.94 – 1.13 0.515GenderFemale vs. male 1.09 0.23 – 5.08 0.916Aboriginal ancestryYes vs. no 0.30 0.09 – 0.96 0.043Homeless5Yes vs. no 1.18 0.40 – 3.47 0.759Education5≥ HS vs. < HS 0.82 0.36 – 1.86 0.635Employment4Yes vs. no 3.55 0.53 – 23.99 0.193Heroin injection4≥ Daily vs. < daily 0.77 0.35 – 1.70 0.520Cocaine injection4≥ Daily vs. < daily 1.27 0.64 – 2.51 0.500Crack cocaine use4≥ Daily vs. < daily 0.86 0.40 – 1.84 0.691Binge drug use4Yes vs. no 1.28 0.72 – 2.29 0.397MMT5Yes vs. no 1.27 0.58 – 2.79 0.553Sex work4Yes vs. no 1.72 0.67 – 4.44 0.259Year of observation> 2001 vs ≤ 2001 0.11 0.03 – 0.36 < 0.001 0.15 0.08, 0.29 < 0.001CD4+ cell countPer 100 cells/mL 1.17 0.95 – 1.44 0.1421Odds Ratio; 295% Confidence Interval; 3Adjusted Odds Ratio; 4Refers to the six month period prior to follow-up; 5Refers to current status.Milloy et al. BMC Infectious Diseases 2013, 13:565 Page 7 of 10http://www.biomedcentral.com/1471-2334/13/565many jurisdictions as criminal justice-based interven-tions remain the dominant response to injection druguse [3,23,27]. There is a clear danger that this dynamicwill be repeated and the effect of TasP-based efforts tocurb elevated HIV incidence among PWID will be com-promised by incarceration-related barriers to HIV treat-ment. To date, there has been little discussion of theeffect of the criminalization of PWID on TasP imple-mentation as concerns have focused on behavioural fac-tors associated with adherence [27,49]. Our evidence ofthe role played by incarceration on VL and HIV risk be-haviours is an example of why structural dynamics mustbe considered in all combination HIV prevention inter-ventions, including TasP [30,31,50,51].As the HIV/AIDS pandemic enters its fourth decade,correctional facilities remain important foci of HIV inci-dence and prevalence, especially in Canada, the UnitedStates, areas of the former Soviet Union and south andsoutheast Asia [24,32,52,53]. Although data is incom-plete, the prevalence of HIV infection is typically severaltimes higher in detained populations compared to thegeneral population and surpasses 10% in several jurisdic-tions [32,52]. Although some studies have demonstratedimpressive clinical gains for people who are incarceratedand living with HIV/AIDS [30,34,54-56], and studies areunderway of STTR efforts within a number of correc-tional systems in the United States [57], several prison-related barriers to optimal HIV treatment are commonin many jurisdictions, including sub-standard healthcarefacilities, poor continuity of care between correctionaland non-correctional health systems, lack of care forHIV-related co-morbidities such as addiction and an em-phasis on public security over public health [24,58,59]. InCanada, although the most recently released infectiousdisease surveillance data from 2007 reported that 1.6percent of male and 4.7 percent of female individualsdetained in the federal penitentiary system in 2007 wereliving with HIV/AIDS [60], we are unaware of any formalefforts to prevent prison-based HIV transmission throughSTTR initiatives. Further, officials in many settings haveconsistently refused to implement any prison-based needleexchange programmes, despite clear evidence of ongoingillicit drug use and syringe sharing within prisons and re-peated calls by people who use injection drugs, physicians,legal experts and advocates [61,62]. Our current findingssuggest that investments in HIV prevention and treatmentefforts may be undercut by the lack of HIV preventionand treatment in prisons, especially among people whouse injection drugs.This research has some limitations. First, no registriesof HIV-seropositive PWID exist and thus our analyticsample cannot be seen as representative of all HIV-positive PWID in this setting or others. Second, as men-tioned above, we cannot exclude the possible existenceof unmeasured confounding, however we sought to mini-mize its influence by multivariate modeling and the use ofdata a large and long-running community-recruited pro-spective cohort of illicit drug users. Third, our measure ofincarceration was based on self-report as administrativedata was unavailable. Fourth, we were unable to determinewhether VL measurements occurred prior to, during orfollowing an incarceration event. Our primary outcome ofinterest was ascertained through data from the local com-prehensive provider of HIV clinical monitoring in a settingwith no financial barriers to healthcare and we are un-aware of any reason individuals might differentially reportincarceration history based on their viral load status.ConclusionsTo conclude, we used data from an ongoing prospectivecohort of HIV-seropositive PWID with comprehensiveclinical monitoring data and found incarceration was anindependently associated with both non-suppression ofPVL and used syringe sharing. To our knowledge, this isthe first study to exploit recent advances in knowledgeof VL and risk behaviours to model the risks of onwardHIV transmission among people living with HIV infection.Our findings re-emphasize the importance of consideringthe structural determinants of HIV transmission, espe-cially in the new era of combination HIV prevention inter-ventions involving traditional HIV prevention strategieswith the use of antiretroviral therapy. They also highlightthe urgent need to identify and remove incarceration-related barriers to effective HIV treatment to addresspersistently high levels of HIV incidence and HIV/AIDS-related morbidity and mortality among peoplewho use injection drugs. Finally, our results suggest thatalternatives to incarceration of non-violent PWID andevidence-based combination HIV prevention interven-tions for PWID within correctional facilities are urgentlyneeded.Competing interestsThe authors state that they have no competing financial or non-financialinterests. Dr. Montaner has also received financial support from theInternational AIDS Society, United Nations AIDS Program, World HealthOrganization, National Institutes of Health Research-Office of AIDS Research,National Institute of Allergy & Infectious Diseases, The United StatesPresident’s Emergency Plan for AIDS Relief (PEPfAR), UNICEF, the Universityof British Columbia, Simon Fraser University, Providence Health Care andVancouver Coastal Health Authority. He has received grants from Abbott,Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merckand ViiV Healthcare.Authors’ contributionsM-JM, EW and TK conceived the analysis; M-JM conducted the statistical ana-lysis and drafted and revised the manuscript; HS, KS, SG, JM, M-JM, EW andTK designed the study, coordinated the gathering of clinical, laboratory andinterview data, reviewed and commented on the analysis and the manu-script. All authors read and approved the final version of the manuscript.Milloy et al. BMC Infectious Diseases 2013, 13:565 Page 8 of 10http://www.biomedcentral.com/1471-2334/13/565AcknowledgementsThe authors thank the study participants for their contributions to theresearch, as well as current and past researchers and staff. We wouldspecifically like to thank Deborah Graham, Tricia Collingham, Carmen Rock,Brandon Marshall, Caitlin Johnston, Steve Kain and Benita Yip for their researchand administrative assistance. The was work was supported by the US NationalInstitutes of Health [grant number R01-DA021525]; and the Canadian Institutesof Health Research [grant number MOP-79297, RAA-79918]. Dr. Milloy issupported by the Michael Smith Foundation for Health Research and theCanadian Institutes of Health Research. This work was supported in part by aTier 1 Canada Research Chair in Inner-City Medicine awarded to Dr. Wood.Dr. Montaner is supported by the Ministry of Health Services and the Ministry ofHealthy Living and Sport, from the Province of British Columbia; through aKnowledge Translation Award from CIHR; and through an Avant-Garde Award[1DP1DA026182-01] from the National Institute of Drug Abuse at the USNational Institutes of Health.Received: 30 May 2013 Accepted: 18 November 2013Published: 1 December 2013References1. Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, Kornegay J,Jackson B, Moye J, Hanson C, Zorrilla C, Lew JF: Maternal levels of plasmahuman immunodeficiency virus type 1 RNA and the risk of perinataltransmission. Women and infants transmission study group. N Engl J Med1999, 341:394–402.2. Das M, Chu PL, Santos G-M, Scheer S, Vittinghoff E, McFarland W, Colfax GN:Decreases in community viral load are accompanied by reductions innew HIV Infections in San Francisco. PLoS One 2010, 5:e11068.3. Wood E, Kerr T, Marshall BDL, Li K, Zhang R, Hogg RS, Harrigan PR, MontanerJSG: Longitudinal community plasma HIV-1 RNA concentrations andincidence of HIV-1 among injecting drug users: prospective cohortstudy. BMJ 2009, 338:b1649–b1649.4. Montaner JSG, Lima VD, Barrios R, Yip B, Wood E, Kerr T, Shannon K,Harrigan PR, Hogg RS, Daly P, Kendall P: Association of highly activeantiretroviral therapy coverage, population viral load, and yearly newHIV diagnoses in British Columbia, Canada: a population-based study.Lancet 2010, 376:532–539.5. Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG: Universal voluntaryHIV testing with immediate antiretroviral therapy as a strategy forelimination of HIV transmission: a mathematical model. Lancet 2009,373:48–57.6. Charlebois ED, Das M, Porco TC, Havlir DV: The effect of expandedantiretroviral treatment strategies on the HIV epidemic among men whohave sex with men in San Francisco. Clin Infect Dis 2011, 52:1046–1049.7. Sorensen SW, Sansom SL, Brooks JT, Marks G, Begier EM, Buchacz K,Dinenno EA, Mermin JH, Kilmarx PH: A mathematical model ofcomprehensive test-and-treat services and HIV incidence among menwho have sex with men in the United States. PLoS One 2012, 7:e29098.8. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC,Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JHS, GodboleSV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF,Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de BruynG, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V,Burns D, et al: Prevention of HIV-1 infection with early antiretroviraltherapy. N Engl J Med 2011, 365:493–505.9. Coates TJ, Richter L, Caceres C: Behavioural strategies to reduce HIVtransmission: how to make them work better. Lancet 2008, 372:669–684.10. Hull MW, Wu Z, Montaner JSG: Optimizing the engagement of carecascade: a critical step to maximize the impact of HIV treatment asprevention. Curr Opin HIV AIDS 2012, 7:579–586.11. Mathers BM, Degenhardt L, Phillips B, Wiessing L, Hickman M, Strathdee SA,Wodak A, Panda S, Tyndall M, Toufik A, Mattick RP, 2007 Reference Group tothe UN on HIV and Injecting Drug Use: Global epidemiology of injectingdrug use and HIV among people who inject drugs: a systematic review.Lancet 2008, 372:1733–1745.12. Cohen MS, Muessig KE, Smith MK, Powers KA, Kashuba ADM: Antiviralagents and HIV prevention: controversies, conflicts, and consensus.AIDS 2012, 26:1585–1598.13. Hull MW, Montaner J: Antiretroviral therapy: a key component of acomprehensive HIV prevention strategy. Curr HIV/AIDS Rep 2011, 8:85–93.14. Pollini RA, Alvelais J, Gallardo M, Vera A, Lozada R, Magis-Rodriquez C,Strathdee SA: The harm inside: injection during incarceration amongmale injection drug users in Tijuana, Mexico. Drug Alcohol Depend 2009,103:52–58.15. Malliori M, Sypsa V, Psichogiou M, Touloumi G, Skoutelis A, Tassopoulos N,Hatzakis A, Stefanis C: A survey of bloodborne viruses and associated riskbehaviours in Greek prisons. Addiction 1998, 93:243–251.16. Milloy M-JS, Buxton J, Wood E, Li K, Montaner JSG, Kerr T: Elevated HIV riskbehaviour among recently incarcerated injection drug users in a Canadiansetting: a longitudinal analysis. BMC Public Health 2009, 9:156.17. Darke S, Kaye S, Finlay-Jones R: Drug use and injection risk-taking amongprison methadone maintenance patients. Addiction 1998, 93:1169–1175.18. López-Zetina J, Kerndt P, Ford W, Woerhle T, Weber M: Prevalence of HIV andhepatitis B and self-reported injection risk behavior during detentionamong street-recruited injection drug users in Los Angeles County,1994–1996. Addiction 2001, 96:589–595.19. Centers for Disease Control and Prevention (CDC): HIV transmission amongmale inmates in a state prison system–Georgia, 1992–2005. MMWR MorbMortal Wkly Rep 2006, 55:421–426.20. Taylor A, Goldberg D, Emslie J, Wrench J, Gruer L, Cameron S, Black J, Davis B,McGregor J, Follett E: Outbreak of HIV infection in a Scottish prison. BMJ1995, 310:289–292.21. Dolan KA, Wodak A: HIV transmission in a prison system in an AustralianState. Med J Aust 1999, 171:14–17.22. Bobrik A, Danishevski K, Eroshina K, McKee M: Prison health in Russia: thelarger picture. J Public Health Pol 2005, 26:30–59.23. The Global Commission On Drug Policy: The War on Drugs and HIV/AIDS.Global Commission on Drug Policy; 2012:1–24.24. Jürgens R, Nowak M, Day M: HIV and incarceration: prisons and detention.J Int AIDS Soc 2011, 14:26.25. Baillargeon J, Giordano TP, Rich JD, Wu ZH, Wells K, Pollock BH, Paar DP:Accessing antiretroviral therapy following release from prison. JAMA2009, 301:848–857.26. Westergaard RP, Kirk GD, Richesson DR, Galai N, Mehta SH: Incarcerationpredicts virologic failure for hiv-infected injection drug users receivingantiretroviral therapy. Clin Infect Dis 2011, 53:725–731.27. Strathdee S, Palepu A, Cornelisse PG, Yip B, O'shaughnessy MV, Montaner JS,Schechter MT, Hogg RS: Barriers to use of free antiretroviral therapy ininjection drug users. JAMA 1998, 280:547–549.28. Kerr T, Marshall BDL, Milloy M-J, Zhang R, Guillemi S, Montaner JSG, Wood E:Patterns of heroin and cocaine injection and plasma HIV-1 RNA suppressionamong a long-term cohort of injection drug users. Drug Alcohol Depend2012, 124:1–5.29. Krusi A, Milloy M-J, Kerr T, Zhang R, Guillemi S, Hogg R, Montaner J, Wood E:Ongoing drug use and outcomes from highly active antiretroviral therapyamong injection drug users in a Canadian setting. Antivir Ther (Lond) 2010,15:789–796.30. Milloy M-J, Kerr T, Buxton J, Rhodes T, Guillemi S, Hogg R, Montaner J, Wood E:Dose–response effect of incarceration events on nonadherence to HIVantiretroviral therapy among injection drug users. J Infect Dis 2011,203:1215–1221.31. Milloy M-J, Kerr T, Buxton J, Rhodes T, Krusi A, Guillemi S, Hogg R, Montaner J,Wood E: Social and environmental predictors of plasma HIV RNA reboundamong injection drug users treated with antiretroviral therapy. J AcquirImmune Defic Syndr 2012, 59:393–399.32. Wood E, Hogg RS, Lima VD, Kerr T, Yip B, Marshall BDL, Montaner JSG:Highly active antiretroviral therapy and survival in HIV-infected injectiondrug users. JAMA 2008, 300:550–554.33. Sangsari S, Milloy M-J, Ibrahim A, Kerr T, Zhang R, Montaner J, Wood E:Physician experience and rates of plasma HIV-1 RNA suppressionamong illicit drug users: an observational study. BMC Infect Dis 2012,12:22.34. Milloy M-J, Kerr T, Bangsberg DR, Buxton J, Parashar S, Guillemi S, MontanerJ, Wood E: Homelessness as a structural barrier to effective antiretroviraltherapy among HIV-seropositive illicit drug users in a Canadian setting.AIDS Patient Care STDS 2012, 26:60–67.35. Low-Beer S, Yip B, O'Shaughnessy MV, Hogg RS, Montaner JS: Adherence totriple therapy and viral load response. JAIDS J Acquir Immune Defic Syndr2000, 23:360–361.36. Palepu A, Yip B, Miller C, Strathdee SA, O'Shaughnessy MV, Montaner JS,Hogg RS: Factors associated with the response to antiretroviral therapyMilloy et al. BMC Infectious Diseases 2013, 13:565 Page 9 of 10http://www.biomedcentral.com/1471-2334/13/565among HIV-infected patients with and without a history of injectiondrug use. AIDS 2001, 15:423–424.37. Wood E, Montaner JSG, Yip B, Tyndall MW, Schechter MT, O'shaughnessyMV, Hogg RS: Adherence and plasma HIV RNA responses to highly activeantiretroviral therapy among HIV-1 infected injection drug users. CMAJ2003, 169:656–661.38. Finucane MM, Samet JH, Horton NJ: Translational methods in biostatistics:linear mixed effect regression models of alcohol consumption and HIVdisease progression over time. Epidemiol Perspect Innov 2007, 4:8.39. Maldonado G, Greenland S: Simulation study of confounder-selectionstrategies. Am J Epidemiol 1993, 138:923–936.40. Lima V, Fernandes K, Rachlis B, Druyts E, Montaner J, Hogg R: Migrationadversely affects antiretroviral adherence in a population-based cohortof HIV/AIDS patients. Soc Sci Med 2009, 68:1044–1049.41. Marshall BDL, Kerr T, Shoveller JA, Patterson TL, Buxton JA, Wood E:Homelessness and unstable housing associated with an increased risk ofHIV and STI transmission among street-involved youth. Health Place 2009,15:753–760.42. Sobel ME: Asymptotic intervals for indirect effects in structural equationsmodels. In Sociological methodology. Edited by Leinhart S. San Francisco,California: Jossey-Bass; 1982:290–312.43. MacKinnon DP, Lockwood CM, Hoffman JM, West SG, Sheets V: A comparisonof methods to test mediation and other intervening variable effects.Psychol Methods 2002, 7:83–104.44. Hadland SE, Milloy M-J, Kerr T, Zhang R, Guillemi S, Hogg RS, Montaner JS,Wood E: Young age predicts poor antiretroviral adherence and viral loadsuppression among injection drug users. AIDS Patient Care STDS 2012,26:274–280.45. Kuyper L, Milloy M-J, Marshall BDL, Zhang R, Kerr T, Montaner JSG, Wood E:Does initiation of HIV antiretroviral therapy influence patterns of syringelending among injection drug users? Addict Behav 2011, 36:560–563.46. Kerr T, Small W, Buchner C, Zhang R, Li K, Montaner J, Wood E: Syringesharing and HIV incidence among injection drug users and increasedaccess to sterile syringes. Am J Public Health 2010, 100:1449–1453.47. Small W, Wood E, Betteridge G, Montaner J, Kerr T: The impact ofincarceration upon adherence to HIV treatment among HIV-positiveinjection drug users: a qualitative study. AIDS Care 2009, 21:708–714.48. Mathers BM, Degenhardt L, Ali H, Wiessing L, Hickman M, Mattick RP, MyersB, Ambekar A, Strathdee SA: HIV prevention, treatment, and care servicesfor people who inject drugs: a systematic review of global, regional, andnational coverage. Lancet 2010, 375:1014–1028.49. Milloy MJ, Montaner J, Wood E: Barriers to HIV treatment among peoplewho use injection drugs: implications for ‘treatment as prevention’. CurrOpin HIV AIDS 2012, 7:332–338.50. Strathdee SA, Shoptaw S, Dyer TP, Quan VM, Aramrattana A, SubstanceUse Scientific Committee of the HIV Prevention Trials Network: Towardscombination HIV prevention for injection drug users: addressingaddictophobia, apathy and inattention. Curr Opin HIV AIDS 2012,7:320–325.51. Padian NS, McCoy SI, Manian S, Wilson D, Schwartländer B, Bertozzi SM:Evaluation of large-scale combination HIV prevention programs: essentialissues. J Acquir Immune Defic Syndr 2011, 58:e23–e28.52. Dolan K, Kite B, Black E, Aceijas C, Stimson GV: Reference group on HIV/AIDSprevention and care among injecting drug users in developing andtransitional countries: HIV in prison in low-income and middle-incomecountries. Lancet Infect Dis 2007, 7:32–41.53. Spaulding AC, Seals RM, Page MJ, Brzozowski AK, Rhodes W, Hammett TM:HIV/AIDS among inmates of and releasees from US correctional facilities,2006: declining share of epidemic but persistent public healthopportunity. PLoS One 2009, 4:A16–A21.54. Springer S, Friedland G, Doros G, Pesanti E, Altice F: Antiretroviral treatmentregimen outcomes among hiv-infected prisoners. HIV Clin Trials 2007,8:205–212.55. Springer SA, Pesanti E, Hodges J, Macura T, Doros G, Altice FL: Effectivenessof antiretroviral therapy among HIV-infected prisoners: reincarcerationand the lack of sustained benefit after release to the community.Clin Infect Dis 2004, 38:1754–1760.56. Davies N, Karstaedt AS: Antiretroviral outcomes in South Africanprisoners: a retrospective cohort analysis. PLoS One 2012, 7(3):e33309.57. Older S: Unprecedented effort to seek, test, and treat inmates with HIV: NIHresearch to improve public health with focus on prison on jail systems acrossthe United States. NIH News; 2010:1–3.58. Flanigan TP, Beckwith CG: The intertwined epidemics of hiv infection,incarceration, and substance abuse: a call to action. J Infect Dis 2011,203:1201–1203.59. Fazel S, Baillargeon J: The health of prisoners. Lancet 2011, 377:956–965.60. Public Health Branch, Health Services Sector of Correctional Service Canada(CSC): Infectious Disease Surveillance in Canadian Federal Penitentiaries (2007–2008).Ottawa, Ontario, Canada: Correctional Service Canada; 2009:1–17.61. Small W, Kain S, Laliberte N, Schechter MT, O'shaughnessy MV, Spittal PM:Incarceration, addiction and harm reduction: inmates experienceinjecting drugs in prison. Subst Use Misuse 2005, 40:831–843.62. Milloy M-J, Wood E, Small W, Tyndall M, Lai C, Montaner J, Kerr T: Incarcerationexperiences in a cohort of active injection drug users. Drug Alcohol Rev2008, 27:693–699.doi:10.1186/1471-2334-13-565Cite this article as: Milloy et al.: Incarceration is associated with usedsyringe lending among active injection drug users with detectableplasma HIV-1 RNA: a longitudinal analysis. BMC Infectious Diseases2013 13:565.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitMilloy et al. BMC Infectious Diseases 2013, 13:565 Page 10 of 10http://www.biomedcentral.com/1471-2334/13/565

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.52383.1-0215976/manifest

Comment

Related Items