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Suboptimal plasma HIV-1 RNA suppression and adherence among sex workers who use illicit drugs in a Canadian… Lianping, Ti; Milloy, M-J; Shannon, Kate; Simo, Annick; Hogg, Robert S.; Guillemi, Sylvia; Montaner, Julio; Kerr, Thomas; Wood, Evan Feb 12, 2014

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SUBOPTIMAL PLASMA HIV-1 RNA SUPPRESSION ANDADHERENCE AMONG SEX WORKERS WHO USE ILLICIT DRUGSIN A CANADIAN SETTING: AN OBSERVATIONAL COHORTSTUDYLianping Ti1,2, M-J Milloy1,3, Kate Shannon1,4, Annick Simo1, Robert S Hogg1,5, SylviaGuillemi1, Julio Montaner1,4, Thomas Kerr1,4, and Evan Wood1,41British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital, Vancouver, BritishColumbia, Canada2School of Population and Public Health, University of British Columbia, Vancouver, BritishColumbia, Canada3Department of Family Practice, University of British Columbia, Vancouver, British Columbia,Canada4Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada5Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, CanadaAbstractObjective—Studies have demonstrated the central function of plasma HIV-1 RNA viral load(pVL) levels on determining the risk of HIV disease progression and transmission. However, thereis limited empirical research on virologic outcomes among sex workers who use illicit drugs (SW-DU).Methods—Data were derived from the AIDS Care Cohort to evaluate Exposure to SurvivalServices, a cohort of HIV-positive illicit drug users. Using generalised estimating equations, westudied the longitudinal relationship between sex work and pVL suppression. We also testedwhether adherence to antiretroviral therapy (ART) mediated the relationship between sex workand pVL suppression.Results—Between May 1996 and May 2012, 587 ART-exposed participants (2224 person-yearsof observation) were included in the study, among whom 127 (21.6%) reported sex work. In atime-updated multivariate model adjusted for various demographic, socioeconomic and clinicalconfounders (eg, gender, incarceration, CD4 cell count), SW-DU had an independently reducedCorresponding author: Evan Wood British Columbia Centre for Excellence in HIV/AIDS 608-1081 Burrard Street Vancouver, BCV6Z 1Y6 Canada Tel: (604) 806-9116 uhri-ew@cfenet.ubc.ca.Contributors The specific contributions of each author are as follows: LT, M-JM and EW were responsible for the study design; ASconducted the statistical analyses; LT prepared the first draft of the manuscript; M-JM, KS, AS, RSH, SG, JM, TK and EW providedcritical comments on the first draft of the manuscript and approved the final version to be submitted.Ethics Approval University of British Columbia/Providence Healthcare Research Ethics Board.Competing Interests For the remaining authors, no conflicts of interest were declared.NIH Public AccessAuthor ManuscriptSex Transm Infect. Author manuscript; available in PMC 2015 August 01.Published in final edited form as:Sex Transm Infect. 2014 August ; 90(5): 418–422. doi:10.1136/sextrans-2013-051408.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptodds of pVL suppression compared to non-SW-DU (adjusted OR (AOR)=0.66; 95% CI 0.45 to0.96). However, adding ART adherence to the multivariate model eliminated this association(p>0.05), suggesting adherence mediated the relationship between sex work and pVL suppression.Conclusions—Evidence-based interventions to improve adherence to ART among SW-DU areurgently needed to help produce the maximum HIV treatment and prevention benefit of ARTamong this highly vulnerable population.INTRODUCTIONAdvancements in the clinical management of HIV infection through the use of antiretroviraltherapy (ART) have resulted in dramatic declines in HIV-related morbidity and mortalityamong people living with HIV.1 Optimal adherence to ART is strongly associated withreducing plasma HIV-1 RNA viral load (pVL), slowing HIV disease progression andprolonging survival.2 Additionally, recent studies have demonstrated the central role playedby pVL on HIV transmission dynamics.3 In light of these findings, the HIV treatment asprevention approach (TasP) has been endorsed by a number of major international publichealth bodies, including the Joint United Nations Programme on HIV/AIDS and the WorldHealth Organization (WHO), with various models to seek, test, treat and retain individualsin treatment being implemented worldwide.4However, among people who use illicit drugs (DU), the successful clinical management ofHIV infection is complicated by individual, social and structural factors that often impedeoptimal outcomes from ART.5 For instance, although evidence has linked ongoing illicitdrug use to greater risk of suboptimal ART adherence,6 recent studies have also highlightedthe array of social, structural and environmental barriers that DU often contend with as afunction of drug addiction. These include high rates of homelessness7 and incarceration,8often resulting in suboptimal adherence and clinical outcomes.Sex workers who use illicit drugs (SW-DU) face particularly high risks of HIV infection,9with increasing research over the last decade in North America and the UK suggesting thatSWDU face among the highest rates of new HIV infections among DU.10 Furthermore, arecent meta-analysis of 50 low-income and middle-income countries revealed an overallprevalence of HIV of 11.8% and a pooled OR for HIV of 13.5 among female sex workers(SW) compared to the general population of women of reproductive age.11 However, thereis a near-complete dearth of information regarding plasma HIV-1 RNA outcomes amongSW in high-income settings, particularly SW-DU, with free HIV/AIDS treatment and care.To address this, we sought to investigate the effect of sex work on virologic outcomesamong DU in a setting of universal HIV/AIDS care.METHODSStudy designData were collected from the AIDS Care Cohort to Evaluate Access to Survival Services(ACCESS), a prospective cohort study of HIV-positive DU in Vancouver, Canada. Thespecific methods employed have been described in detail elsewhere.12 In brief, beginning in1996, participants were recruited through self-referral and street-based outreach fromTi et al. Page 2Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptVancouver’s Downtown Eastside neighbourhood, a postindustrial area with a large opendrug market and high levels of illicit drug use, poverty and HIV infection. Individuals wereeligible to participate in ACCESS if they were aged 18 years or older, were HIV-seropositive, have used illicit drugs other than cannabis in the month prior to enrolment, andprovided written informed consent. Participants were compensated $C20 at each study visit.At baseline and semiannually, participants complete an interviewer-administeredquestionnaire soliciting demographic data, information on drug use patterns, as well as othercharacteristics and exposures. At each of these visits, individuals also undergo anexamination by a study nurse and provide blood samples for serologic analyses. Informationgathered at each interview is augmented by comprehensive information on HIV care andtreatment outcomes from the local centralised HIV/AIDS registry. Specifically, through aconfidential linkage, a complete clinical profile of all CD4 T-cell counts, HIV-1 RNA pVLobservations and exposure to specific antiretroviral agents for each participant are obtained.In British Columbia, all provision of ART is centralised through a province-wide ARTdispensation programme, where ART and related care are provided free of charge. TheACCESS study has been approved by the University of British Columbia/ProvidenceHealthcare Research Ethics Board.Study participantsWe included all individuals who had received at least 1 day of ART at the time of thebaseline interview. Individuals who were ART-naïve at baseline but who initiated treatmentduring follow-up were included from the next follow-up interview forward. As well, to beincluded in these analyses, at least one observation of CD4 cell count and pVL had to becompleted within±180 days of the day they entered the study.Variable selectionThe primary outcome of interest was non-detectable pVL in the previous 6 months, definedas having achieved a HIV-1 RNA load <500 copies/mL plasma (yes vs no). In the event thatmore than one pVL observation was collected within a 6-month follow-up, we used themedian of all the observations, which was then categorised into either having achieved aHIV-1 RNA load <500 copies/mL plasma or not. The primary explanatory variable ofinterest was reporting sex work, defined as the exchange of sex for money, gifts, food,shelter, clothes, drugs, or favours, at any time in the 6-month period prior to the follow-upinterview (yes vs no). This variable was measured longitudinally at each follow-up and itwas included in the analysis as a time-updated measure. To estimate the relationshipbetween sex work and pVL, we considered secondary explanatory variables that maypotentially confound this relationship. These included a range of demographic andsocioeconomic variables, such as age (dichotomised at the median); gender (female vsmale); homelessness (yes vs no); illicit drug use (any illicit injection drug use vs any illicitnon-injection drug use only vs none); binge drug use of illicit drugs by either injection ornon-injection (yes vs no); current enrolment in methadone maintenance therapy (MMT) (yesvs no); and incarceration (yes vs no). We included aboriginal ancestry (yes vs no) as apotential variable of interest given that past research has shown links between aboriginalethnicity and various HIV-related outcomes, including pVL suppression and virologicTi et al. Page 3Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptfailure.13 Homelessness was defined as living on the street or having no fixed address in thelast 6 months. Illicit drug use was considered using a three-level variable where abstinenceconstituted the reference category and was compared to the influence of any injection druguse (ie, heroin, cocaine, or crystal methamphetamine injecting) and illicit non-injection druguse only during the previous 6 months. The illicit injection drug use category could alsoinclude polysubstance users who also used illicit drugs by non-injection routes. All time-varying variables are time-updated and refer to the 6-month period prior to the follow-upinterview unless otherwise indicated. Additionally, we included the following clinicalvariables: year of ART initiation (per year increase); the presence of a protease inhibitor inthe first ART regimen (yes vs no); pVL at ART initiation (copies/mL, log10 transformed);CD4 cell count in the last 6 months (per 100 cells/mL); and HIV physician experience (per100 patients). ART adherence was also included and defined as the quotient of the numberof days that ART was dispensed divided by the total number of days an individual waseligible for ART (determined by the number of days in any period after the first dispensationof ART); this proportion was dichotomised as ≥95% vs <95%. For instance, if an individualwas dispensed 90 days of medications and was eligible for treatment for the entire 180-dayperiod prior to the interview, adherence was 50%. This validated measure using pharmacyrefill data has been used extensively in previous research and has been shown to reliablypredict pVL suppression14 and survival.1Statistical analysesAs a first step, we examined the baseline characteristics of our sample, stratified by whetherparticipants achieved pVL suppression in the 6 months prior to the baseline interview.Categorical variables were analysed using Pearson’s χ2 test and continuous variables wereanalysed using the Wilcoxon Rank-Sum test. Next, we used generalised estimatingequations (GEE) to estimate unadjusted OR for the effect of sex work and all othersecondary explanatory variables on pVL suppression. We used GEE for the analysis ofcorrelated data since the factors potentially associated with pVL suppression during follow-up were time-dependent measures. We only included individuals with complete data at eachgiven time point.To estimate the independent effect of sex work on pVL suppression, we constructed amultivariate GEE model using a variable selection process described previously byMaldonado and Greenland.15 In this process, we employed a conservative p value cutoff≤0.20 to determine which variables were possibly associated with pVL suppression in GEEanalyses described above. Then we fit a full model including these explanatory variables,noting the value of the coefficient associated with sex work. In a stepwise manner, weremoved the secondary explanatory variable corresponding to the smallest relative change inthe effect of sex work on pVL suppression from further consideration. We continued thisiterative process until the maximum change of the value of the coefficient for sex work fromthe full model exceeded 5%. Remaining variables were considered confounders inmultivariate analyses. We have previously used this approach to estimate the independentrelationship of a primary explanatory variable on an outcome of interest8Ti et al. Page 4Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptAs a final step, we conducted a mediation analysis to determine whether adherence to ARTmediated the relationship between sex work and pVL suppression. Two methods were used:the Baron and Kenny approach,16 which involved running two GEE models, one with andone without the adherence variable, to determine whether the sex work variable maintainedits significance after the adherence variable was added, and the Sobel test statistic.17 Thesestatistical tests for mediation have been used previously in other studies.18,19RESULTSBetween May 1996 and May 2012, 622 HIV-seropositive DU met the inclusion criteria forthis analysis. Due to missing observations in the variables of interest, 35 (5.6%) participantswere excluded from the analysis to provide a total of 587 participants in the final analyticsample with a median of 32 months (IQR: 18–60) of prospective follow-up. Among theparticipants, 169 (28.8%) initiated ART during the study period. The sample comprised 186(31.7%) females. Over the study period, the participants contributed 2224 person-years offollow-up. Table 1 shows the baseline characteristics of the study sample stratified by pVLsuppression.Among participants, 91 (15.5%) participants reported sex work at baseline; of these, 17(18.7%) were male. In total, 127 (21.6%) participants reported sex work at least oncesometime during the study period. At baseline, pVL suppression was observed in 275(46.9%) participants and, in total, 492 (83.8%) participants achieved at least one period ofpVL suppression sometime during the study.The crude longitudinal estimates of the odds of pVL suppression are presented in table 2.SW had significantly lower odds of achieving pVL suppression in unadjusted analysiscompared to non-SW (OR=0.50, 95% 95% CI 0.38 to 0.65, p<0.001). Factors associatedwith significantly higher odds of pVL suppression included older age and enrolment inMMT (both p<0.001). Additionally, participants who were women, reported homelessness,injection drug use, binge drug use and incarceration, had lower odds of pVL suppression (allp≤0.010). Among clinical factors, year of ART initiation, ART adherence, CD4 cell countand HIV physician experience were positively associated with higher odds of pVLsuppression, whereas pVL at ART initiation was inversely associated with the outcome (allp≤0.001).As presented in table 3, in the first multivariate model that adjusted for age, gender,homelessness, illicit drug use, enrolment in MMT, pVL at ART initiation and CD4 cellcount, SW had independently lower odds of pVL suppression (adjusted OR (AOR)=0.66;95% CI 0.45 to 0.96). In the second model, when ART adherence was included as anadditional variable, the effect of sex work on pVL suppression was no longer significant(AOR=0.72; 95% CI 0.49 to 1.04), supporting the role of adherence as a mediating variablein the relationship between sex work and pVL suppression. A second test of mediationconfirmed the role of ART adherence as a mediating variable (Sobel test statistic=−2.12,p=0.034).Ti et al. Page 5Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptDISCUSSIONIn the present study, we observed that a large proportion of our participants achieved pVLsuppression, with over 80% of participants experiencing at least one period of pVLsuppression. After controlling for a range of relevant individual, social and structural factors,SW-DU remained at significantly reduced odds of achieving pVL suppression compared tonon-SW-DU. However, this relationship did not persist when ART adherence was includedas a mediating variable. To our knowledge, this study is the first to demonstrate thedramatically reduced rates of pVL suppression among SW-DU, and the role of ARTadherence on virologic response in a setting where there are no financial barriers to HIVtreatment and care.Our study has several limitations that should be noted. First, because of the observationalnature of the ACCESS study, the potential effect of residual confounding must beconsidered when interpreting the effect of adherence and sex work on pVL suppression.Second, our sample was not randomly recruited and, therefore, may not be representative ofall local DU. Third, the study included some data derived from self-report and, thus, may besubject to reporting biases, including socially desirable reporting and recall bias. However,our outcome of interest and ART adherence measures were observed from comprehensiveadministrative records and we do not believe individuals differentially reported engagementin sex work based on pVL or adherence.Local and international research in settings with free ART access have identified an array ofindividual, social and structural barriers to poor adherence and retention among SW,including stigma and discrimination in healthcare settings, lack of support, criminalisation ofsex work and HIV, and geographic mobility.20 ,21 These factors can impede dailymedication regimes and access to conventional ART clinics due to avoidance of police,violent predators or partners, and working late night hours and away from health services.21At the same time, data suggest that where programmes can address these gaps in retention,SW can have the same clinical and biological outcomes as other key affected populations.22Ongoing drug use and poverty may also indirectly prevent SW from achieving optimal ARTadherence.20,21 Given these past findings, our results have important implications for effortsto promote improved HIV treatment outcomes and reduce morbidities for SW-DU, as wellas population-level benefits of increasing universal coverage of HIV treatment to SW.As demonstrated in the present study, poor adherence to ART predictably leads to inferiorpVL suppression. Consequently, increases in HIV-related morbidity and mortality are likelyto occur among SW-DU, in the absence of optimal adherence. In order to improve virologicoutcomes among SW living with HIV, evidence-based interventions aimed at improving thehealth and social conditions of SW are urgently needed. Since much sex work among street-involved populations in this setting involves exchanging sex directly for illicit drugs, andgiven the high rates of untreated addiction among this population, efforts to expand harmreduction and addiction treatment are also urgently needed.In December 2012, new UN guidelines were released on HIV prevention, treatment and careamong SW.23 These guidelines specifically address ART coverage and scale up, and followTi et al. Page 6Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author Manuscriptstandard WHO guidelines for ART for all HIV-positive individuals, with specialconsideration of potential HIV comorbidities (eg, STIs, addiction). Importantly, theseguidelines call on governments, public health and community to address structural barriersto improve access and retention in HIV prevention and ART for SW, including removal ofcriminal and punitive approaches targeting SW, voluntary and non-coercive access to testingand treatment and addressing stigma by health providers and community. In many settingsglobally, obstacles to optimal HIV treatment and care remain despite a large body ofresearch demonstrating the problematic use of criminalising approaches to sex work, druguse and HIV.5,11 For example, studies have shown that the reliance on law enforcementefforts (eg, police crackdowns) in Canada can deter SW-DU from accessing healthservices,24 and thus may subsequently impact their access to, and continued engagement in,ART. Given the substantial burden of HIV among SW and DU in our setting9 as well asothers,11,25 efforts to implement these guidelines and develop strategies to reduce social andstructural barriers to ART adherence and patient retention in care for SW-DU in higher-income settings are urgently needed.Prior studies have documented the value of a multidisciplinary approach to adherencesupport for SW and DU, including close follow-up with a peer health advocate and outreachteam as well as collective support from peer educators, physicians and other healthcareworkers.22,26 Peer and sex work-led models, such as the San Francisco Occupational Healthand Safety clinic,27 and the Songachi model in India,28 have been shown to reduce stigmaand barriers to healthcare and increase trust with service providers that could promoteincreased retention in HIV care. Indeed, a recent study in Vancouver demonstrated apositive impact on adherence and pVL outcomes from implementing a peer-drivenintervention model among SW.26 Other strategies that warrant consideration include mobileand text messaging ART adherence programmes that may be adaptable to SW, givenincreasing use of mobile technologies and high levels of mobility among this population.29To conclude, we analysed the effect of sex work on pVL suppression using data from along-running prospective cohort of HIV-positive DU with free access to ART. Our resultsdemonstrate that SW-DU have a reduced odds of pVL suppression compared to their non-SW-DU counterparts, and that this relationship was mediated by ART adherence. Ourfindings highlight the overall need for strategies to improve HIV care among SW-DU,including peer and sex work-led initiatives to support retention and adherence. Futureresearch should seek to explore factors other than ART adherence that may potentiallymediate the relationship between sex work and pVL suppression. Additionally, furtherresearch that explores why SW-DU may have lower rates of adherence to ART incomparison to other DU will be helpful to inform intervention strategies. Given pastresearch demonstrating the need to improve access to harm reduction and addictiontreatment among this population, efforts to expand evidence-based addiction treatment mustalso be prioritised. Similarly, given past research highlighting how laws criminalising sexwork contribute to barriers to individuals’ safety and access to care, strategies to improveSW safety that can help facilitate improved HIV care must also be prioritised.Ti et al. Page 7Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptAcknowledgmentsThe authors thank the study participants for their contributions to the research, as well as current and pastresearchers and staff. We would specifically like to thank Deborah Graham, Tricia Collingham, Carmen Rock,Brandon Marshall, Caitlin Johnston, Steve Kain, Benita Yip and Jennifer Matthews for their research andadministrative assistance.This work was supported in part by a Tier 1 Canada Research Chair in Inner-City Medicine awarded to EW. Thestudy is supported by the US National Institutes of Health (R01-DA021525). JM is supported by the BritishColumbia Ministry of Health; through an Avant-Garde Award (No. 1DP1DA026182-01) from the National Instituteof Drug Abuse (NIDA), at the US National Institutes of Health (NIH); and through a KT Award from the CanadianInstitutes of Health Research (CIHR). He has also received financial support from the International AIDS Society,United Nations AIDS Program, World Health Organization, National Institutes of Health Research-Office of AIDSResearch, National Institute of Allergy & Infectious Diseases, The United States President’s Emergency Plan forAIDS Relief (PEPfAR), Bill & Melinda Gates Foundation, French National Agency for Research on AIDS & ViralHepatitis (ANRS), the Public Health Agency of Canada, the University of British Columbia, Simon FraserUniversity, Providence Health Care and Vancouver Coastal Health Authority. He has received grants from Abbott,Biolytical, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck and ViiV Healthcare. M-JM is supported by the Michael Smith Foundation for Health Research and the Canadian Institutes of HealthResearch.REFERENCES1. Wood E, Hogg RS, Lima VD, et al. Highly active antiretroviral therapy and survival in HIV-infected injection drug users. JAMA. 2008; 300:550–4. [PubMed: 18677027]2. Wood E, Hogg RS, Yip B, et al. Why are baseline HIV RNA levels 100,000 copies/mL or greaterassociated with mortality after the initiation of antiretroviral therapy? J Acquir Immune DeficSyndr. 2005; 38:289–95. [PubMed: 15735446]3. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviraltherapy. N Engl J Med. 2011; 365:493–505. [PubMed: 21767103]4. World Health Organization. Programmatic update: antiretroviral treatment as prevention (TASP) ofHIV and TB. WHO; Geneva: 2012. http://whqlibdoc.who.int/hq/2012/WHO_HIV_2012.12_eng.pdf5. Wolfe D, Carrieri M, Shepard D. Treatment and care for injecting drug users with HIV infection: Areview of barriers and ways forward. Lancet. 2010; 376:355–66. [PubMed: 20650513]6. Malta M, Strathdee SA, Magnanini MMF, et al. Adherence to antiretroviral therapy for humanimmunodeficiency virus/acquired immune deficiency syndrome among drug users: a systematicreview. Addiction. 2008; 103:1242–57. [PubMed: 18855813]7. Milloy M-J, Kerr T, Bangsberg DR, et al. Homelessness as a structural barrier to effectiveantiretroviral therapy among HIV-seropositive illicit drug users in a Canadian setting. AIDS PatientCare STDS. 2012; 26:60–7. [PubMed: 22107040]8. Milloy M-J, Kerr T, Buxton J, et al. Dose-response effect of incarceration events on nonadherenceto HIV antiretroviral therapy among injection drug users. J Infect Dis. 2011; 203:1215–21.[PubMed: 21459814]9. Wood E, Schachar J, Li K, et al. Sex trade involvement is associated with elevated HIV incidenceamong injection drug users in Vancouver. Addict Res Theory. 2007; 15:321–5.10. Kral AH, Bluthenthal RN, Lorvick J, et al. Sexual transmission of HIV-1 among injection drugusers in San Francisco, USA: risk-factor analysis. Lancet. 2001; 357:1397–401. [PubMed:11356437]11. Baral S, Beyrer C, Muessig K, et al. Burden of HIV among female sex workers in low-income andmiddle-income countries: a systematic review and meta-analysis. 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Access and utilization of HIV treatment and services amongwomen sex workers in Vancouver’s downtown eastside. J Urban Health. 2005; 82:488–97.[PubMed: 15944404]22. Huet C, Ouedraogo A, Konaté I, et al. Long term virological, immunological and mortalityoutcomes in a cohort of HIV-infected female sex workers treated with highly active antiretroviraltherapy in Africa. BMC Public Health. 2011; 11:700. [PubMed: 21917177]23. World Health Organization. United Nations Population Fund. Joint United Nations Programme onHIV/AIDS. et al. Prevention and treatment of HIV and other sexually transmitted infections forsex workers in low- and middle-income countries: recommendations for a public health approach.World Health Organization; Geneva: 2012. http://apps.who.int/iris/bitstream/10665/77745/1/9789241504744_eng.pdf24. Shannon K, Rusch M, Shoveller J, et al. Mapping violence and policing as an environmental–structural barrier to health service and syringe availability among substance-using women instreet-level sex work. Int J Drug Policy. 2008; 19:140–7. [PubMed: 18207725]25. Mathers BM, Degenhardt L, Phillips B, et al. Global epidemiology of injecting drug use and HIVamong people who inject drugs: a systematic review. Lancet. 2008; 372:1733–45. [PubMed:18817968]26. Deering K, Shannon K, Sinclair H, et al. Piloting a peer-driven intervention model to increaseaccess and adherence to antiretroviral therapy and HIV care among street-entrenched HIV-positivewomen in Vancouver. AIDS Patient Care STDS. 2009; 23:603–9. [PubMed: 19591602]27. Cohan D, Lutnick A, Davidson P, et al. Sex worker health: San Francisco style. Sex Transm Infect.2006; 82:418–22. [PubMed: 16854996]28. Cohen J. Sonagachi sex workers stymie HIV. Science. 2004; 304:506. [PubMed: 15105470]29. Lester RT, Ritvo P, Mills EJ, et al. Effects of a mobile phone short message service onantiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Lancet. 2010;376:1838–45. [PubMed: 21071074]Ti et al. Page 9Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptKey messages• Among a cohort of HIV-positive people who use illicit drugs (DU), sex workwas negatively associated with plasma HIV-1 RNA viral load (pVL)suppression.• Adherence to antiretroviral therapy (ART) mediated the relationship betweensex work and pVL suppression.• Evidence-based interventions to improve adherence to ART among sex workerswho use illicit drugs (SW-DU) are urgently needed.• There is a need for strategies to improve HIV care among SW-DU, includingpeer and sex work-led initiatives to support retention and adherence.Ti et al. Page 10Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptTi et al. Page 11Table 1Baseline characteristics of ART-exposed DU in Vancouver, Canada, stratified by pVL suppression in the last 6 months (n=587)Viral load suppressionCharacteristicTotal (%) (n=587)Yes (%) (n=275)No (%) (n=312)p ValueSex work*91 (15.5)30 (10.9)61 (19.6)0.004≥43 years old268 (45.7)170 (61.8)98 (31.4)<0.001Female gender186 (31.7)65 (23.6)121 (38.8)<0.001Aboriginal ancestry214 (36.5)90 (32.7)124 (39.7)0.078Homelessness*143 (24.4)53 (19.3)90 (28.9)0.007Illicit drug use* Any injection drug use443 (75.5)184 (66.9)259 (83.0)<0.001 Any illicit drug use109 (18.6)79 (28.7)30 (9.6)<0.001Binge drug use*320 (54.5)141 (51.3)179 (57.4)0.139Current enrolment in MMT211 (36.0)106 (38.6)105 (33.7)0.218Incarceration*76 (13.0)26 (9.5)50 (16.0)0.018Year of ART initiation (per year) (med, IQR)2000 (1997–2006)2002 (1997–2007)1998 (1996-2006)<0.001≥95% ART adherence325 (55.4)207 (75.3)118 (37.8)<0.001PI in first regimen240 (40.9)112 (40.7)128 (41.0)0.942pVL at ART initiation (per loglO) (med, IQR)2.56 (1.65–4.30)1.65 (1.54–1.69)4.11 (2.98–4.87)<0.001CD4 cell count (per 100 cells)*  (med, IQR)3.20 (1.93–4.50)3.77 (2.53–4.90)2.64 (1.47–4.00)<0.001HIV physician experience (per 100 patients) (med, IQR)0.44 (0.11–1.26)0.58 (0.17–1.53)0.30 (0.09–0.94)<0.001*Refers to the 6-month period prior to the interview.ART, antiretroviral therapy; DU, people who use illicit drugs; MMT, methadone maintenance therapy; PI, protease inhibitor; pVL, plasma viral load.Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptTi et al. Page 12Table 2Bivariate GEE analysis off actors associated with pVL suppression in the last 6 months among ART-exposedDU in Vancouver, Canada (n=587)Characteristic Crude OR (95% CI) p ValueSex work* (yes vs no) 0.50 (0.38 to 0.65) <0.001Median age (≥median vs <median) 3.63 (2.75 to 4.80) <0.001Gender (female vs male) 0.53 (0.41 to 0.69) <0.001Aboriginal ancestry (yes vs no) 0.85 (0.66 to 1.10) 0.229Homelessness* (yes vs no) 0.54 (0.45 to 0.66) <0.001Illicit drug use* Any injection drug use 0.45 (0.33 to 0.61) <0.001 Any illicit drug use 1.07 (0.75 to 1.54) 0.703 None 1.00 (reference)Binge drug use* (yes vs no) 0.87 (0.76 to 0.98) 0.027Current enrolment in MMT (yes vs no) 2.14(1.61 to 2.83) <0.001Incarceration* (yes vs no) 0.59 (0.48 to 0.71) <0.001Year of ART initiation (per year increase) 1.08 (1.05 to 1.11) <0.001ART adherence (≥95% vs <95%) 8.84 (7.22 to 10.83) <0.001PI in first regimen (yes vs no) 1.11 (0.86 to 1.44) 0.424pVL at ART initiation (per Iog 10 increase) 0.44 (0.40 to 0.48) <0.001CD4 cell count* (per 100 cells) 1.48 (1.36 to 1.62) <0.001HIV physician experience (per 1000 patients) 1.28 (1.11 to 1.47) <0.001*Refers to the 6-month period prior to the interview.ART, antiretroviral therapy; DU, people who use illicit drugs; GEE, generalised estimating equations; MMT: methadone maintenance therapy; PI:protease inhibitor; pVL, plasma viral load.Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.NIH-PA Author ManuscriptNIH-PA Author ManuscriptNIH-PA Author ManuscriptTi et al. Page 13Table 3Adjusted ORs highlighting the effect of sex work on pVL suppression in GEE models (n=587)Model Adjusted OR(95% CI)p ValueModel 1.Effect of sex work, without adherence(mediator) variable included*0.66 (0.45 to 0.%) 0.031Model 2.Effect of sex work, includingadherence (mediator) variable*0.72 (0.49 to 1.04) 0.080*Adjusted for age, gender, homelessness, injection drug use, enrolment in methadone maintenance therapy, pVL at ART initiation, and CD4 cellcount.ART, antiretroviral therapy; GEE, generalised estimating equation; pVL, plasma viral load.Sex Transm Infect. Author manuscript; available in PMC 2015 August 01.

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