@prefix vivo: . @prefix edm: . @prefix ns0: . @prefix dcterms: . @prefix skos: . vivo:departmentOrSchool "Medicine, Faculty of"@en, "Other UBC"@en, "Non UBC"@en ; edm:dataProvider "DSpace"@en ; ns0:identifierCitation "BMC Infectious Diseases. 2016 Oct 21;16(1):590"@en ; dcterms:contributor "British Columbia Centre for Excellence in HIV/AIDS"@en ; ns0:rightsCopyright "The Author(s)."@en ; dcterms:creator "Tanner, Zachary"@en, "Lachowsky, Nathan"@en, "Ding, Erin"@en, "Samji, Hasina"@en, "Hull, Mark W."@en, "Cescon, Angela"@en, "Patterson, Sophie"@en, "Chia, Jason"@en, "Leslie, Alia"@en, "Raboud, Janet"@en, "Loutfy, Mona"@en, "Cooper, Curtis"@en, "Klein, Marina"@en, "Machouf, Nima"@en, "Tsoukas, Christos"@en, "Montaner, Julio"@en, "Hogg, Robert S."@en ; dcterms:issued "2017-12-18T20:19:32Z"@en, "2016-10-21"@en ; dcterms:description """Background: Gay, bisexual and other men who have sex with men (MSM) are disproportionately affected by HIV in Canada. Combination antiretroviral therapy has been shown to dramatically decrease progression to AIDS, premature death and HIV transmission. However, there are no comprehensive data regarding combination antiretroviral therapy outcomes among this population. We sought to identify socio-demographic and clinical correlates of viral suppression and rebound. Methods: Our analysis included MSM participants in the Canadian Observational Cohort, a multi-site cohort of HIV-positive adults from Canada’s three most populous provinces, aged ≥18 years who first initiated combination antiretroviral therapy between 2000 and 2011. We used accelerated failure time models to identify factors predicting time to suppression (2 measures <50 copies/mL ≥30 days apart) and subsequent rebound (2 measures >200 copies/mL ≥30 days apart). Results: Of 2,858 participants, 2,448 (86 %) achieved viral suppression in a median time of 5 months (Q1–Q3: 3–7 months). Viral suppression was significantly associated with later calendar year of antiretroviral therapy initiation, no history of injection drug use, lower baseline viral load, being on an initial regimen consisting of non-nucleoside reverse-transcriptase inhibitors, and older age. Among those who suppressed, 295 (12 %) experienced viral rebound. This was associated with earlier calendar year of antiretroviral therapy initiation, injection drug use history, younger age, higher baseline CD4 cell count, and living in British Columbia. Conclusions: Further strategies are required to optimize combination antiretroviral therapy outcomes in men who have sex with men in Canada, specifically targeting younger MSM and those with a history of injection drug use."""@en ; edm:aggregatedCHO "https://circle.library.ubc.ca/rest/handle/2429/64080?expand=metadata"@en ; skos:note "RESEARCH ARTICLE Open AccessPredictors of viral suppression and reboundamong HIV-positive men who have sexi-site Canadianhistory of injection drug use, lower baseline viral load, being on an initial regimen consisting of non-nucleosideTanner et al. BMC Infectious Diseases (2016) 16:590 DOI 10.1186/s12879-016-1926-z6Faculty of Health Sciences, Simon Fraser University, Vancouver, CanadaFull list of author information is available at the end of the article* Correspondence: robert_hogg@sfu.ca; bobhogg@cfenet.ubc.ca1BC Centre for Excellence in HIV/AIDS, Vancouver, CanadaKeywords: Canada, HIV, MSM, Viral load, Suppression, Reboundreverse-transcriptase inhibitors, and older age. Among those who suppressed, 295 (12 %) experienced viralrebound. This was associated with earlier calendar year of antiretroviral therapy initiation, injection drug usehistory, younger age, higher baseline CD4 cell count, and living in British Columbia.Conclusions: Further strategies are required to optimize combination antiretroviral therapy outcomes in men whohave sex with men in Canada, specifically targeting younger MSM and those with a history of injection drug use.cohortZachary Tanner1, Nathan Lachowsky1,2,3, Erin Ding1, Hasina Samji1, Mark Hull1,4, Angela Cescon5,Sophie Patterson1,6, Jason Chia1, Alia Leslie1, Janet Raboud7,8, Mona Loutfy7,9,10,11, Curtis Cooper12,Marina Klein13,14, Nima Machouf15, Christos Tsoukas13, Julio Montaner1,4, and Robert S. Hogg1,6,16*for the Canadian Observation Cohort (CANOC) CollaborationAbstractBackground: Gay, bisexual and other men who have sex with men (MSM) are disproportionately affected by HIV inCanada. Combination antiretroviral therapy has been shown to dramatically decrease progression to AIDS, prematuredeath and HIV transmission. However, there are no comprehensive data regarding combination antiretroviral therapyoutcomes among this population. We sought to identify socio-demographic and clinical correlates of viral suppressionand rebound.Methods: Our analysis included MSM participants in the Canadian Observational Cohort, a multi-site cohortof HIV-positive adults from Canada’s three most populous provinces, aged ≥18 years who first initiated combinationantiretroviral therapy between 2000 and 2011. We used accelerated failure time models to identify factorspredicting time to suppression (2 measures <50 copies/mL ≥30 days apart) and subsequent rebound(2 measures >200 copies/mL ≥30 days apart).Results: Of 2,858 participants, 2,448 (86 %) achieved viral suppression in a median time of 5 months (Q1–Q3: 3–7months). Viral suppression was significantly associated with later calendar year of antiretroviral therapy initiation, nowith men in a large mult© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Tanner et al. BMC Infectious Diseases (2016) 16:590 Page 2 of 11BackgroundGay, bisexual and other men who have sex with men(MSM) have the highest prevalence of HIV in Canada[1]. Between 1985 and 2011, 54.7 % of diagnosed HIVcases with known exposure status in Canada were attrib-utable to MSM (n = 69,856), even though self-identifiedMSM comprise only an estimated 2.1 % of the Canadianpopulation [1, 2]. In the first two decades of the epi-demic, this disproportionate burden was characterizedby premature mortality across MSM communities [3],with the estimated life expectancy of gay men in someurban environments being 8 to 20 years less than that ofthe general male population [4]. Since the implementa-tion of combination antiretroviral therapy (cART),people living with HIV/AIDS (PHAs) have experiencedsignificant improvements in health outcomes and cannow achieve life expectancy near that of the generalpopulation [5–7]. High levels of adherence to cART,usually defined as taking >95 % of prescribed medication[8], usually results in full suppression of HIV-1-RNAlevels in plasma, markedly improving health outcomesand similarly reducing the risk of HIV transmission [9].Adherent patients generally achieve viral suppression be-tween 8 and 24 weeks after initiating treatment [10].Despite the proven clinical benefits of cART, CanadianMSM continue to experience a sustained rate of newHIV infections compared with the general population [1,11]. A myriad of factors, including the heightened risk ofinfection via anal sex compared with vaginal sex [12];behavioural factors, such as condomless anal intercourseand substance use [13]; and social factors, includinghomophobia, stigma, and social exclusion [11, 12, 14]have been advanced to explain these high rates of newinfections. Additionally, structural barriers such ascriminalization of HIV exposure [15], insufficient accessto culturally appropriate health services and distrust ofavailable health care providers [16–18], may deter someMSM from seeking HIV testing and treatment, as wellas negatively impact retention rates. Continuation oftreatment is crucial for long-term clinical success andprevention of viral rebound [19]. Failure to remain vir-ally suppressed increases the risk of poor health out-comes, such as HIV drug resistance, progression toAIDS, premature death, and HIV transmission [20, 21].While risk factors for HIV seroconversion amongMSM have been largely explored, there is a sizable re-search gap regarding modern-day cART treatment re-sponses. To date, there has not been an analysis of theclinical and social circumstances associated with viro-logic outcomes among MSM in Canada. The PublicHealth Agency of Canada has specifically identified thisknowledge gap [1]. Furthermore, viral suppression is aprincipal component of the new UN 90-90-90 Target(i.e., to achieve 90 % of PHA diagnosed globally, 90 % ofthem on treatment, 90 % of them on cART virally sup-pressed by 2020) [22]. This ambitious plan to end AIDSas a global pandemic provides a timely and pertinentframework for assessing where Canadian MSM on cARTstand with regard to this target. The purpose of thisstudy was to identify socio-demographic and clinicalcorrelates of treatment response among MSM inCanada, as measured by viral suppression and subse-quent virologic rebound. This will help inform cART re-tention strategies for MSM living with HIV.MethodsStudy populationThe Canadian Observational Cohort (CANOC) collabor-ation is an observational cohort study of antiretroviral-naïve HIV-positive individuals initiating cART after 1January 2000 [23]. This multi-site study is comprised ofeight cohorts located in BC, Quebec, and Ontario. Al-most half of the estimated 20,500 HIV-positive individ-uals on cART in these three provinces are representedwithin CANOC [24]. Patient eligibility criteria for inclu-sion in CANOC are: documented HIV infection, resi-dence in Canada, aged 18 years or older, initiation of afirst antiretroviral regimen comprised of at least threeindividual agents, and at least one measurement of HIVplasma viral load and CD4 T-cell count within one yearof initiating cART. Patient selection and data extractionare performed locally at the data centres of the partici-pating cohort sites. Demographic, laboratory, and clin-ical data from each cohort are then pooled and analysedat the Data Coordinating Centre in Vancouver, BC. Forthis analysis, we focused exclusively on males, excludingmen with missing or unknown data regarding MSM sta-tus. We also excluded individuals who did not have atleast two viral load measurements within one year afterinitiating cART, as well as those with less than one yearof follow-up. The date of administrative censoring forthis analysis was 31 December 2012.The human subjects activities of CANOC were ap-proved by the Simon Fraser University Research EthicsBoard, the University of British Columbia Research Eth-ics Board and the following local institutional reviewboards of the participating cohorts: Providence HealthCare Research Institute Office of Research Services, TheOttawa Hospital Research Ethics Board, UniversityHealth Network (UHN) Research Ethics Board, VéritasInstitutional Review Board (IRB), Biomedical C (BMC)Research Ethics Board of the McGill University HeathCentre (MUHC), University of Toronto HIV ResearchEthics Board (HIV REB), and Women’s College HospitalResearch Ethics Board.Local cohort studies have obtained written consent ex-cept for the following: HAART Observational MedicalEvaluation and Research (IRB approves the retrospectiveTanner et al. BMC Infectious Diseases (2016) 16:590 Page 3 of 11use of anonymous administrative data without requiringconsent; an information sheet for participants is pro-vided in lieu of a consent form); Ottawa Hospital Cohort(IRB approves the anonymous use of data retrospectivelyabstracted from clinical care databases without requiringconsent); UHN (REB approves the anonymous use ofdata retrospectively abstracted from clinical care data-bases without requiring consent); MUHC (IRB approvesthe anonymous use of data retrospectively abstractedfrom clinical care databases without requiring consent;patients sign a general waiver on opening a medicalchart at the hospital but no specific study related con-sent); Maple Leaf Medical Clinic (REB has approved theanonymous use of data retrospectively abstracted fromclinical care databases without requiring consent); andEffective Anti-Retroviral Therapy cohort (REB approvesthe anonymous use of data retrospectively abstractedfrom clinical care databases without requiring consent;patients sign a general waiver on opening a medicalchart at the hospital but no specific study relatedconsent).Further details on the collaborating cohorts and gen-eral CANOC structure are available [23].OutcomesViral suppression after cART initiation was defined asthe time to the first of at least two consecutive plasmaHIV RNA measurements below 50 copies/mL, at least30 days apart in the first year of treatment. We definedsuppression within one year to focus on more timely vi-rologic control [25]. Viral rebound was only measuredamong MSM who achieved viral suppression within thefirst year of treatment. Rebound was defined as the timeto the first of at least two consecutive VL measuresabove 200 copies/mL, at least 30 days apart.Statistical methodsDemographic and clinical characteristics at treatmentinitiation (baseline) were summarized using frequenciesand proportions for categorical variables and mediansand interquartile ranges (Q1–Q3) for continuous vari-ables. Demographic and clinical characteristics of partic-ipants who achieved viral suppression within one year ordid not achieve viral suppression within a year werecompared using Chi-square tests for categorical variablesand Wilcoxon Rank Sum tests for continuous variables.Univariate accelerated failure time models with inter-val censoring were used to explore the association be-tween covariates and each of the two outcomes.Covariates of interest included province of residence,race/ethnicity, age, baseline CD4 cell count, baselineviral load, history of injection drug use (IDU), baselinediagnosis of an AIDS-defining illness (ADI), era of cARTinitiation (i.e., 2000–2003, 2004–2007, 2008–2012), andthird ARV class (i.e., NNRTI, boosted PI, unboosted PI,other). Calendar time of reaching viral suppression wasalso explored as a covariate in the rebound analysis be-cause of its potential influence on subsequent rebound[26]. An exploratory model selection process based onAkaike Information Criterion (AIC), type III p-values,and a priori information was pursued to select variablesfor the multivariable accelerated failure time modelsexamining time to viral suppression and rebound. Thetime origins were the first antiretroviral start date andthe date of the first of two consecutive viral load mea-surements below 50 copies/mL and above 200 copies/mL,for the suppression and rebound models, respectively. Themultivariable models were fitted to an exponential distribu-tion. All analyses were performed using SAS statistical soft-ware, version 9.3 (SAS Institute, Cary, NC).ResultsBaseline demographic and clinical characteristics of thestudy participants are listed in Table 1. Drawing onCANOC data from 2000 to 2011, 3,375 male partici-pants were identified as MSM. 214 of these participantsdid not have at least two viral load measurements withinone year after initiating cART, and another 303 partici-pants had less than one year of follow-up. These partici-pants were excluded from analysis, leaving a total of2,858 men who met the eligibility criteria. By province,30 % of participants were from BC, 37 % were from On-tario, and 34 % were from Quebec. The median follow-up time was 5.0 years (Q1–Q3: 3.0–8.1 years). Therewere 192 (7 %) participants lost to follow-up (defined asno contact for 18+ months), and 122 (4 %) died duringfollow-up. The median age of all participants was40 years (Q1–Q3: 34–46 years). Among 1,441 partici-pants with available ethnicity data, 1,320 (92 %) identi-fied as White, 51 (4 %) as Black, and 70 (5 %) asAboriginal. The median baseline CD4 count was 230cells/mm3 (Q1–Q3: 130–321 cells/mm3) and the medianbaseline viral load was 4.96 log10 copies/mL (Q1–Q34.51–5.00 log10 copies/mL). Of the 2,744 participantswith available hepatitis C (HCV) testing data, 331 (12 %)were seropositive. Additionally, 247 (9 %) participantshad a history of IDU at the time of HIV diagnosis. Atbaseline, 459 (16 %) participants had been diagnosedwith an ADI at or prior to cART initiation. The medianrate of viral load testing was 4 tests per year (Q1–Q3:3–5 tests).Table 2 highlights characteristics associated with MSMachieving at least two consecutive plasma HIV RNAmeasurements below 50 copies/mL, at least 30 daysapart in the first year of treatment. At noted here, 2,448(86 %) MSM participants achieved viral suppressionwithin 12 months of cART initiation. The median timeto suppression was 5 months (Q1–Q3: 3–7 months). OfTable 1 Characteristics of MSM study participants at enrolmentinto CANOC (n = 2858)Characteristic Total (%)aProvinceBritish Columbia 854 (30)Ontario 1045 (37)Quebec 959 (34)Age (years) 40 (34–46)EthnicityCaucasian 1320 (46)Black 51 (2)Aboriginal 70 (2)Other 371 (13)Unknown 1046 (37)History of IDUNo 2555 (89)Yes 247 (9)Unknown 56 (2)Hepatitis C statusNo 2413 (84)Yes 331 (12)Unknown 114 (4)Era of cART initiation2000–2003 729 (26)2004–2007 931 (33)2008–2012 1198 (42)Number of viral load tests per yearLess than 3 583 (20)3–4 1590 (56)5–6 360 (13)More than 6 325 (11)Initial 3rd ARV classNNRTI 1277 (45)Unboosted PI 128 (4)Boosted PI 1239 (43)Other 214 (7)Initial 3rd ARVNevirapine 252 (9)Efavirenz 1033 (36)Lopinavir 424 (15)Atazanavir 578 (20)Other 571 (20)NRTI combinationTenofovir/emtricitabine 1217 (43)Zidovudine/lamivudine 594 (21)Tenofovir/lamivudine 207 (7)Tanner et al. BMC Infectious Diseases (2016) 16:590 Page 4 of 11these 2,448 individuals, 295 (12 %) experienced a subse-quent rebound above 200 HIV RNA copies/mL.In bivariate analysis, time to viral suppression was signifi-cantly associated with IDU history (p < 0.001), calendar yearof cART initiation (p < 0.001), initial composition of ARVregimen (p < 0.001), baseline viral load (p < 0.001), baselineCD4 count (p = 0.001), HCV co-infection (p = 0.001), age(p = 0.002), ethnicity (p = 0.002), having an ADI at baseline(p = 0.006), and province of residence (p = 0.011).Tables 3 and 4 present the univariate and multivariableresults of the accelerated failure time suppression andrebound models. In adjusted multivariable analysis,MSM who experienced viral suppression within one yearof treatment initiation were more likely to have initiatedTable 1 Characteristics of MSM study participants at enrolmentinto CANOC (n = 2858) (Continued)Abacavir/lamivudine 468 (16)Stavudine/lamivudine 212 (7)Other 160 (6)AIDS-defining illnessNo 2284 (80)Yes 459 (16)Unknown 115 (4)Viral load (log10 copies/mL) 4.96 (4.51–5.00)CD4 count (cells/uL) 230 (130–321)ARV antiretroviral, IDU injecting drug use, NNRTI nonnucleoside reversetranscriptase inhibitor, PI protease inhibitoraResults are presented as n (%) with the exception of age, viral load, and CD4count, for which median (Q1–Q3) is shown. Percentages may not equal 100 %as a result of roundingcART from 2004 to 2007 [adjusted hazard ratio (aHR)1.26, 95 % confidence interval (CI) 1.11–1.42] and2008–2012 [aHR 1.32, 95 % CI 1.17–1.48] comparedwith 2000–2003, and to be older [aHR 1.08 per decade,95 % CI 1.03–1.13]. MSM who achieved suppressed viralloads were less likely to have an IDU history [aHR 0.71,95 % CI 0.60–0.85], higher baseline viral load [aHR 0.73per log10 copies/mL, 95 % CI 0.66–0.80], and anunboosted PI [aHR 0.60, 95 % CI 0.48–0.76] or boostedPI [aHR 0.81, 95 % CI 0.74–0.90] containing cART regi-men (Table 3). The multivariable accelerated failure timemodel for viral rebound found that MSM who experi-enced a viral rebound were more likely to be younger[aHR 0.70 per decade, 95 % CI 0.62–0.80], to have anIDU history [aHR 2.52, 95 % CI 1.82–3.50], a higherCD4 cell count at baseline [aHR 1.13 per 100 cells/mm3,95 % CI 1.05–1.22], and less likely to have initiatedcART from 2004 to 2007 [aHR 0.69, 95 % CI 0.53–0.91]or 2008–2012 [aHR 0.43, 95 % CI 0.30–0.61], and to beliving in Ontario [aHR 0.50, 95 % CI 0.38–0.67] or Que-bec [aHR 0.51, 95 % CI 0.38–0.69] (Table 4).Table 2 Characteristics associated with MSM achieving viralsuppression in the first year of treatmentCharacteristic Viral Suppression , n (%)No (n = 410) Yes (n = 2448) P-valueProvinceBritish Columbia 140 (34) 714 (29) 0.011Ontario 158 (39) 887 (36)Quebec 112 (27) 847 (35)Age (years) 38 (33–44) 40 (34–46) 0.002EthnicityCaucasian 216 (53) 1104 (45) 0.002Black 8 (2) 43 (2)Aboriginal 17 (4) 53 (2)Other 40 (10) 331 (14)Unknown 129 (31) 917 (37)History of IDUNo 336 (82) 2219 (91) <0.001Yes 60 (15) 187 (8)Unknown 14 (3) 42 (2)Hepatitis C statusNo 321 (78) 2092 (85) 0.001Yes 68 (17) 263 (11)Unknown 21 (5) 93 (4)Era of cART initiation2000–2003 152 (37) 577 (24) <0.0012004–2007 127 (31) 804 (33)2008–2012 131 (32) 1067 (44)Number of viral load tests per yearLess than 3 115 (28) 468 (19) <0.0013–4 188 (46) 1402 (57)5–6 48 (12) 312 (13)More than 6 59 (14) 266 (11)Initial 3rd ARV classNNRTI 140 (34) 1137 (46) <0.001Unboosted PI 39 (10) 89 (4)Boosted PI 194 (47) 1045 (43)Other 37 (9) 177 (7)Initial 3rd ARVNevirapine 41 (10) 211 (9) <0.001Efavirenz 105 (26) 928 (38)Lopinavir 73 (18) 351 (14)Atazanavir 79 (19) 499 (20)Other 112 (27) 459 (19)Tanner et al. BMC Infectious Diseases (2016) 16:590 Page 5 of 11DiscussionClose to 90 % of HIV-positive MSM receiving cART inCANOC achieved viral suppression within a median of5 months of initiating treatment [27]. However, nearlyone-in-eight HIV-positive MSM who achieved viral sup-pression on cART experienced viral rebound at somepoint following suppression during follow-up. This is thelargest longitudinal, multi-provincial analysis of HIVtreatment responses among MSM in Canada and dem-onstrates that MSM are close to UNAIDS’ proposed tar-gets that 90 % of individuals on cART achieve viralsuppression. This high rate suppression will ensure theTable 2 Characteristics associated with MSM achieving viralsuppression in the first year of treatment (Continued)NRTI combinationTenofovir/emtricitabine 134 (33) 1083 (44) <0.001Zidovudine/lamivudine 114 (28) 480 (20)Tenofovir/lamivudine 27 (7) 180 (7)Abacavir/lamivudine 58 (14) 410 (17)Stavudine/lamivudine 43 (10) 169 (7)Other 34 (8) 126 (5)AIDS-defining illnessNo 307 (75) 1977 (81) 0.006Yes 88 (21) 371 (15)Unknown 15 (4) 100 (4)Viral load (log10 copies/mL) 5.00 (4.75–5.00) 4.93 (4.48–5.00) <0.001CD4 count (cells/uL) 190 (100–310) 231 (134–327) 0.001long-term health of these men and limit new infectionsin this population.The proportion of MSM achieving suppression inCANOC is similar to other studies from several inter-national settings where the HIV burden is also predom-inantly concentrated among MSM. A large NorthAmerican cohort study found that between 2001 and2009, the cumulative incidence of 1-year viral suppres-sion was 84 %, observing that MSM participants had ahigher likelihood of achieving suppression comparedwith other male participants [25]. Between 2010 and2012 in Australia, it was estimated that the proportionof HIV-positive MSM on cART with undetectable viralloads increased from 85 to 90 % [28]. Surveillance datafrom the United Kingdom (UK) suggests that 89 % ofMSM who initiated cART in 2009 were virally sup-pressed by 2010 [29]. Unfortunately these internationalviral suppression estimates for large HIV-positive MSMpopulations do not provide follow-up regarding episodesof subsequent rebound. But, in a large UK-based cohortstudy of previously antiretroviral naïve PHA on cART, ofwhich approximately half were MSM, 11 % experiencedh tovalTanner et al. BMC Infectious Diseases (2016) 16:590 Page 6 of 11Table 3 Accelerated failure time models of factors associated witUnadjusted hazard rati(95 % confidence interProvinceBritish Columbia 1.00Ontario 1.04 (0.93–1.15)Quebec 1.19 (1.07–1.32)Baseline age (per 10 year increment) 1.06 (1.02–1.11)EthnicityCaucasian 1.00Black 0.97 (0.68–1.39)rebound [30], which is a similar proportion to MSMwho experienced rebound in our analysis.Consistent with previous research [31], our analysisfound more recent calendar year of cART initiation topredict better treatment response within a large HIV-positive cohort. This may partially be explained by thesimple fact that ARV regimens in more recent yearshave enhanced drug efficacy and reduced side effects,promoting more optimal treatment response. As part ofour analysis, we also stratified antiretroviral regimens byera of cART initiation and found that in earlier calendaryears, a significantly (p < 0.001) higher proportion of par-ticipants initiated treatment comprised of a Zidovudineand Lamivudine NRTI fixed combination (51, 23, and1 % of participants from 2000 to 2003, 2004 to 2007,Aboriginal 0.75 (0.55–1.01)Other 1.23 (1.07–1.40)Unknown 1.13 (1.03–1.25)History of IDUNo 1.00Yes 0.70 (0.60–0.83)Unknown 0.63 (0.44–0.89)Era of cART initiation2000–03 1.002004–07 1.24 (1.11–1.39)2008–12 1.42 (1.27–1.58)Initial 3rd ARV classNNRTI 1.00Unboosted PI 0.53 (0.42–0.67)Boosted PI 0.82 (0.75–0.90)Other 0.81 (0.67–0.97)Baseline AIDS-defining illnessNo 1.00Yes 0.84 (0.74–0.94)Unknown 1.04 (0.84–1.29)Baseline viral load (per log10 copies/mL) 0.73 (0.66–0.80)Baseline CD4 count (per 100 cells/mm3) 1.04 (1.02–1.07)ime to viral suppression among MSM)P-value Adjusted hazard ratio(95 % confidence interval)P-value0.004 1.00 0.1260.98 (0.88–1.10)1.09 (0.98–1.22)0.007 1.08 (1.03–1.13) 0.0010.001and 2009 to 2012, respectively). In contrast, the better-tolerated and more effective [32] Tenofovir and Emtrici-tabine fixed-dose regimen was the predominant baselineNRTI combination in later calendar years (0, 25, and82 % of participants initiating cART from 2000 to 2003,2004 to 2007, and 2009 to 2012, respectively). Further-more, in terms of ARV drug class, regimens comprisedof NNRTIs were more effective than either boosted orunboosted PI-based for the treatment of patients withno previous exposure to antiretroviral therapy. This iscongruous with a meta-analysis examining ARV regi-mens among HIV-infected patients with limited or noprevious exposure to antiretroviral therapy [33]. NNRTIswere also most prevalent in more recent calendar years,with 49, 33, and 51 % of participants initiating a regimen<0.001 1.00 <0.0010.71 (0.60–0.85)0.71 (0.50–1.02)<0.001 1.00 <0.0011.26 (1.11–1.42)1.32 (1.17–1.48)<0.001 1.00 <0.0010.60 (0.48–0.76)0.81 (0.74–0.90)0.83 (0.69–1.00)0.011<0.001 0.73 (0.66–0.80) <0.001<0.001h tovalTanner et al. BMC Infectious Diseases (2016) 16:590 Page 7 of 11Table 4 Accelerated failure time models of factors associated witUnadjusted hazard rati(95 % confidence interProvinceBritish Columbia 1.00Ontario 0.54 (0.42–0.71)Quebec 0.48 (0.36–0.64)Baseline age (per 10 year increment) 0.75 (0.66–0.86)EthnicityCaucasian 1.00Black 1.35 (0.60–3.06)comprised of NNRTIs from 2000 to 2003, 2004 to 2007,and 2009 to 2012, respectively. More frequent reboundepisodes, especially in British Columbia and in earliercalendar years, may also reflect physician-recommendedstructured treatment interruptions, which were morecommon during earlier cART eras and in BritishColumbia [34].The low median baseline CD4 cell count among par-ticipants (230 cells/mm3) is concerning, although guide-lines for the timing of cART initiation have changedsignificantly over the period of study. The median base-line CD4 cell count increased throughout the studytimeline, likely in response to these updated guidelines.In 2000, the median baseline CD4 cell count among allAboriginal 1.67 (0.93–3.00)Other 0.98 (0.70–1.38)Unknown 0.67 (0.51–0.89)History of IDUNo 1.00Yes 2.67 (1.96–3.64)Unknown 2.02 (1.04–3.93)Era of cART initiation2000–03 1.002004–07 0.71 (0.56–0.92)2008–12 0.49 (0.35–0.69)Initial 3rd ARV classNNRTI 1.00Unboosted PI 1.60 (0.99–2.59)Boosted PI 1.16 (0.91–1.49)Other 1.53 (1.01–2.31)Baseline AIDS-defining illnessNo 1.00Yes 0.99 (0.73–1.34)Unknown 1.00 (0.58–1.72)Baseline viral load (per log10 copies/mL) 1.11 (0.85–1.45)Baseline CD4 count (per 100 cells/mm3) 1.05 (0.97–1.13)Time to suppression (months) 1.04 (0.99–1.09)ime to viral rebound among MSM who suppressed)P-value Adjusted hazard ratio(95 % confidence interval)P-value<0.001 1.00 <0.0010.50 (0.38–0.67)0.51 (0.38–0.69)<0.001 0.70 (0.62–0.80) <0.0010.008participants was 183 cells/mm3, whereas in 2011, thismeasure was 358 cells/mm3. Although an improvement,other studies have demonstrated that PHA who initiatecART with CD4 cell measures below 350 cells/mm3 areat higher risk of AIDS and death than individuals whobegin treatment at higher CD4 thresholds [35–37]. Re-current viral load testing among PHA who started cARTwith lower CD4 counts is crucial for informing changesin ARV regimens that are necessary for preventing treat-ment failure and adverse health outcomes.Our finding that higher baseline CD4 cell count wasa significant predictor of viral rebound was surprising[38, 39]. It is possible that cART adherent MSM withhigh baseline CD4 cell counts retained comparatively<0.001 1.00 <0.0012.52 (1.82–3.50)2.18 (1.09–4.36)<0.001 1.00 <0.0010.69 (0.53–0.91)0.43 (0.30–0.61)0.082 1.00 0.0571.48 (0.90–2.42)1.13 (0.86–1.48)1.70 (1.12–2.59)0.9990.4540.227 1.13 (1.05–1.22) 0.0010.118 1.04 (0.99–1.09) 0.144Tanner et al. BMC Infectious Diseases (2016) 16:590 Page 8 of 11better health throughout the study timeline, whichmay have influenced them to “take a break” from theirmedication [40, 41]. However, recent research set inthe Canadian context has found no association be-tween high CD4 counts (≥500 cells/mm3) and lowerrates of adherence [42]. Going forward, it is importantto examine this issue more closely. Recommendationsfor initiating cART immediately, regardless of CD4cell count, emerged after our period of study, first in2013 for select populations [10], and in 2015 for allPHA [37, 43]. As such, the proportion of PHA initiat-ing cART at higher CD4 counts will increase in the fu-ture, providing an opportunity to obtain a betterunderstanding of its predictive value regarding cARTadherence.This analysis discerned a few populations at risk ofpoorer virologic outcomes, including younger MSM andthose with a history of injection drug use. Adverse treat-ment response was particularly evident in this lattergroup, who had 0.71 times the likelihood of achievingsuppression, and over 2.5 times the chance of experien-cing rebound. Their reduced probability of achievingand sustaining undetectable viral loads hinders UNAIDSsuppression targets and has potential negative implica-tions for future health outcomes, and on going HIVtransmission. Younger MSM can face a wide array ofchallenges, including sexual identity issues, substanceabuse, precarious employment, and housing instability[44]. Understandably, these conditions may complicatebalancing a lifelong cART regimen and coming to termswith having a chronic and stigmatized disease. Healthcare providers with younger HIV-positive MSM patientsshould become more knowledgeable about local LGBT-focused hotlines, agencies, and media so that they canbetter connect them to these services, which may helpimprove HIV treatment self-efficacy and facilitate im-proved cART adherence [45]. Furthermore, HIV casemanagement services should accommodate more flexiblehours to promote continued engagement in care, asyounger HIV-positive MSM are more likely to missscheduled appointment times, and provide more flexiblescheduling as this been has previously demonstrated toimprove clinical care attendance and HIV treatmentresponse among this population [46]. For improvingtreatment responses among MSM who also use injectiondrugs, more intensive case management and psycho-social support services have a strong record of im-proving retention in care among more vulnerableHIV-positive populations [47, 48]. For example, in-corporating harm reduction services such as super-vised injection facilities into HIV care settings andincreasing the availability of methadone maintenancetherapy may also lead to more consistent viral loadsuppression among MSM-IDU [49, 50].Strengths and limitationsReaders should be cautious when reviewing our findingseven though our study was based on large group ofMSM and 12-year follow-up period. Most notably, ourstudy only included Canada’s three largest provinces,Ontario, Quebec and British Columbia, however, we didinclude most MSM as currently 85 % of PHAs inCanada live in these provinces [51]. The provincial dif-ferences in treatment response are likely explained bythe fact that British Columbia includes the entire sampleof CANOC-eligible individuals province-wide while datafrom Ontario and Québec included a selection of indi-viduals from specialized HIV clinics (the majority beingin urban centres). Men with missing or unknown MSMstatus (n = 2,073) were excluded from this analysis.Moreover, our results only pertain to MSM participantswho had at least two viral load measurements withinone year after initiating cART, as well as individuals withat least one year of follow-up. However, excluding thisgroup from our analyses did not heavily bias our results,because male participants with unknown MSM statusdid not differ from the MSM sample significantly withregard to baseline CD4 cell count, achieving suppres-sion, or experiencing rebound.ConclusionsOur results show that over 80 % of HIV-positive MSMwith at least one year of follow-up achieved and main-tained suppressed HIV viral levels. However, 12 % ofMSM who achieved viral suppression went on to experi-ence viral rebound within the study period. To betterrealize the UNAIDS 90 % suppression target, furtherstrategies are required to optimize cART outcomes inMSM in Canada, specifically targeting younger MSMand those with a history of IDU.AppendixThe CANOC Collaborative Research Centre includes:CANOC Principal Investigator: Robert Hogg (BritishColumbia Centre for Excellence in HIV/AIDS, SimonFraser University) Site Principal Investigators: Ann N.Burchell (Ontario HIV Treatment Network, University ofToronto, OHTN Cohort Study [OCS]), Curtis Cooper(University of Ottawa, OCS), Deborah Kelly (MemorialUniversity of Newfoundland), Marina Klein (MontrealChest Institute Immunodeficiency Service Cohort, McGillUniversity), Mona Loutfy (University of Toronto, MapleLeaf Medical Clinic, OCS), Nima Machouf (CliniqueMedicale l’Actuel, Université de Montréal), JulioMontaner (British Columbia Centre for Excellence inHIV/AIDS, University of British Columbia), JanetRaboud (University of Toronto, University Health Network,OCS), Chris Tsoukas (McGill University), Stephen Sanche(University of Saskatchewan), Alexander Wong (UniversityTanner et al. BMC Infectious Diseases (2016) 16:590 Page 9 of 11of Saskatchewan) Co-Principal Investigators: TonyAntoniou (St. Michael’s Hospital, University of Toronto,Institute for Clinical Evaluative Sciences), Ahmed Bayoumi(St. Michael’s Hospital, University of Toronto), Mark Hull(British Columbia Centre for Excellence in HIV/AIDS),Bohdan Nosyk (British Columbia Centre for Excellence inHIV/AIDS, Simon Fraser University) Co-Investigators:Angela Cescon (Northern Ontario School of Medicine),Michelle Cotterchio (Cancer Care Ontario, University ofToronto), Charlie Goldsmith (Simon Fraser University),Silvia Guillemi (British Columbia Centre for Excellence inHIV/AIDS, University of British Columbia), P. RichardHarrigan (British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia), Marianne Harris (St.Paul’s Hospital), Sean Hosein (CATIE), Sharon Johnston(Bruyère Research Institute, University of Ottawa), ClaireKendall (Bruyère Research Institute, University of Ottawa),Clare Liddy (Bruyère Research Institute, University ofOttawa), Viviane Lima (British Columbia Centre for Excel-lence in HIV/AIDS, University of British Columbia), DavidMarsh (Northern Ontario School of Medicine), DavidMoore (British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia), Alexis Palmer(British Columbia Centre for Excellence in HIV/AIDS,Simon Fraser University), Sophie Patterson (BritishColumbia Centre for Excellence in HIV/AIDS, SimonFraser University), Peter Phillips (British Columbia Centrefor Excellence in HIV/AIDS, University of BritishColumbia), Anita Rachlis (University of Toronto, OCS),Sean B. Rourke (University of Toronto, OCS), Hasina Samji(British Columbia Centre for Excellence in HIV/AIDS),Marek Smieja (McMaster University), Benoit Trottier(Clinique Medicale l’Actuel, Université de Montréal), MarkWainberg (McGill University, Lady Davis Institute forMedical Research), Sharon Walmsley (University HealthNetwork, University of Toronto) Collaborators: ChrisArchibald (Public Health Agency of Canada Centre forCommunicable Diseases and Infection Control), KenClement (Canadian Aboriginal AIDS Network), FredCrouzat (Maple Leaf Medical Clinic), MoniqueDoolittle-Romas (Canadian AIDS Society), Laurie Edmiston(Canadian Treatment Action Council), Sandra Gardner(OHTN, University of Toronto, OCS), Brian Huskins(Canadian Treatment Action Council), Jerry Lawless(University of Waterloo), Douglas Lee (University HealthNetwork, University of Toronto, ICES), Renee Masching(Canadian Aboriginal AIDS Network), Stephen Tattle(Canadian Working Group on HIV & Rehabilitation),Alireza Zahirieh (Sunnybrook Health Sciences Centre)Analysts and Staff: Claire Allen (Regina General Hospital),Stryker Calvez (SHARE), Guillaume Colley (BritishColumbia Centre for Excellence in HIV/AIDS), Jason Chia(British Columbia Centre for Excellence in HIV/AIDS),Daniel Corsi (The Ottawa Hospital ImmunodeficiencyClinic, Ottawa Hospital Research Institute), Louise Gilbert(Immune Deficiency Treatment Centre), Nada Gataric(British Columbia Centre for Excellence in HIV/AIDS), AliaLeslie (British Columbia Centre for Excellence in HIV/AIDS), Lucia Light (OHTN), David Mackie (The OttawaHospital), Costas Pexos (McGill University), SusanShurgold (British Columbia Centre for Excellence in HIV/AIDS), Leah Szadkowski (University Health Network),Chrissi Galanakis (Clinique Médicale L’Actuel), Ina Sandler(Maple Leaf Medical Clinic), Benita Yip (British ColumbiaCentre for Excellence in HIV/AIDS), Jaime Younger(University Health Network), and Julia Zhu (BritishColumbia Centre for Excellence in HIV/AIDS).AbbreviationsADI: AIDS-defining illness; AHR: Adjusted hazard ratio; AIC: Akaike InformationCriterion; AIDS: Acquired immune deficiency syndrome; ARV: Antiretroviral;BC: British Columbia; CANOC: Canadian Observational Cohort; cART: Combinationantiretroviral therapy; CI: Confidence interval; HCV: Hepatitis C; HIV: Humanimmunodeficiency virus; HR: Hazard ratio; IDU: Injection drug use; IRB: Institutionalreview board; LGBT: Lesbian, gay, bisexual and transgender; MSM: Men who havesex with men; MUHC: McGill University Health Centre; NNRTI: Nonnucleosidereverse transcriptase inhibitor; PHA: People living with HIV; PI: Protease inhibitor;REB: Research ethics board; RNA: Ribonucleic acid; UK: United Kingdom;UNAIDS: United Nations Programme on HIV/AIDSAcknowledgementsWe would like to thank all of the participants for allowing their informationto be a part of the CANOC collaboration.FundingCANOC is funded by the Canadian Institutes of Health Research (CIHR)through a Centres Grant (Centres for HIV/AIDS Population Health and HealthServices Research), two Operating Grants (HIV/AIDS Priority Announcement;Population and Public Health), and is also supported by the CIHR CanadianHIV Trials Network (CTN242). NJL is supported by a CANFAR/CTNPostdoctoral Fellowship Award. AC is supported through a CANOC CentreScholar Award. CC is supported through an Applied HIV Research Chair fromthe OHTN. MBK is supported by a Chercheur-Boursier Clinicien Senior CareerAward from the Fonds de recherche en santé du Québec (FRSQ). MRLreceives salary support from CIHR. JSGM is supported by an Avant-GardeAward from the National Institute on Drug Abuse, National Institutes ofHealth. SP is supported by a Study Abroad Studentship from the LeverhulmeTrust. JR is supported through an OHTN Chair in Biostatistics. The fundershad no role in study design, data collection and analysis, decision to publish,or preparation of the manuscript. The authors have no competing intereststo declare.Availability of data and materialsThere are data sharing agreements in place that prohibit the authors frommaking the data set publicly available. Readers may contact Dr. Robert Hoggfor further clarification.Authors’ contributionsThe author’s contributions are as follows: ZT, HS, ED, and JC conceived ofand designed the study. ED and JC performed all statistical analyses. Allauthors contributed to the interpretation of the data and reviewed themanuscript critically for important intellectual content. ZPT, NJL, and HShelped draft the manuscript. RSH advised on all aspects of the study. Allauthors read and approved the final manuscript.Competing interestsConflict of Interest: MBK reports grants from Merck and ViiV Healthcare andpersonal fees for consultancy from ViiV Healthcare, Bristol-Meyers Squibb,and Gilead Sciences. NM has been a speaker for Bristol-Meyers Squibb,Merck, and ViiV Healthcare. JSGM is supported by the British ColumbiaMinistry of Health and by the US National Institutes of Health (R01DA036307),Tanner et al. BMC Infectious Diseases (2016) 16:590 Page 10 of 11and he has received unrestricted funding, paid to his institution, from Abbvie,Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. JR is aco-investigator on two projects with in-kind contributions from Merck and GileadSciences, outside the submitted work. All other authors declare that they have nocompeting interest.Ethics approval and consent to participateThe human subjects activities of CANOC were approved by the Simon FraserUniversity Research Ethics Board, the University of British Columbia ResearchEthics Board and the following local institutional review boards of theparticipating cohorts: Providence Health Care Research Institute Office ofResearch Services, The Ottawa Hospital Research Ethics Board, UniversityHealth Network (UHN) Research Ethics Board, Véritas Institutional ReviewBoard (IRB), Biomedical C (BMC) Research Ethics Board of the McGillUniversity Heath Centre (MUHC), University of Toronto HIV Research EthicsBoard (HIV REB), and Women’s College Hospital Research Ethics Board. Localcohort studies have obtained written consent except for the following:HAART Observational Medical Evaluation and Research (IRB approves theretrospective use of anonymous administrative data without requiringconsent; an information sheet for participants is provided in lieu of aconsent form); Ottawa Hospital Cohort (IRB approves the anonymous use ofdata retrospectively abstracted from clinical care databases without requiringconsent); UHN (REB approves the anonymous use of data retrospectivelyabstracted from clinical care databases without requiring consent); MUHC(IRB approves the anonymous use of data retrospectively abstracted fromclinical care databases without requiring consent; patients sign a generalwaiver on opening a medical chart at the hospital but no specific studyrelated consent); Maple Leaf Medical Clinic (REB has approved theanonymous use of data retrospectively abstracted from clinical caredatabases without requiring consent); and Effective Anti-Retroviral Therapycohort (REB approves the anonymous use of data retrospectively abstractedfrom clinical care databases without requiring consent; patients sign ageneral waiver on opening a medical chart at the hospital but no specificstudy related consent).Author details1BC Centre for Excellence in HIV/AIDS, Vancouver, Canada. 2School of PublicHealth & Social Policy, University of Victoria, Victoria, Canada. 3Centre forAddiction Research British Columbia, University of Victoria, Victoria, Canada.4Faculty of Medicine, University of British Columbia, Vancouver, Canada.5Northern Ontario School of Medicine, Sudbury, Canada. 6Faculty of HealthSciences, Simon Fraser University, Vancouver, Canada. 7Dalla Lana School ofPublic Health, University of Toronto, Toronto, Canada. 8Toronto GeneralResearch Institute, University Health Network, Toronto, Canada. 9Faculty ofMedicine, University of Toronto, Toronto, Canada. 10Maple Leaf MedicalClinic, Toronto, Canada. 11Women’s College Research Institute, Women’sCollege Hospital, Toronto, Canada. 12The Ottawa Hospital Research Institute,University of Ottawa, Ottawa, Canada. 13Faculty of Medicine, McGillUniversity, Montreal, Canada. 14The Montreal Chest Institute, McGill UniversityHealth Centre, Montreal, Canada. 15Clinique Medicale l’Actuel, Montreal,Canada. 16Faculty of Health Sciences, Simon Fraser University, BLU 9512, 8888University Drive, Burnaby, BC V5A 1S6, Canada.Received: 22 June 2016 Accepted: 12 October 2016References1. 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A call to action for• Maximum visibility for your researchSubmit your manuscript atwww.biomedcentral.com/submit"@en ; edm:hasType "Article"@en ; dcterms:spatial "British Columbia"@en, "Ontario"@en, "Québec"@en ; edm:isShownAt "10.14288/1.0362085"@en ; dcterms:language "eng"@en ; ns0:peerReviewStatus "Reviewed"@en ; edm:provider "Vancouver : University of British Columbia Library"@en ; dcterms:publisher "BioMed Central"@en ; ns0:publisherDOI "10.1186/s12879-016-1926-z"@en ; dcterms:rights "Attribution 4.0 International (CC BY 4.0)"@en ; ns0:rightsURI "http://creativecommons.org/licenses/by/4.0/"@en ; ns0:scholarLevel "Faculty"@en ; dcterms:subject "HIV"@en, "MSM"@en, "Viral load"@en, "Suppression"@en, "Rebound"@en ; dcterms:title "Predictors of viral suppression and rebound among HIV-positive men who have sex with men in a large multi-site Canadian cohort"@en ; dcterms:type "Text"@en ; ns0:identifierURI "http://hdl.handle.net/2429/64080"@en .