The Efficacy of the Quadrivalent Human Papillomavirus Vaccine in Girls and Women Living With Human Immunodeficiency Virus.

BACKGROUND: Human papillomavirus (HPV) vaccination is safe and efficacious in women without human immunodeficiency virus (HIV). Although good immunogenicity has been observed in women living with HIV (WLWH), efficacy data in this population are needed. METHODS: We enrolled 420 females aged ≥9 years (range, 9-65) living with HIV. Participants were to receive 3 doses of qHPV vaccine (0/2/6 months). The main endpoint was vaccine failure (ie, incident persistent qHPV infection, cervical intraepithelial neoplasia of grade 2 or higher [CIN2+], or genital warts). We compared these rates to published rates in vaccinated and unvaccinated women without HIV as well as unvaccinated WLWH. RESULTS: Among 279 eligible women, median follow-up was 2 years. In the intention-to-treat population, the incidence rate (IR) of persistent qHPV (HPV6/11/16/18) was 2.3 per 100 person-years (/100PY) (95% confidence interval [CI], 1.1-4.1), and IR of genital warts was 2.3/100PY (95% CI, 1.2-4.1). In the per-protocol efficacy population, IR of persistent qHPV was 1.0/100PY (95% CI, 0.3-2.6) and of genital warts was 1.0/100PY (95% CI, 0.3-2.5). No cases of CIN2+ occurred. Reported rates of qHPV-related infection and disease within vaccinated women without HIV, unvaccinated women without HIV, and vaccinated WLWH: 0.1 (95% CI, 0.02-0.03), 1.5 (95% CI, 1.1-2.0), and 1.2 (95% CI, 0.2-3.4) /100PY, respectively. The rate of persistent qHPV among vaccinated WLWH was lower than among unvaccinated WLWH (2.3 vs 6.0/100PY). CONCLUSIONS: Vaccinated WLWH may be at higher risk for vaccine failure than vaccinated women without HIV. However, overall rates of vaccine failure were low, and rates of persistent qHPV were lower than in unvaccinated WLWH.

Using concept mapping to inform the development of a transitional reintegration intervention program for formerly incarcerated people with HIV.

BACKGROUND: Accessing HIV-related care is challenging for formerly incarcerated people with HIV. Interventions informed by the perspectives of these individuals could facilitate engagement with care and address competing priorities that may act as barriers to this process. METHODS: We used concept mapping to identify and prioritize the main obstacles to engaging with HIV-related care following prison release. In brainstorming sessions, formerly incarcerated people with HIV generated responses to a focused prompt regarding the main barriers to reengaging with care. These were consolidated in 35 statements. Next, participants sorted the consolidated list of responses into groups and rated each from lowest to highest in terms of its importance and feasibility of being addressed. We used cluster analysis to generate concept maps that were interpreted with participants. RESULTS: Overall, 39 participants participated in brainstorming sessions, among whom 18 returned for rating and sorting. Following analysis, a seven-cluster map was generated, with participants rating the 'Practical Considerations' (e.g. lack of transportation from prison) and 'Survival Needs' (e.g. securing housing and food) clusters as most important. Although ratings were generally similar between women and men, women assigned greater importance to barriers related to reconnecting with children. CONCLUSIONS: Using concept mapping, we worked with formerly incarcerated people with HIV to identify and prioritize key challenges related to accessing health and social services following prison release. Transitional intervention programs should include programs and processes that address meeting basic subsistence needs and overcoming logistical barriers related to community re-entry.

Social determinants of health and retention in HIV care in a clinical cohort in Ontario, Canada.

Continuous HIV care supports antiretroviral therapy initiation and adherence, and prolongs survival. We investigated the association of social determinants of health (SDH) and subsequent retention in HIV care in a clinical cohort in Ontario, Canada. The Ontario HIV Treatment Network Cohort Study is a multi-site cohort of patients at 10 HIV clinics. Data were collected from medical charts, interviews, and via record linkage with the provincial public health laboratory for viral load tests. For participants interviewed in 2009, we used three-category multinomial logistic regression to identify predictors of retention in 2010-2012, defined as (1) continuous care (≥2 viral loads ≥90 days in all years; reference category); (2) discontinuous care (only 1 viral load/year in ≥1 year); and (3) a gap in care (≥1 year in 2010-2012 with no viral load). In total, 1838 participants were included. In 2010-2012, 71.7% had continuous care, 20.9% had discontinuous care, and 7.5% had a gap in care. Discontinuous care in 2009 was predictive (p < .0001) of future retention. SDH associated with discontinuous care were Indigenous ethnicity, being born in Canada, being employed, reporting hazardous drinking, and non-injection drug use. Being a heterosexual male was associated with having a gap in care, and being single and younger were associated with discontinuous care and a gap in care. Various SDH were associated with retention. Care discontinuity was highly predictive of future gaps. Targeted strategic interventions that better engage those at risk of suboptimal retention merit exploration. ABBREVIATIONS: AOR: adjusted odds ratio; ART: antiretroviral therapy; AUDIT: Alcohol Use Disorders Identification Test; CES-D: Center for Epidemiologic Studies Depression Scale; CIs: confidence intervals; HIV: human immunodeficiency virus; IQR: interquartile range; MSM: men who have sex with men; NA-ACCORD: North American AIDS Cohort Collaboration on Research and Design; OCS: Ontario HIV Treatment Network Cohort Study; OHTN: Ontario HIV Treatment Network; OR: odds ratio; PHOL: Public Health Ontario Laboratories; REB: Research Ethics Board; SDH: social determinants of health; US: United States.

Hepatitis C virus seroconversion among HIV-positive men who have sex with men with no history of injection drug use: Results from a clinical HIV cohort.

BACKGROUND: Internationally, there is a growing recognition that hepatitis C virus (HCV) may be sexually transmitted among HIV-positive men who have sex with men (MSM). OBJECTIVE: To report the first Canadian estimate of HCV seroincidence in 2000 to 2010 and its risk factors among HIV-positive MSM with no known history of injection drug use. METHODS: Data from the Ontario HIV Treatment Network Cohort Study, an ongoing cohort of individuals in HIV care in Ontario, were analyzed. Data were obtained from medical charts, interviews and record linkage with the provincial public health laboratories. The analysis was restricted to 1534 MSM who did not report injection drug use and had undergone ≥2 HCV antibody tests, of which the first was negative (median 6.1 person-years [PY] of follow-up; sum 9987 PY). RESULTS: In 2000 to 2010, 51 HCV seroconversions were observed, an overall incidence of 5.1 per 1000 PY (95% CI 3.9 to 6.7). Annual incidence varied from 1.6 to 8.9 per 1000 PY, with no statistical evidence of a temporal trend. Risk for seroconversion was elevated among men who had ever had syphilis (adjusted HR 2.5 [95% CI 1.1 to 5.5) and men who had acute syphilis infection in the previous 18 months (adjusted HR 2.8 [95% CI 1.0 to 7.9]). Risk was lower for men who had initiated antiretroviral treatment (adjusted HR 0.49 [95% CI 0.25 to 0.95]). There were no statistically significant effects of age, ethnicity, region, CD4 cell count or HIV viral load. CONCLUSIONS: These findings suggest that periodic HCV rescreening may be appropriate in Ontario among HIV-positive MSM. Future research should seek evidence whether syphilis is simply a marker for high-risk sexual behaviour or networks, or whether it potentiates sexual HCV transmission among individuals with HIV.

HISTORIQUE: Sur la scène internationale, il apparaît de plus en plus clairement que le virus de l'hépatite C (VHC) peut être transmis sexuellement entre hommes positifs au VIH ayant des relations sexuelles avec des hommes (HARSAH). OBJECTIF: Rendre compte de la première estimation canadienne de la séro-incidence de VHC entre 2000 et 2010 et de ses facteurs de risque chez les HARSAH positifs au VIH sans antécédents connus de consommation de drogues injectables. MÉTHODOLOGIE: Les chercheurs ont analysé les données de l'Ontario HIV Treatment Network Cohort Study, une cohorte continue de personnes soignées pour le VIH en Ontario. Ils ont tiré les données de dossiers médicaux, d'entrevues et de liens entre les dossiers et les laboratoires provinciaux de santé publique. Ils ont restreint l'analyse à 1 534 HARSAH qui ne déclaraient pas consommer de drogues injectables et qui avaient subi au moins deux tests d'anticorps du VHC, dont le premier était négatif (suivi médian de 6,1 années-personne [AP]; somme de 9 987 AP). RÉSULTATS: De 2000 à 2010, les chercheurs ont observé 51 cas de séroconversion au VHC, pour une incidence globale de 5,1 cas sur 1 000 AP (95 % IC 3,9 à 6,7). L'incidence annuelle variait entre 1,6 et 8,9 cas sur 1 000 AP, sans preuve statistique de tendance temporelle. Le risque de séroconversion était élevé chez les hommes qui n'avaient jamais eu la syphilis (RR rajusté 2,5 [95 % IC 1,1 à 5,5) et chez les hommes qui avaient eu une infection aiguë par la syphilis dans les 18 mois précédents (RR rajusté 2,8 [95 % IC 1,0 à 7,9]). Le risque était plus faible chez les hommes qui avaient entrepris un traitement anti-rétroviral (RR rajusté 0,49 [95 % IC 0,25 à 0,95]). L'âge, l'ethnie, la région, la numération des cellules CD4 et la charge virale du VIH n'avaient pas d'effet statistiquement significatif. CONCLUSIONS: D'après ces observations, il serait judicieux de procéder au dépistage périodique du VHC chez les HARSAH positifs au VIH de l'Ontario. De prochaines recherches devraient viser à établir si la syphilis est un simple marqueur de comportements ou de réseaux sexuels à haut risque ou si elle potentialise la transmission sexuelle du VHC chez les personnes atteintes du VIH.

Demographic and clinical factors correlating with high levels of psychological distress in HIV-positive women living in Ontario, Canada.

The concept of psychological distress includes a range of emotional states with symptoms of depression and anxiety and has yet to be reported in HIV-positive women living in Ontario, Canada, who are known to live with contributing factors. This study aimed to determine the prevalence, severity, and correlates of psychological distress among women accessing HIV care participating in the Ontario HIV Treatment Network Cohort Study using the Kessler Psychological Distress Scale (K10). The K10 is a 10-item, five-level response scale. K10 values range from 10 to 50 with values less than or equal to 19 categorized as not clinically significant, scores between 20 and 24 as moderate levels, 25-29 as high, and 30-50 as very high psychological distress. Correlates of psychological distress were assessed using the Pearson's chi-square test and univariate and multivariate logistic regression analysis. Moderate, high, and very high levels of psychological distress were experienced by 16.9, 10.4, and 15.1% of the 337 women in our cohort, respectively, with 57.6% reporting none. Psychological distress levels greater than 19, correlated with being unemployed (vs. employed/student/retired; AOR = 0.33, 95% CI: 0.13-0.83), living in a household without their child/children (AOR = 2.45, 95% CI: 1.33-4.52), CD4 counts < 200 cells/mm(3) (AOR = 2.07, 95% CI: 0.89-4.80), and to a lesser degree an education of some college or less (vs. completed college or higher; AOR=1.71, 95% CI: 0.99-2.95). Age and ethnicity, a priori variables of interest, did not correlate with psychological distress. Findings suggest that socioeconomic factors which shape the demography of women living with HIV in Ontario, low CD4 counts, and losing the opportunity to care for their child/children has a significant relationship with psychological distress. Approaches to manage psychological distress should address and make considerations for the lived experiences of women since they can act as potential barriers to improving psychological well-being.

Dispersal of Mycobacterium tuberculosis via the Canadian fur trade.

Patterns of gene flow can have marked effects on the evolution of populations. To better understand the migration dynamics of Mycobacterium tuberculosis, we studied genetic data from European M. tuberculosis lineages currently circulating in Aboriginal and French Canadian communities. A single M. tuberculosis lineage, characterized by the DS6(Quebec) genomic deletion, is at highest frequency among Aboriginal populations in Ontario, Saskatchewan, and Alberta; this bacterial lineage is also dominant among tuberculosis (TB) cases in French Canadians resident in Quebec. Substantial contact between these human populations is limited to a specific historical era (1710-1870), during which individuals from these populations met to barter furs. Statistical analyses of extant M. tuberculosis minisatellite data are consistent with Quebec as a source population for M. tuberculosis gene flow into Aboriginal populations during the fur trade era. Historical and genetic analyses suggest that tiny M. tuberculosis populations persisted for ∼100 y among indigenous populations and subsequently expanded in the late 19th century after environmental changes favoring the pathogen. Our study suggests that spread of TB can occur by two asynchronous processes: (i) dispersal of M. tuberculosis by minimal numbers of human migrants, during which small pathogen populations are sustained by ongoing migration and slow disease dynamics, and (ii) expansion of the M. tuberculosis population facilitated by shifts in host ecology. If generalizable, these migration dynamics can help explain the low DNA sequence diversity observed among isolates of M. tuberculosis and the difficulties in global elimination of tuberculosis, as small, widely dispersed pathogen populations are difficult both to detect and to eradicate.

Vaginal microbiota associated with oncogenic HPV in a cohort of HPV-vaccinated women living with HIV.

BACKGROUND: Women living with HIV (WLWH) experience higher rates of human papillomavirus (HPV) infection and cervical cancer than women without HIV. Changes in the vaginal microbiome have been implicated in HPV-related disease processes such as persistence of high-risk HPV infection but this has not been well defined in a population living with HIV. METHODS: Four hundred and 20 girls and WLWH, age ≥9, across 14 clinical sites in Canada were enrolled to receive three doses of quadrivalent HPV vaccine for assessment of vaccine immunogenicity. Blood, cervical cytology, and cervico-vaginal swabs were collected. Cervico-vaginal samples were tested for HPV DNA and underwent microbiota sequencing. RESULTS: Principal component analysis (PCA) and hierarchical clustering generated community state types (CSTs). Relationships between taxa and CSTs with HPV infection were examined using mixed-effects logistic regressions, Poisson regressions, or generalized linear mixed-effects models, as appropriate. Three hundred and fifty-six cervico-vaginal microbiota samples from 172 women were sequenced. Human papillomavirus DNA was detected in 211 (59%) samples; 110 (31%) contained oncogenic HPV. Sixty-five samples (18%) were taken concurrently with incident oncogenic HPV infection and 56 (16%) were collected from women with concurrent persistent oncogenic HPV infection. CONCLUSIONS: No significant associations between taxa, CST, or microbial diversity and HPV-related outcomes were found. However, we observed weak associations between a dysbiotic microbiome and specific species, including Gardnerella, Porphyromonas, and Prevotella species, with incident HPV infection.

A randomized control trial of high-dose micronutrient-antioxidant supplementation in healthy persons with untreated HIV infection.

BACKGROUND: Although micronutrient and antioxidant supplementation are widely used by persons with human immunodeficiency virus (HIV), a therapeutic role beyond recommended daily allowances (RDA) remains unproven. An oral high-dose micronutrient and antioxidant supplement (Treatment) was compared to an RDA supplement (Control) for time to progressive immunodeficiency or initiation of antiretroviral therapy (ART) in people living with HIV (PLWH). METHODS: This study was a randomized, double-blind, placebo-controlled multicenter clinical trial. PLWH were recruited from Canadian HIV Trials Network sites, and followed quarterly for two years. Eligible participants were asymptomatic, antiretroviral treatment (ART)-naïve, HIV-seropositive adults with a CD4 T lymphocyte count (CD4 count) between 375-750 cells/µL. Participants were randomly allocated 1:1 to receive Treatment or Control supplements. The primary outcome was a composite of time-to-first of confirmed CD4 count below 350 cells/µL, initiation of ART, AIDS-defining illness or death. Primary analysis was by intention-to-treat. Secondary outcomes included CD4 count trajectory from baseline to ART initiation or two years. A Data and Safety Monitoring Board reviewed the study for safety, recruitment and protocol adherence every six months. RESULTS: Of 171 enrolled participants: 66 (38.6%) experienced a primary outcome: 27 reached a CD4 count below 350 cells/µL, and 57 started ART. There was no significant difference in time-to-first outcome between groups (Hazard Ratio = 1.05; 95%CI: 0.65, 1.70), or in time to any component outcome. Using intent-to-treat censoring, mean annualized rates of CD4 count decline were -42.703 cells/µL and -79.763 cells/µL for Treatment and Control groups, with no statistical difference in the mean change between groups (-37.06 cells/µL/52 weeks, 95%CI: (-93.59, 19.47); p = 0.1993). Accrual was stopped at 171 of the 212 intended participants after an interim analysis for futility, although participant follow-up was completed. CONCLUSIONS: In ART-naïve PLWH, high-dose antioxidant, micronutrient supplementation compared to RDA supplementation had no significant effect on disease progression or ART initiation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00798772.

Bacterial genetic signatures of human social phenomena among M. tuberculosis from an Aboriginal Canadian population.

Despite a widespread global distribution and highly variable disease phenotype, there is little DNA sequence diversity among isolates of Mycobacterium tuberculosis. In addition, many regional population genetic surveys have revealed a stereotypical structure in which a single clone, lineage, or clade makes up the majority of the population. It is often assumed that dominant clones are highly adapted, that is, the overall structure of M. tuberculosis populations is the result of positive selection. In order to test this assumption, we analyzed genetic data from extant populations of bacteria circulating in Aboriginal communities in Saskatchewan, Canada. Demographic parameters of the bacterial population were estimated from archival epidemiological data collected over approximately 130 years since the onset of epidemic tuberculosis in the host communities. Bacterial genetic data were tested against neutral theory expectations and the local evolutionary history of M. tuberculosis investigated by phylogenetic analysis. Our findings are not consistent with positive selection on the bacterial population. Instead, we uncovered founder effects persisting over decades and barriers to gene flow within the bacterial population. Simulation experiments suggested that a combination of these neutral influences could result in the stereotypical structure of M. tuberculosis populations. Some aspects of population structure were suggestive of background selection, and data were on the whole consistent with combined effects of population bottlenecks, subdivision, and background selection. Neutral phenomena, namely, bottlenecks and partitions within populations, are prominent influences on the evolution of M. tuberculosis and likely contribute to restricted genetic diversity observed within this species. Given these influences, a complex evolutionary model will be required to define the relative fitness of different M. tuberculosis lineages and, ultimately, to uncover the genetic basis for its success as a pathogen.

Ethnicity and gender differences in lipodystrophy of HIV-positive individuals taking antiretroviral therapy in Ontario, Canada.

PURPOSE: This study assessed ethnicity and gender differences in prevalence, type, and severity of antiretroviral-associated lipodystrophy in HIV-positive individuals in Ontario. METHODS: This was a cross-sectional analysis of the Ontario Cohort Study (OCS), a prospective study of HIV-positive patients in Ontario. Lipodystrophy was defined as at least 1 major or 2 minor self-reported changes of peripheral lipoatrophy and/or central lipohypertrophy. Prevalence, type, and severity were compared by ethnicity (Black, White, or Other) and gender. Univariate and multivariate logistic regression analyses identified predictors of lipodystrophy. RESULTS: Data were available for 778 participants (659 men, 119 women). There were 517 Whites, 121 Blacks, and 140 patients of Other ethnicities. In univariate analyses, Whites reported more peripheral lipoatrophy (P = .004) and abdominal lipohypertrophy (P = .04); these ethnic differences were observed in males (P = .05 and P = .03, respectively) but not females. Males reported more peripheral lipoatrophy (P = .01), whereas females had more central lipohypertrophy (P < .0001) and mixed fat redistribution (P < .0001). Multivariable regression analyses revealed Black women to be most vulnerable to lipodystrophy (P = .02), particularly lipohypertrophy (P < .0001). CONCLUSIONS: Ethnicity and gender are important factors influencing lipodystrophy. Combining lipoatrophy and lipohypertrophy into a single entity is not appropriate. Black women were most vulnerable to lipohypertrophy, which has important implications for antiretroviral therapy roll-out in Africa.

Tuberculosis: evidence review for newly arriving immigrants and refugees.

BACKGROUND: The foreign-born population bears a disproportionate health burden from tuberculosis, with a rate of active tuberculosis 20 times that of the non-Aboriginal Canadian-born population, and could therefore benefit from tuberculosis screening programs. We reviewed evidence to determine the burden of tuberculosis in immigrant populations, to assess the effectiveness of screening and treatment programs for latent tuberculosis infection, and to identify potential interventions to improve effectiveness. METHODS: We performed a systematic search for evidence of the burden of tuberculosis in immigrant populations and the benefits and harms, applicability, clinical considerations, and implementation issues of screening and treatment programs for latent tuberculosis infection in the general and immigrant populations. The quality of this evidence was assessed and ranked using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: Chemoprophylaxis with isoniazid is highly efficacious in decreasing the development of active tuberculosis in people with latent tuberculosis infection who adhere to treatment. Monitoring for hepatotoxicity is required at all ages, but close monitoring is required in those 50 years of age and older. Adherence to screening and treatment for latent tuberculosis infection is poor, but it can be increased if care is delivered in a culturally sensitive manner. INTERPRETATION: Immigrant populations have high rates of active tuberculosis that could be decreased by screening for and treating latent tuberculosis infection. Several patient, provider and infrastructure barriers, poor diagnostic tests, and the long treatment course, however, limit effectiveness of current programs. Novel approaches that educate and engage patients, their communities and primary care practitioners might improve the effectiveness of these programs.

Prevalent and persistent oncogenic HPV types in a cohort of women living with HIV prior to HPV vaccination.

OBJECTIVE: To describe prevalent and persistent oncogenic human papillomavirus (HPV) types detected in women living with HIV (WLWH) in Canada, including women with cervical dyskaryosis, and to determine predictors of type-specific HPV persistence. METHODS: Women and girls living with HIV, recruited from 14 sites of HIV care across Canada, were included in a sub-analysis of a prospective vaccine immunogenicity cohort study (two HPV DNA results, at least one cervical cytology result pre-vaccination). Demographic and clinical data were collected alongside cervical samples for cytology and HPV DNA typing between November 25, 2008, and May 19, 2015. RESULTS: Pre-vaccination, HPV16 and HPV52 were the most prevalent oncogenic HPV types. Of the 252 women and girls who met the eligibility criteria, 45% were infected with at least one oncogenic HPV type and one-third of participants had a persistent oncogenic infection. HPV16, 45, and 52 were the most frequently persistent types. Seventeen percent of women had persistent infections with oncogenic HPV types not within currently available vaccines (HPV35/39/51/56/59/68/82). Lower CD4 count significantly predicted HPV persistence (P=0.024). Cervical cytology results were normal for 82.9% of participants, atypical squamous cells of undetermined significance for 2.4%, low-grade squamous intraepithelial lesions for 11.5%, and high-grade squamous intraepithelial lesions for 2.8%. CONCLUSION: Unvaccinated WLWH were infected with a wide range of oncogenic HPV types. The findings highlighted the importance of optimal treatment of HIV and continued cervical cancer screening as key steps toward the global elimination of cervical cancer.

Impact of quadrivalent HPV vaccine dose spacing on immunologic response in women living with HIV.

HPV vaccination schedules have changed as evidence has supported reduced dosing and extended intervals. Women living with HIV (WLWH) represent an important population with no data on alternative dosing. Girls and WLWH received quadrivalent HPV (qHPV) vaccine in a pan-Canadian study of immunogenicity and efficacy. Serology was performed at months 0/2/7/12/18/24. Medical and sexual history was collected throughout. Linear regression was used to determine if spacing of doses was associated with peak antibody titer. Multivariable analyses demonstrated significant relationships between peak antibody titer and time to blood draw post last vaccine dose, naivety to the relevant HPV type, and HIV viral load for all qHPV types. There was a significant relationship between peak HPV16/18 antibody titer and age. Taking age, time to serology, CD4 cell count, CD4 nadir, HIV viral load, and HPV naivety into account, spacing of the three qHPV vaccine doses did not significantly impact peak antibody titers.

Brief Report: Persistence of Non-Vaccine Oncogenic HPV Genotypes in Quadrivalent HPV-Vaccinated Women Living With HIV.

BACKGROUND: Human papillomavirus (HPV) vaccines have promising safety and immunogenicity data in women living with HIV (WLWH). However, it is critical to understand the residual burden of oncogenic HPV within WLWH to inform postvaccination cervical screening needs. We assessed rates of persistent infection with nonquadrivalent HPV (qHPV) oncogenic types in a cohort of qHPV-vaccinated WLWH. SETTING: Multicentre, longitudinal cohort across Canada. METHODS: WLWH were scheduled to receive 3 doses of qHPV vaccine. Participants provided health data and HPV DNA samples. Persistent cases of HPV were defined as new HPV in samples from ≥2 consecutive visits or as HPV present in the last sample. HPV31/33/35/39/45/51/52/56/58/59/68/82 were considered to have oncogenic potential. Median follow-up time was 4 years after initial vaccine dose. RESULTS: A total of 284 participants were eligible for this analysis with 1205 person-years (PY) of follow-up (≥1 dose of vaccine, ≥1 HPV DNA result after vaccination). The highest incidence of persistent infection was with HPV51 (1.38/100 PY), followed by HPV52 (1.18/100 PY), and HPV39 (1.06/100 PY). The incidence of persistent infection with pooled HPV types added in the nonavalent vaccine (HPV31/33/45/52/58) was lower than the incidence of persistent oncogenic HPV types not contained within available vaccines (HPV35/39/51/56/59/68) (2.4/100 PY versus 3.6/100 PY, respectively). CONCLUSIONS: qHPV-vaccinated WLWH continue to face a burden of persistent oncogenic HPV infection. Although the nonavalent vaccine could alleviate some of this burden, 2 of the top 3 persistent oncogenic HPVs in this cohort are not contained within any available vaccine. This highlights the need for ongoing cervical screening in HPV-vaccinated WLWH.

Tuberculosis in Canada and the United States: a review of trends from 1953 to 2015.

OBJECTIVES: To explore tuberculosis (TB) incidence in Canada and the United States from 1953 to 2015. In the most recent decade, the US incidence was lower than that of Canada. Since both countries are high income and have low TB incidence with similar TB surveillance programs, we hypothesized that rates should be similar. METHODS: TB incidence data from 1953 to 2015 were retrieved for both countries. Joinpoint regression was performed to identify change points in the trend, and direct standardization of US rates using Canadian ethnic population distribution was calculated. Adjusted rate and average annual percent change (AAPC) were estimated. RESULTS: Canada rates/100,000 were higher from 1953 to 1974 and similar from 1975 to 1985. This coincided with a change in US case definition in 1975. US rates were higher from 1986 to 1996. HIV/TB coinfection in the USA was 10.2% compared to that of Canada, 1.6%. Rates were similar from 1997 to 2004. Canada rates were again higher from 2005 to 2015. The Canada average AAPC rate in 1975-2015 was lower, - 2.9%, compared to that of the USA, - 4.1%. Foreign-born and Indigenous population proportions were 20.2% and 4.2% for Canada and 12.9% and 1.7% for the USA. The US rate adjusted to the Canada ethnic composition was 4.8 compared to the Canadian rate of 4.7. CONCLUSION: Case definition change and HIV coinfection contributed to the 1980 US rate increase. TB rates decreased in both countries from 1997, but more rapidly in the USA. The Canada proportion of foreign-born and Indigenous populations was higher. When US rates were standardized by Canada ethnic distribution, the national rates were similar. Further exploration of factors contributing to differences between these countries is needed.

Delayed tuberculosis treatment in urban and suburban Ontario.

BACKGROUND: Delay in the treatment of patients with tuberculosis (TB) increases the risk of poor clinical outcomes--including death and transmission of disease--and may be reducible. OBJECTIVE: To estimate delays in TB treatment in a Canadian, multicultural population and to examine factors associated with longer time to treatment. METHODS: Adult cases of active TB from January 1998 to December 2001 from the Ontario Reportable Disease Information System were included. Time to treatment was defined as the number of days between symptom onset and treatment. RESULTS: Data from 1753 TB patients (76% of eligible patients) were analyzed. Median time to treatment was 62 days (interquartile range 31 to 114 days). Time periods longer than the median time to treatment were independently associated with middle-aged patients (OR 1.54, 95% CI 1.21 to 1.98), foreign-born patients who had lived in Canada for more than 10 years (OR 1.47, 95% CI 1.02 to 2.12), patients with nonpulmonary disease (OR 1.57, 95% CI 1.28 to 1.92) and patients managed within certain health districts. CONCLUSION: A time to TB treatment of two months or more is common in Ontario, and associated with several factors. Future studies are needed to build on these findings to decrease delay and improve individual and public health outcomes.

The Use of Multistate Models to Examine Associations of Stress and Adherence With Transitions Among HIV Care States Observed in a Clinical HIV Cohort.

BACKGROUND: The "cascade of care" is a framework for quantifying the trajectory of people with HIV along the continuum of HIV care. We extended this framework to recognize that individuals may transition back and forth between states of care and to identify factors associated with movement among states of care over time, with particular focus on stress, depression, and adherence. METHODS: The Ontario HIV Treatment Network Cohort Study is a multisite HIV clinical cohort. We analyzed data from participants who had initiated antiretroviral therapy, achieved virologic suppression, completed ≥1 study questionnaire including psychosocial data, and had ≥1 viral load (VL) result within 2 years of a questionnaire. Follow-up time from the first suppressed VL was divided into 6-month intervals and classified into 1 of 3 states for HIV care retention: (1) suppressed VL (VL <50 copies/mL), (2) unsuppressed VL (VL >50 copies/mL), and (3) unobserved. Multistate models were used to determine the association of transitioning between states and time-updated demographic and clinical characteristics. RESULTS: In total, 1842 participants were included. After multivariable adjustment, poor adherence [hazard ratio (HR) 1.88, 95% confidence interval (CI): 1.19 to 2.98) and stress (HR = 1.38; 95% CI: 1.04 to 1.83) were associated with transitions from suppressed to unsuppressed VL. Similarly, low adherence (HR = 1.52; 95% CI: 1.14 to 2.04) and stress (HR = 1.25; 95%: 1.03, 1.51) were associated with transitions from suppressed to unobserved states. CONCLUSIONS: Higher levels of stress and low adherence are associated with transitions to less favorable states of care. Interventions to manage stress and facilitate adherence may improve engagement in HIV care.

Potential role for interferon-γ release assays in tuberculosis screening in a remote Canadian community: a case series.

BACKGROUND: Current Canadian guidelines suggest that neonatal Bacille Calmette-Guérin (BCG) vaccination does not result in false-positive tuberculosis (TB) skin tests, despite a growing body of evidence that interferon-γ release assays may be a more specific alternative in identifying latent tuberculosis infections in vaccinated populations. We set out to evaluate the relationship between TB skin tests and interferon-γ release assays in patients who previously received neonatal BCG vaccine. METHODS: All children with a positive skin test at age 14 years in a remote community north of Sioux Lookout, Ontario, were considered for interferon-γ release assay testing. RESULTS: Of the 11 children who underwent routine screening at 14 years of age for latent TB infection, 7 had a positive TB skin test (≥ 10 mm). All 7 of these children had received the BCG vaccine as newborns and all had a negative TB skin test during their routine screening at 4 years of age. No potential exposure to active TB could be identified. Chest radiographs were normal, and none of the children had symptoms suggestive of active TB. The 7 children underwent interferon-γ release assay testing using QuantiFERON Gold. All 7 tests were negative. INTERPRETATION: With the addition of interferon-γ release assays to routine skin test screening, we provide evidence that neonatal BCG vaccination may contribute to a false-positive skin test in youth at 14 years of age. Consideration should be given to the possibility that neonatal BCG may contribute to false-positive TB skin tests.

Mortality over 12 years of follow-up in people admitted to provincial custody in Ontario: a retrospective cohort study.

BACKGROUND: We aimed to define rates and causes of death in custody and after release in people admitted to provincial custody in Ontario, and to compare these data with data for the general population. METHODS: We linked data on adults admitted to provincial custody in Ontario in 2000 with data on deaths between 2000 and 2012. We examined rates and causes of death by age, sex, custodial status and period after release, and compared them with data for the general population, using indirect adjustment for age. RESULTS: Between 2000 and 2012, 8.6% (95% confidence interval [CI] 8.3%-8.8%) of those incarcerated died in provincial custody or after release. The crude death rate was 7.1 (95% CI 6.9-7.3) per 1000 person-years. The standardized mortality ratio for those incarcerated in 2000 was 4.0 (95% CI 3.9-4.1) overall and 1.9 (95% CI 1.5-2.4) while in provincial custody. The most common causes of death were injury and poisoning (38.2% of all deaths), including overdose (13.6%) and suicide (8.2%), diseases of the circulatory system (15.8%) and neoplasms (14.5%). In the 2 weeks after release, the standardized mortality ratio was 5.7 overall and 56.0 for overdose. Life expectancy was 72.3 years for women and 73.4 for men who experienced incarceration in 2000. INTERPRETATION: Mortality was high for people who experienced incarceration, and life expectancy was 4.2 years less for men and 10.6 years less for women compared with the general population. Efforts should be made to reduce the gap in mortality between people who experience incarceration and those who do not. Time in custody could serve as an opportunity to intervene to decrease risk.

HIV viral suppression results in higher antibody responses in HIV-positive women vaccinated with the quadrivalent human papillomavirus vaccine.

OBJECTIVE: To evaluate the immunogenicity and safety of the quadrivalent HPV (qHPV) vaccine in HIV-positive women over 24months. DESIGN: Between November 2008 and December 2012, 372 women aged 15 and older were enrolled from 14 Canadian HIV outpatient clinics in an open label cohort study. The qHPV vaccine (0.5mL) was administered intramuscularly at months 0, 2 and 6. The primary study endpoint was seroconversion to any of the HPV types targeted by the qHPV vaccine. Antibody levels were measured at 0, 2, 7, 12, 18, and 24months. Adverse events were recorded throughout. RESULTS: Of 372 participants enrolled, 310 (83%) received at least one dose of the qHPV vaccine and 277 (74%) received all three doses. Ninety-five percent (293/308) were seronegative for at least one vaccine type at baseline. The median age was 38years (IQR 32-45, range 15-66), 36% were white, 44% black and 13% were of Indigenous origin. Seventy-two percent of participants had a suppressed HIV viral load (VL<40c/ml) at baseline, with a median CD4 count of 510cells/mm(3) (376-695). Month 7 HPV type-specific seroconversion rates were 99.0%, 98.7%, 98.1% and 93.6% for HPV types 6, 11, 16 and 18 respectively in the per-protocol population. Participants with suppressed HIV VL at first vaccine had a 1.74-3.05fold higher peak antibody response compared to those without (p from 0.006 to <0.0001). CONCLUSIONS: This study is the first to examine the qHPV vaccine in HIV-positive women out to 24months and the first to include HIV-positive women through to age 66. The qHPV vaccine was well tolerated, and highly immunogenic. As women with suppressed viral load had higher antibody responses, planning HPV vaccination to occur when persons are virologically suppressed would be optimal for maximizing immune response. Findings provide strong evidence that older HIV-positive women can still benefit from HPV vaccination. CLINICAL TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN33674451.