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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Implementation and Operational Research: Engagement in HIV Care Among Persons Enrolled in a Clinical HIV Cohort in Ontario, Canada, 2001-2011.

BACKGROUND: Ensuring that people living with HIV are accessing and staying in care is vital to achieving optimal health outcomes including antiretroviral therapy (ART) success. We sought to characterize engagement in HIV care among participants of a large clinical cohort in Ontario, Canada, from 2001 to 2011. METHODS: The Ontario HIV Treatment Network Cohort Study (OCS) is a multisite HIV clinical cohort, which conducts record linkage with the provincial public health laboratory for viral load tests. We estimated the annual proportion meeting criteria for being in care (≥1 viral load per year), in continuous care (≥2 viral load per year ≥90 days apart), on ART, and with suppressed viral load <200 copies per milliliter. Ratios of proportions according to socio-demographic and clinical characteristics were examined using multivariable generalized estimating equations with a log-link. RESULTS: A total of 5380 participants were followed over 44,680 person-years. From 2001 to 2011, we observed high and constant proportions of patients in HIV care (86.3%-88.8%) and in continuous care (76.4%-79.5%). There were statistically significant rises over time in the proportions on ART and with suppressed viral load; by 2011, a majority of patients were on ART (77.3%) and had viral suppression (76.2%). There was minimal variation in HIV engagement indicators by socio-demographic and HIV risk characteristics. CONCLUSIONS: In a setting with universal health care, we observed high proportions of HIV care engagement over time and an increased proportion of patients attaining successful virologic suppression, likely due to improvements in ART regimens and changing guidelines.

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.

Gender disparities in HIV risk behavior and access to health care in St. Petersburg, Russia.

Over 40,000 HIV-infected individuals live in St Petersburg, Russia. Population characteristics and barriers to care are largely undefined. 152 consecutive patients receiving HIV care at two sites completed a questionnaire in Spring 2011. Rates of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection, alcohol use, and rates of antiretroviral uptake were similar by gender. Males reported a higher history of injection drug use (80.3% vs. 48.7%; p<0.01) and tuberculosis infection (18.8% vs. 1.6%; p<0.01). Females were more likely to have had a child (63.3% vs. 31.5%; p<0.01) and be currently raising that child within their residence (49.3% vs. 15.3%; p<0.01). Unprotected sex (60.5% vs. 17.8%; p<0.01) and a history of sexually transmitted infection (37.7% vs. 20.3%; p=0.03) were more common in females. Females utilized social services more frequently (34.2% vs. 11.9%; p<0.01). There is a heavy burden of concurrent infectious disease, substance use and abuse, mental health illness, and need for social service support in this population. Important differences exist between genders in service uptake and utilization. Further evaluation of these differences may help inform the allocation of limited resources in this high HIV prevalence region of Russia.

Cohort profile: the Ontario HIV Treatment Network Cohort Study (OCS).

The Ontario HIV Treatment Network Cohort Study (OCS) is an observational, open dynamic cohort of people who are receiving medical care for human immunodeficiency virus (HIV) infection in Ontario, Canada. Established in the mid-1990s, the OCS has its roots in AIDS activists' demands for research that would improve the quality of life of people living with HIV while respecting their privacy. It is a collaborative and community-driven study, including a Governance Committee made up of people with HIV and other stakeholders that evaluates analysis project proposals for community relevance and ethics. From 1995 to 2010, a total of 5644 participants were enrolled and 27,720 person-years of observation were accumulated; follow-up will continue until at least 2015. In the initial years of study, the focus was on clinical data from medical chart reviews. It has since evolved into a comprehensive study that collects extensive de-identified information on clinical, laboratory and psychosocial and behavioural measures based on medical chart abstractions, interviews using a standardized questionnaire and linkage with external administrative health databases in Ontario. Interested collaborators are encouraged to submit analysis project proposals as instructed on the study website (www.ohtncohortstudy.ca).

IL-27-induced gene expression is downregulated in HIV-infected subjects.

OBJECTIVE: To characterize the effect of HIV infection on IL-27-induced gene expression. DESIGN: During HIV infection, cytokine expression and function become deregulated. IL-27 is an important modulator of inflammatory responses. Interestingly, IL-27 can inhibit HIV replication in T cells and monocytes, implicating IL-27 as a potential adjunct to anti-viral treatment. Our previous work demonstrated that circulating HIV may suppress IL-27 expression, therefore, this study, in continuation of our previous work, aimed to understand how HIV affects expression levels of the IL-27 receptor and downstream functions of IL-27. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from whole blood of HIV negative and HIV positive (viremic) individuals to assess IL-27-induced gene expression by flow cytometry and ELISA. PBMC were also processed for monocyte enrichment to assess IL-27 receptor expression by flow cytometry and real-time PCR. RESULTS: Expression of the IL-27 receptor subunit, gp130, was upregulated in response to IL-27 in HIV negative individuals, however, in HIV positive individuals, this IL-27 response was diminished. Furthermore, we observed downregulation of IL-27-induced IL-6, TNF-α, and IL-10 expression in HIV positive subjects. CONCLUSION: In HIV infection, IL-27-induced gene expression was impaired, indicating HIV-mediated dysregulation of IL-27 functions occurs during HIV infection. This study provides evidence for new viral pathogenic mechanisms contributing to the widespread impairment of immune responses observed in HIV pathogenesis.

Macrocytosis is a predictor of resting lactate concentrations in persons on dideoxynucleoside therapy for HIV infection.

OBJECTIVES: Mitochondrial toxicity is an important toxicity of antiretroviral therapy and may manifest as elevated blood lactate. Macrocytosis has been hypothesized to act as a marker of mitochondrial toxicity in persons with HIV infection. As part of a larger study on markers of mitochondrial toxicity we evaluated the relationship between resting lactate and erythrocyte mean corpuscular volume (MCV). METHODS: We studied the effect of micronutrient supplementation on lactate metabolism in three groups: those with HIV on and not on dideoxynucleoside-containing antiretroviral therapy and those without HIV. As part of the study we measured resting lactate and erythrocyte MCV after a 14-h fast. RESULTS: Erythrocyte MCV was significantly higher among the 11 participants on antiviral therapy (109.3 femtoliters (fl)) compared to five controls without HIV (89.3 fl) and four controls with HIV not on antiviral therapy (88.3 fl). In addition a strong predictive relationship was seen between MCV and resting lactate (R(2)=0.548, p<0.01). CONCLUSIONS: Macrocytosis may be a marker of treatment-related mitochondrial dysfunction in persons on treatment for HIV. Evaluating patients for early evidence of mitochondrial dysfunction in resource-constrained settings could be facilitated by this marker.