Reka Gustafson

Expansion of HAART coverage is associated with sustained decreases in HIV/AIDS morbidity, mortality and HIV transmission: the "HIV Treatment as Prevention" experience in a Canadian setting.

Background There has been renewed call for the global expansion of highly active antiretroviral therapy (HAART) under the framework of HIV treatment as prevention (TasP). However, population-level sustainability of this strategy has not been characterized. Methods We used population-level longitudinal data from province-wide registries including plasma viral load, CD4 count, drug resistance, HAART use, HIV diagnoses, AIDS incidence, and HIV-related mortality. We fitted two Poisson regression models over the study period, to relate estimated HIV incidence and the number of individuals on HAART and the percentage of virologically suppressed individuals. Results HAART coverage, median pre-HAART CD4 count, and HAART adherence increased over time and were associated with increasing virological suppression and decreasing drug resistance. AIDS incidence decreased from 6.9 to 1.4 per 100,000 population (80% decrease, p = 0.0330) and HIV-related mortality decreased from 6.5 to 1.3 per 100,000 population (80% decrease, p = 0.0115). New HIV diagnoses declined from 702 to 238 cases (66% decrease; p = 0.0004) with a consequent estimated decline in HIV incident cases from 632 to 368 cases per year (42% decrease; p = 0.0003). Finally, our models suggested that for each increase of 100 individuals on HAART, the estimated HIV incidence decreased 1.2% and for every 1% increase in the number of individuals suppressed on HAART, the estimated HIV incidence also decreased by 1%. Conclusions Our results show that HAART expansion between 1996 and 2012 in BC was associated with a sustained and profound population-level decrease in morbidity, mortality and HIV transmission. Our findings support the long-term effectiveness and sustainability of HIV treatment as prevention within an adequately resourced environment with no financial barriers to diagnosis, medical care or antiretroviral drugs. The 2013 Consolidated World Health Organization Antiretroviral Therapy Guidelines offer a unique opportunity to further evaluate TasP in other settings, particularly within generalized epidemics, and resource-limited setting, as advocated by UNAIDS.

The cascade of HIV care in British Columbia, Canada, 1996-2011: a population-based retrospective cohort study

BACKGROUND The cascade of HIV care has become a focal point for implementation efforts to maximise the individual and public health benefits of antiretroviral therapy. We aimed to characterise longitudinal changes in engagement with the cascade of HIV care in British Columbia, Canada, from 1996 to 2011. METHODS We used estimates of provincial HIV prevalence from the Public Health Agency of Canada and linked provincial population-level data to define, longitudinally, the numbers of individuals in each of the eight stages of the cascade of HIV care (HIV infected, diagnosed, linked to HIV care, retained in HIV care, highly active antiretroviral therapy (HAART) indicated, on HAART, adherent to HAART, and virologically suppressed) in British Columbia from 1996 to 2011. We used sensitivity analyses to determine the sensitivity of cascade-stage counts to variations in their definitions. FINDINGS 13,140 people were classified as diagnosed with HIV/AIDS in British Columbia during the study period. We noted substantial improvements over time in the proportions of individuals at each stage of the cascade of care. Based on prevalence estimates, the proportion of unidentified HIV-positive individuals decreased from 49·0% (estimated range 36·2-57·5%) in 1996 to 29·0% (11·6-40·7%) in 2011, and the proportion of HIV-positive people with viral suppression reached 34·6% (29·0-43·1%) in 2011. INTERPRETATION Careful mapping of the cascade of care is crucial to understanding what further efforts are needed to maximise the beneficial effects of available interventions and so inform efforts to contain the spread of HIV/AIDS. FUNDING British Columbia Ministry of Health, US National Institute on Drug Abuse (National Institutes of Health).

Large Community Outbreak of Streptococcus pneumoniae Serotype 5 Invasive Infection in an Impoverished, Urban Population

BACKGROUND Streptococcus pneumoniae is a common cause of sporadic invasive infections, but outbreaks of invasive pneumococcal disease are infrequent. In August 2006, a sudden increase in the number of patients presenting with invasive pneumococcal disease was noted at St. Pauls Hospital (Vancouver, Canada). Most patients with severe disease resided in an area referred to as the Downtown Eastside, a neighborhood known for its high rates of poverty and illicit drug use. METHODS Prospective, laboratory-based surveillance for invasive pneumococcal disease was initiated, including on-site serotyping of S. pneumoniae isolates. A vaccination campaign using 23-valent polysaccharide pneumococcal vaccine was launched in the Downtown Eastside. Multiple logistic regression was used to examine the association of sociodemographic variables and medical risk factors with S. pneumoniae serotype status. RESULTS A single S. pneumoniae serotype (serotype 5) was responsible for 78% of invasive pneumococcal disease cases (137 of 175 cases) during the outbreak period of August 2006-July 2007. The outbreak strain, although fully susceptible to penicillin, caused significant morbidity and placed considerable strain on the acute care system within the Vancouver Coastal Health region. Crack cocaine use was found to be the main independent risk factor associated with invasive pneumococcal disease due to S. pneumoniae serotype 5 (odds ratio, 12.4; 95% confidence interval, 2.22-69.5). CONCLUSIONS A targeted vaccination campaign using polysaccharide pneumococcal vaccine appeared to help control this outbreak. In urban centers with high rates of illicit drug use, vaccination strategies for preventing invasive pneumococcal disease may need to be refined to include individuals who use crack cocaine.

Near real-time monitoring of HIV transmission hotspots from routine HIV genotyping: an implementation case study

Background Due to the rapid evolution of HIV, infections with similar genetic sequences are likely to be related by recent transmission events. Clusters of related infections can represent subpopulations with high rates of HIV transmission. Here we describe the implementation of an automated “near real-time” system using clustering analysis of routinely collected HIV resistance genotypes to monitor and characterize HIV transmission hotspots in British Columbia (BC). Methods A monitoring system was implemented on the BC Drug Treatment Database, which currently holds over 32000 anonymized HIV genotypes for nearly 9000 residents of BC living with HIV. On average, five to six new HIV genotypes are deposited in the database every day, which triggers an automated re-analysis of the entire database. Clusters of five or more individuals were extracted on the basis of short phylogenetic distances between their respective HIV sequences. Monthly reports on the growth and characteristics of clusters were generated by the system and distributed to public health officers. Findings In June 2014, the monitoring system detected the expansion of a cluster by 11 new cases over three months, including eight cases with transmitted drug resistance. This cluster generally comprised young men who have sex with men. The subsequent report precipitated an enhanced public health follow-up to ensure linkage to care and treatment initiation in the affected subpopulation. Of the nine cases associated with this follow-up, all had already been linked to care and five cases had started treatment. Subsequent to the follow-up, three additional cases started treatment and the majority of cases achieved suppressed viral loads. Over the following 12 months, 12 new cases were detected in this cluster with a marked reduction in the onward transmission of drug resistance. Interpretation Our findings demonstrate the first application of an automated phylogenetic system monitoring a clinical database to detect a recent HIV outbreak and support the ensuing public health response. By making secondary use of routinely collected HIV genotypes, this approach is cost-effective, attains near realtime monitoring of new cases, and can be implemented in all settings where HIV genotyping is the standard of care. Funding This work was supported by the BC Centre for Excellence in HIV/AIDS and by grants from the Canadian Institutes for Health Research (CIHR HOP-111406, HOP-107544), the Genome BC, Genome Canada and CIHR Partnership in Genomics and Personalized Health (Large-Scale Applied Research Project HIV142 contract to PRH, JSGM, and AFYP), and by the US National Institute on Drug Abuse (1-R01-DA036307-01, 5-R01-031055-02, R01-DA021525-06, and R01-DA011591).

Impact of Statistical Adjustment for Frequency of Venue Attendance in a Venue-based Survey of Men Who Have Sex With Men

Venue sampling is a common sampling method for populations of men who have sex with men (MSM); however, men who visit venues frequently are more likely to be recruited. While statistical adjustment methods are recommended, these have received scant attention in the literature. We developed a novel approach to adjust for frequency of venue attendance (FVA) and assess the impact of associated bias in the ManCount Study, a venue-based survey of MSM conducted in Vancouver, British Columbia, Canada, in 2008-2009 to measure the prevalence of human immunodeficiency virus and other infections and associated behaviors. Sampling weights were determined from an abbreviated list of questions on venue attendance and were used to adjust estimates of prevalence for health and behavioral indicators using a Bayesian, model-based approach. We found little effect of FVA adjustment on biological or sexual behavior indicators (primary outcomes); however, adjustment for FVA did result in differences in the prevalence of demographic indicators, testing behaviors, and a small number of additional variables. While these findings are reassuring and lend credence to unadjusted prevalence estimates from this venue-based survey, adjustment for FVA did shed important insights on MSM subpopulations that were not well represented in the sample.

Seek and treat to optimize HIV and AIDS prevention

Since 1996, highly active antiretroviral therapy (HAART) has transformed HIV into a chronic, manageable condition. HAART fully suppresses HIV replication, driving the HIV load in plasma to undetectable levels. This allows for immune reconstitution, long-term remission and dramatic reductions in

Whole-Genome Sequencing of Measles Virus Genotypes H1 and D8 During Outbreaks of Infection Following the 2010 Olympic Winter Games Reveals Viral Transmission Routes

We used whole-genome sequencing to investigate a dual-genotype outbreak of measles occurring after the XXI Olympic Winter Games in Vancouver, Canada. By sequencing 27 complete genomes from H1 and D8 genotype measles viruses isolated from outbreak cases, we estimated the virus mutation rate, determined that person-to-person transmission is typically associated with 0 mutations between isolates, and established that a single introduction of H1 virus led to the expansion of the outbreak beyond Vancouver. This is the largest measles genomics project to date, revealing novel aspects of measles virus genetics and providing new insights into transmission of this reemerging viral pathogen.

Avian Influenza A(H7N9) Virus Infection in 2 Travelers Returning from China to Canada, January 2015

In January 2015, British Columbia, Canada, reported avian influenza A(H7N9) virus infection in 2 travelers returning from China who sought outpatient care for typical influenza-like illness. There was no further spread, but serosurvey findings showed broad population susceptibility to H7N9 virus. Travel history and timely notification are critical to emerging pathogen detection and response.

Systematic community- and hospital-based surveillance for enterovirus-D68 in three Canadian provinces, August to December 2014

Respiratory specimens collected from outpatients with influenza-like illness in three Canadian provinces (British Columbia (BC), Alberta and Quebec) participating in a community-based sentinel surveillance network were prospectively screened for enterovirus-D68 (EV-D68) from 1 August to 31 December 2014 and compared to specimens collected from 1 October 2013 to 31 July 2014. Eighteen (1%) of 1,894 specimens were EV-D68-positive: 1/348 (0.3%) collected from October to December 2013 and 11/460 (2.4%) from October to December 2014, an eight-fold increase in detection rates (p=0.01), consistent with epidemic circulation in autumn 2014. The remaining EV-D68 detections were in September 2014 (6/37). Enhanced passive surveillance was also conducted on all inpatient and outpatient EV-D68 cases (n=211) detected at the BC provincial reference laboratory from 28 August to 31 December 2014. Incidence of hospitalisations was 3/100,000 overall and 21, 17, 4 and 1/100,000 among those<5, 5-9, 10-19 and ≥20-years-old with male-to-female ratios>1 among paediatric but not adult cases. Three cases in BC with comorbidity or co-infection died and five exhibited neurological features persisting >9 months. Active surveillance in outpatient and inpatient settings is needed from more areas and additional seasons to better understand EV-D68 epidemiology and potential at-risk groups for severe or unusual manifestations.

Relationship between disclosure of same-sex sexual activity to providers, HIV diagnosis and sexual health services for men who have sex with men in Vancouver, Canada.

OBJECTIVES: Men who have sex with men (MSM) report challenges to accessing appropriate health care. We sought to understand the relationship between disclosure of same-sex sexual activity to a health care practitioner (HCP), sexual behaviour and measures of sexual health care.METHODS: Participants recruited through community venues and events completed a questionnaire and provided a blood sample. This analysis includes only individuals with self-reported HIV negative or unknown serostatus. We compared participants who had disclosed having same-sex partners with those who had not using chi-square, Wilcoxon Rank Sum and Fisher’s exact tests and used logistic regression to examine those variables associated with receiving an HIV test.RESULTS: Participants who had disclosed were more likely to have a higher level of education (p<0.001) and higher income (p<0.001), and to define themselves as “gay” or “queer” (p<0.001). Those who had not disclosed were less likely to report having risky sex (p=0.023) and to have been tested for HIV in the previous two years (adjusted odds ratio 0.23, 95% confidence interval: 0.16–0.34). There was no difference in undiagnosed HIV infection (3.9% versus 2.6%, p=0.34). Individuals who had disclosed were also more likely to have been tested for gonorrhea and syphilis, and more likely to have ever been vaccinated against hepatitis A and hepatitis B (p<0.001 for all).CONCLUSIONS: While generally reporting lower risk behaviour, MSM who did not disclose same-sex sexual activity to their HCP did have undiagnosed HIV infections and were less likely to have been tested or vaccinated. Strategies to improve access to appropriate sexual health care for MSM are needed.RésuméOBJECTIFS: Les hommes ayant des relations sexuelles avec des hommes (HARSAH) disent avoir du mal à accéder à des soins de santé appropriés. Nous avons cherché à comprendre le lien entre la divulgation des relations homosexuelles à un professionnel de la santé (PS), le comportement sexuel et les indicateurs de soins de santé sexuelle.MÉTHODE: Les participants, recrutés dans des lieux et lors d’activités communautaires, ont rempli un questionnaire et fourni un échantillon de sang. Notre analyse n’a porté que sur les sujets ayant déclaré être séronégatifs pour le VIH ou ignorer leur état sérologique. À l’aide du test du khi-carré, du test de Wilcoxon et de la méthode exacte de Fisher, nous avons comparé les participants ayant divulgué le fait d’avoir des relations sexuelles avec d’autres hommes à ceux qui n’avaient pas divulgué leurs relations homosexuelles à un PS; au moyen d’une analyse de régression logistique, nous avons examiné les variables associées au fait d’avoir reçu un test de dépistage du VIH.RÉSULTATS: Les participants ayant divulgué leurs relations homosexuelles étaient plus susceptibles d’avoir un niveau de scolarité plus élevé (p<0,001) et un revenu plus élevé (p<0,001) et de se définir comme étant «gais» ou «queer» (p<0,001). Ceux qui n’avaient pas divulgué leurs pratiques homosexuelles à leur PS étaient moins susceptibles d’avoir eu des relations sexuelles à risque (p=0,023) et d’avoir été dépistés pour le VIH au cours des deux années antérieures (rapport de cotes ajusté de 0,23, intervalle de confiance de 95 %: 0,16–0,34). Il n’y avait pas de différence dans les infections à VIH non diagnostiquées (3,9 % c. 2,6 %, p=0,34). Les sujets ayant divulgué leurs relations homosexuelles étaient aussi plus susceptibles d’avoir été dépistés pour la gonorrhée et la syphilis et d’avoir été vaccinés contre l’hépatite A et l’hépatite B (p<0,001 pour tous).CONCLUSIONS: Bien qu’ils déclarent en général des comportements à moindre risque, les HARSAH qui n’avaient pas divulgué leurs relations homosexuelles à leur PS avaient parfois des infections à VIH non diagnostiquées, et ils étaient moins susceptibles d’avoir été dépistés ou vaccinés. Des stratégies pour améliorer l’accès aux soins de santé sexuelle adaptés aux HARSAH sont nécessaires.