Mark Gilbert

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).

HIV/AIDS in Vancouver, British Columbia: A Growing Epidemic

The prevalence of HIV in Vancouver, British Columbia was subject to two distinct periods of rapid increase. The first occurred in the 1980s due to high incidence among men who have sex with men (MSM), and the second occurred in the 1990s due to high incidence among injection drug users (IDU). The purpose of this study was to estimate and model the trends in HIV prevalence in Vancouver from 1980 to 2006. HIV prevalence data were entered into the UNAIDS/WHO Estimation and Projection Package (EPP) where prevalence trends were estimated by fitting an epidemiological model to the data. Epidemic curves were fit for IDU, MSM, street-based female sex trade workers (FSW), and the general population. Using EPP, these curves were then aggregated to produce a model of Vancouvers overall HIV prevalence. Of the 505 000 people over the age of 15 that reside in Vancouver, 6108 (ranging from 4979 to 7237) were living with HIV in the year 2006, giving an overall prevalence of 1.21 percent (ranging from 0.99 to 1.43 percent). The subgroups of IDU and MSM account for the greatest proportion of HIV infections. Our model estimates that the prevalence of HIV in Vancouver is greater than one percent, roughly 6 times higher than Canadas national prevalence. These results suggest that HIV infection is having a relatively large impact in Vancouver and that evidence-based prevention and harm reduction strategies should be expanded.

Azithromycin Prophylaxis during a Hospital Outbreak of Mycoplasma pneumoniae Pneumonia

Outbreaks of Mycoplasma pneumoniae (MP) in closed communities can have a high attack rate and can last several months. Azithromycin chemoprophylaxis has not been evaluated as a means of limiting transmission. This randomized, double-blinded placebo-controlled trial of azithromycin was conducted among asymptomatic hospital employees during an MP outbreak. Oropharyngeal swabs were obtained for detection of MP by polymerase chain reaction, and questionnaires were administered to assess clinical illness. Of the 147 employees who were enrolled, 73 received azithromycin and 74 received placebo. Carriage was similar within and between groups at weeks 1 and 6 (9.6% vs. 6.7% and 10.3% vs. 13.2%, respectively). Four episodes of clinically significant respiratory illness occurred in the azithromycin group versus 16 episodes in the placebo group (protective efficacy, 75%; 95% confidence interval, 28%-91%). Use of azithromycin prophylaxis in asymptomatic persons during an MP outbreak in a closed setting may be of value in reducing clinical illness.

Self-Collected versus Clinician-Collected Sampling for Chlamydia and Gonorrhea Screening: A Systemic Review and Meta-Analysis.

Background The increases in STI rates since the late 1990s in Canada have occurred despite widespread primary care and targeted public health programs and in the setting of universal health care. More innovative interventions are required that would eliminate barriers to STI testing such as internet-based or mail-in home and community service testing for patients that are hard to reach, who refuse to go for clinician-based testing, or who decline an examination. Jurisdictions such as New Zealand and some American states currently use self-collected sampling, but without the required evidence to determine whether self-collected specimens are as accurate as clinician-collected specimens in terms of chlamydia and gonorrhea diagnostic accuracy. The objective of the review is to compare self-collected vaginal, urine, pharyngeal and rectal samples to our reference standard - clinician-collected cervical, urethral, pharyngeal and rectal sampling techniques to identify a positive specimen using nucleic acid amplification test assays. Methods The hierarchical summary receiver operating characteristic and the fixed effect models were used to assess the accuracy of comparable specimens that were collected by patients compared to clinicians. Sensitivity and specificity estimates with 95% confidence intervals (CI) were reported as our main outcome measures. Findings We included 21 studies based on over 6100 paired samples. Fourteen included studies examined chlamydia only, 6 compared both gonorrhea and chlamydia separately in the same study, and one examined gonorrhea. The six chlamydia studies comparing self-collection by vaginal swab to a clinician-collected cervical swab had the highest sensitivity (92%, 95% CI 87-95) and specificity (98%, 95% CI 97-99), compared to other specimen-types (urine/urethra or urine/cervix). Six studies compared urine self-samples to urethra clinician-collected samples in males and produced a sensitivity of 88% (95% CI 83-93) and a specificity of 99% (95% CI 0.94-0.99). Taking into account that urine samples may be less sensitive than cervical samples, eight chlamydia studies that compared urine self-collected verses clinician-collected cervical samples had a sensitivity of 87% (95% CI 81-91) and high specificity of 99% (95% CI 0.98-1.00). For gonorrhea testing, self-collected urine samples compared to clinician-collected urethra samples in males produced a sensitivity of 92% (95% CI 83-97) and specificity of 99% (95% CI 0.98-1.00). Conclusion The sensitivity and specificity of vaginal self-collected swabs compared to swabs collected by clinicians supports the use of vaginal swab as the recommended specimen of choice in home-based screening for chlamydia and gonorrhea. Urine samples for gonorrhea collected by men had comparably high sensitivity and specificity, so could be recommended as they can be left at room temperature for several days, allowing for the possibility of mail-in home-based testing. In populations that may not go for testing at all, do not have the option of clinical testing, or who refuse a clinical examination, self-collected screening would be a good alternative. We recommend that guidelines on how to self-collect gonorrhea and chlamydia urine, vaginal, rectal and pharyngeal specimens be published.

Heteronormativity hurts everyone: experiences of young men and clinicians with sexually transmitted infection/HIV testing in British Columbia, Canada

Heteronormative assumptions can negatively influence the lives of young gay and bisexual men, and recent sociological analyses have identified the negative impacts of heteronormativity on heterosexual men (e.g. ‘fag discourse’ targeted at heterosexual adolescents). However, insights into how heteronormative discourses may be (re)produced in clinical settings and how they contribute to health outcomes for gay, bisexual and heterosexual men are poorly understood. This analysis draws on in-depth interviews with 45 men (15–25 years old) and 25 clinicians in British Columbia, Canada, to examine how heteronormative discourses affect sexually transmitted infection testing. The sexually transmitted infection/HIV testing experience emerged as a unique situation, whereby men’s (hetero)sexuality was explicitly ‘interrogated’. Risk assessments discursively linked sexual identity to risk in ways that reinforced gay men as the risky ‘other’ and heterosexual men as the (hetero)normal and, therefore, relatively low-risk patient. This, in turn, alleviated concern for sexually transmitted infection/HIV exposure in heterosexual men by virtue of their sexual identity (rather than their sexual practices), which muted discussions around their sexual health. The clinicians also positioned sexual identities and practices as important ‘clues’ for determining their patients’ social contexts and supports while concurrently informing particular tailored clinical communication strategies. These findings highlight how men’s experiences with sexually transmitted infection/HIV testing can (re)produce heteronormative assumptions and expectations or create opportunities for more equitable gendered relations and discourses.

Incidence, risk factors, and prevention of hepatitis C reinfection: a population-based cohort study

BACKGROUND People remain at risk of reinfection with hepatitis C virus (HCV), even after clearance of the primary infection. We identified factors associated with HCV reinfection risk in a large population-based cohort study in British Columbia, Canada, and examined the association of opioid substitution therapy and mental health counselling with reinfection. METHODS We obtained data from the British Columbia Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV at the British Columbia Centre for Disease Control Public Health Laboratory during 1990-2013 (when data were available). We defined cases of HCV reinfection as individuals with a positive HCV PCR test after either spontaneous clearance (two consecutive negative HCV PCR tests spaced ≥28 days apart without treatment) or a sustained virological response (SVR; two consecutive negative HCV PCR tests spaced ≥28 days apart 12 weeks after completing interferon-based treatment). We calculated incidence rates of HCV reinfection (per 100 person-years of follow-up) and corresponding 95% CIs assuming a Poisson distribution, and used a multivariable Cox proportional hazards model to examine reinfection risk factors (age, birth cohort, sex, year of HCV diagnosis, HCV clearance type, HIV co-infection, number of mental health counselling visits, levels of material and social deprivation, and alcohol and injection drug use), and the association of opioid substitution therapy and mental health counselling with HCV reinfection among people who inject drugs (PWID). FINDINGS 5915 individuals with HCV were included in this study after clearance (3690 after spontaneous clearance and 2225 after SVR). 452 (8%) patients developed reinfection; 402 (11%) after spontaneous clearance and 50 (2%) who had achieved SVR. Individuals were followed up for a median of 5·4 years (IQR 2·9-8·7), and the median time to reinfection was 3·0 years (1·5-5·4). The overall incidence rate of reinfection was 1·27 (95% CI 1·15-1·39) per 100 person-years of follow-up over a total of 35 672 person-years, with significantly higher rates in the spontaneous clearance group (1·59, 1·44-1·76) than in the SVR group (0·48, 0·36-0·63). With the adjusted Cox proportional hazards model, we noted higher reinfection risks in the spontaneous clearance group (adjusted hazard ratio [HR] 2·71, 95% CI 2·00-3·68), individuals co-infected with HIV (2·25, 1·78-2·85), and PWID (1·53, 1·21-1·92) than with other reinfection risk factors. Among the 1604 PWID with a current history of injection drug use, opioid substitution therapy was significantly associated with a lower risk of reinfection (adjusted HR 0·73, 95% CI 0·54-0·98), as was engagement with mental health counselling services (0·71, 0·54-0·92). INTERPRETATION The incidence of HCV reinfection was higher among HIV co-infected individuals, those who spontaneously cleared HCV infection, and PWID. HCV treatment complemented with opioid substitution therapy and mental health counselling could reduce HCV reinfection risk among PWID. These findings support policies of post-clearance follow-up of PWID, and provision of harm-reduction services to minimise HCV reinfection and transmission. FUNDING The British Columbia Centre for Disease Control and the Canadian Institutes of Health Research.

Cohort Profile: Seek and Treat for the Optimal Prevention of HIV/AIDS in British Columbia (STOP HIV/AIDS BC)

The Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) cohort is a census of all identified HIV-positive individuals in the province of British Columbia. It was formed through the linkage of nine provincial treatment, surveillance and administrative databases. This open cohort allows for bidirectional analyses from 1996 onward and is refreshed annually. Extensive data collection for cohort members includes demographic information, detailed clinical and laboratory data, complete prescription drug use including antiretroviral agents, and information on health service utilization encompassing inpatient and outpatient care, addictions treatment and palliative care. This cohort provides an unprecedented opportunity to evaluate, over an extended time period, patterns and determinants of key outcomes including engagement in the cascade of HIV care from diagnosis to treatment to viral suppression as well as monitoring trends in medical costs, health outcomes and other key healthcare delivery indicators at a population level with wide-ranging, high-quality data. The overall purpose of these activities is to enable the development and implementation of strategically targeted interventions to improve access to testing, care and treatment for all HIV-positive individuals living in British Columbia.

Cephalosporin and azithromycin susceptibility in Neisseria gonorrhoeae isolates by site of infection, British Columbia, 2006 to 2011.

Background Widespread resistance of Neisseria gonorrhoeae to penicillin, tetracycline, and fluoroquinolones has challenged effective treatment and control; recent international case reports of cefixime, ceftriaxone, and azithromycin resistance suggest that the remaining treatment options are now additionally threatened. To explore trends in antimicrobial susceptibility of N. gonorrhoeae, we reviewed provincial laboratory data from British Columbia, 2006 to 2011. Methods Susceptibility testing was performed for all N. gonorrhoeae isolates detected in-house or forwarded to the reference laboratory. Resistance or intermediate resistance (nonsusceptibility) was defined by standard breakpoints for penicillin, tetracycline, ciprofloxacin, and spectinomycin. Elevated minimum inhibitory concentrations (MICs) at serial dilutions of 0.064 &mgr;g/mL or greater were explored for cefixime/ceftriaxone and 0.5 &mgr;g/mL or greater for azithromycin. Nonsusceptibility/elevated MIC was compared by year, site of infection, sex, and age. Results A total of 1837 isolates representing 22% of all reported gonorrhea cases were analyzed. Nonsusceptibility to penicillin was established at baseline. Nonsusceptibility to tetracycline and ciprofloxacin increased over the study period, reaching 96% and 36%, respectively, in 2011. Sixteen isolates (1%) had a cefixime MIC of 0.25 &mgr;g/mL (none ≥0.5), none had a ceftriaxone MIC of 0.25 &mgr;g/mL or greater, and 15 (1%) had an azithromycin MIC of 2.0 &mgr;g/mL or greater. Elevated MIC of these agents showed an increasing trend over time. Nonsusceptibility and elevated MIC were consistently highest at the rectal and pharyngeal sites and higher in isolates from males, including when stratified to the pharyngeal site. Interpretation Increases in elevated MIC of cefixime/ceftriaxone/azithromycin were superimposed on a background of established resistance to penicillin, tetracycline, and ciprofloxacin and may signal impending gonococcal resistance to first-line treatments. Ongoing surveillance will inform timely shifts in treatment recommendations.

Application and Validation of Case-Finding Algorithms for Identifying Individuals with Human Immunodeficiency Virus from Administrative Data in British Columbia, Canada

Objective To define a population-level cohort of individuals infected with the human immunodeficiency virus (HIV) in the province of British Columbia from available registries and administrative datasets using a validated case-finding algorithm. Methods Individuals were identified for possible cohort inclusion from the BC Centre for Excellence in HIV/AIDS (CfE) drug treatment program (antiretroviral therapy) and laboratory testing datasets (plasma viral load (pVL) and CD4 diagnostic test results), the BC Centre for Disease Control (CDC) provincial HIV surveillance database (positive HIV tests), as well as databases held by the BC Ministry of Health (MoH); the Discharge Abstract Database (hospitalizations), the Medical Services Plan (physician billing) and PharmaNet databases (additional HIV-related medications). A validated case-finding algorithm was applied to distinguish true HIV cases from those likely to have been misclassified. The sensitivity of the algorithms was assessed as the proportion of confirmed cases (those with records in the CfE, CDC and MoH databases) positively identified by each algorithm. A priori hypotheses were generated and tested to verify excluded cases. Results A total of 25,673 individuals were identified as having at least one HIV-related health record. Among 9,454 unconfirmed cases, the selected case-finding algorithm identified 849 individuals believed to be HIV-positive. The sensitivity of this algorithm among confirmed cases was 88%. Those excluded from the cohort were more likely to be female (44.4% vs. 22.5%; p<0.01), had a lower mortality rate (2.18 per 100 person years (100PY) vs. 3.14/100PY; p<0.01), and had lower median rates of health service utilization (days of medications dispensed: 9745/100PY vs. 10266/100PY; p<0.01; days of inpatient care: 29/100PY vs. 98/100PY; p<0.01; physician billings: 602/100PY vs. 2,056/100PY; p<0.01). Conclusions The application of validated case-finding algorithms and subsequent hypothesis testing provided a strong framework for defining a population-level cohort of HIV infected people in BC using administrative databases.