Perry Kendall

Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study

BACKGROUND Results of cohort studies and mathematical models have suggested that increased coverage with highly active antiretroviral therapy (HAART) could reduce HIV transmission. We aimed to estimate the association between plasma HIV-1 viral load, HAART coverage, and number of new cases of HIV in the population of a Canadian province. METHODS We undertook a population-based study of HAART coverage and HIV transmission in British Columbia, Canada. Data for number of HIV tests done and new HIV diagnoses were obtained from the British Columbia Centre for Disease Control. Data for viral load, CD4 cell count, and HAART use were extracted from the British Columbia Centre for Excellence in HIV/AIDS population-based registries. We modelled trends of new HIV-positive tests and number of individuals on HAART using generalised additive models. Poisson log-linear regression models were used to estimate the association between new HIV diagnoses and viral load, year, and number of individuals on HAART. FINDINGS Between 1996 and 2009, the number of individuals actively receiving HAART increased from 837 to 5413 (547% increase; p=0.002), and the number of new HIV diagnoses fell from 702 to 338 per year (52% decrease; p=0.001). The overall correlation between number of individuals on HAART and number of individuals newly testing positive for HIV per year was -0.89 (p<0.0001). For every 100 additional individuals on HAART, the number of new HIV cases decreased by a factor of 0.97 (95% CI 0.96-0.98), and per 1 log(10) decrease in viral load, the number of new HIV cases decreased by a factor of 0.86 (0.75-0.98). INTERPRETATION We have shown a strong population-level association between increasing HAART coverage, decreased viral load, and decreased number of new HIV diagnoses per year. Our results support the proposed secondary benefit of HAART used within existing medical guidelines to reduce HIV transmission. FUNDING Ministry of Health Services and Ministry of Healthy Living and Sport, Province of British Columbia; US National Institute on Drug Abuse; US National Institutes of Health; Canadian Institutes of Health Research.

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.

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).

Effectiveness of neuraminidase inhibitors in preventing hospitalization during the H1N1 influenza pandemic in British Columbia, Canada

Objectives In British Columbia (BC), Canada, neuraminidase inhibitors (NIs) were publicly funded during the 2009 A(H1N1)pdm09 pandemic for treatment of high-risk patients and/or anyone with moderate-to-severe illness. We assessed antiviral effectiveness (AVE) against hospitalization in that context. Methods A population-based cohort study was conducted using linked administrative data. The cohort included all individuals living in BC during the study period (1 September to 31 December 2009) with a diagnostic code consistent with influenza or pandemic H1N1. The main study period pertained to the second-wave A(H1N1)pdm09 circulation (1 October to 31 December 2009), with sensitivity analyses around the more specific pandemic peak (18 October to 7 November). Exposure was defined by same-day NI prescription. The main outcome was all-cause hospitalization within 14 days of the outpatient influenza diagnosis. Cox proportional hazards models assessed AVE with 1 : 1 propensity-score matching and covariate adjustment. Results After matching, there were 304/58 061 NI-exposed and 345/58 061 unexposed patients hospitalized during the main study period. The very young [<6 months (35.0; 95% CI 16.7–73.4)], the old [65–79 years (13.7; 95% CI 10.1–18.6)] and the very old [≥80 years (38.7; 95% CI 26.6–56.5)] had the highest hospitalization rate per 1000 patients overall. Fully adjusted AVE against all-cause hospitalization during the main study period was 16% (95% CI 2%–28%), similar to the pandemic peak (15%; 95% CI −4%–30%). Conclusions The use of NIs was associated with modest protection against hospitalization during the 2009 pandemic, but appeared underutilized in affected age groups with the highest hospitalization risk.

Distribution of take-home opioid antagonist kits during a synthetic opioid epidemic in British Columbia, Canada: a modelling study

BACKGROUND Illicit use of high-potency synthetic opioids has become a global issue over the past decade. This misuse is particularly pronounced in British Columbia, Canada, where a rapid increase in availability of fentanyl and other synthetic opioids in the local illicit drug supply during 2016 led to a substantial increase in overdoses and deaths. In response, distribution of take-home naloxone (THN) overdose prevention kits was scaled up (6·4-fold increase) throughout the province. The aim of this study was to estimate the impact of the THN programme in terms of the number of deaths averted over the study period. METHODS We estimated the impact of THN kits on the ongoing epidemic among people who use illicit opioids in British Columbia and explored counterfactual scenarios for the provincial response. A Markov chain model was constructed explicitly including opioid-related deaths, fentanyl-related deaths, ambulance-attended overdoses, and uses of THN kits. The model was calibrated in a Bayesian framework incorporating population data between Jan 1, 2012, and Oct 31, 2016. FINDINGS 22 499 ambulance-attended overdoses and 2121 illicit drug-related deaths (677 [32%] deaths related to fentanyl) were recorded in the study period, mostly since January, 2016. In the same period, 19 074 THN kits were distributed. We estimate that 298 deaths (95% credible interval [CrI] 91-474) were averted by the THN programme. Of these deaths, 226 (95% CrI 125-340) were averted in 2016, following a rapid scale-up in distribution of kits. We infer a rapid increase in fentanyl adulterant at the beginning of 2016, with an estimated 2·3 times (95% CrI 2·0-2·9) increase from 2015 to 2016. Counterfactual modelling indicated that an earlier scale-up of the programme would have averted an additional 118 deaths (95% CrI 64-207). Our model also indicated that the increase in deaths could parsimoniously be explained through a change in the fentanyl-related overdose rate alone. INTERPRETATION The THN programme substantially reduced the number of overdose deaths during a period of rapid increase in the number of illicit drug overdoses due to fentanyl in British Columbia. However, earlier adoption and distribution of the THN intervention might have had an even greater impact on overdose deaths. Our findings show the value of a fast and effective response at the start of a synthetic opioid epidemic. We also believe that multiple interventions are needed to achieve an optimal impact. FUNDING Canadian Institutes of Health Research Partnerships for Health Systems Improvement programme (grant 318068) and Natural Science and Engineering Research Council of Canada (grant 04611).

Differences in experiences of barriers to STI testing between clients of the internet-based diagnostic testing service GetCheckedOnline.com and an STI clinic in Vancouver, Canada

Objectives Internet-based STI testing programmes may overcome barriers posed by in-clinic testing, though uptake could reflect social gradients. The role these services play in comparison to clinical testing services is unknown. We compared experiences of testing barriers between STI clinic clients to clients of GetCheckedOnline.com (GCO; where clients take a printed lab form to a lab). Methods Our 10-month cross-sectional study was conducted after GCO was promoted to STI clinic clients and men who have sex with men (MSM). Clinic and GCO clients completed an online survey assessing testing barriers and facilitators; responses were compared using bivariate analysis (level of significance P<0.01; significant results below). Results Compared with 321 clinic clients, the 73 GCO clients were more likely to be older (median 35 vs 30 years), MSM (45% vs 16%), be testing routinely (67% vs 39%), have delayed testing for any reason (76% vs 54%) and due to clinic distance (28% vs 9%), report delays due to wait times (50% vs 17%), embarrassment with testing (16% vs 6%), discomfort discussing sexual health where they usually go for testing (39% vs 22%), as well as discomfort discussing sexual history with (19% vs 5%) and fearing judgement from (30% vs 15%) any healthcare provider. GCO clients were less likely to have found clinic hours convenient (59% vs 77%) and clinic appointments easy to make (49% vs 66%), and more likely to report long wait times (50% vs 17%). We found no differences in technology skills/use. Conclusions In this urban setting, an internet-based testing service effectively engaged individuals experiencing testing barriers, with few social gradients in uptake. While some testing barriers could be addressed through increasing access to clinical services, others require social and structural changes, highlighting the importance of internet-based STI testing services to increasing test uptake.

At-a-glance - Impact of drug overdose-related deaths on life expectancy at birth in British Columbia

We quantified the contributions of leading causes of death and drug overdose to changes in life expectancy at birth over time and inequalities by sex and socioeconomic status in British Columbia. From 2014 to 2016, life expectancy at birth declined by 0.38 years and drug overdose deaths (mainly opioid-involved) contributed a loss of 0.12 years of the decrease. The analysis also demonstrated that the higher drug overdose mortality among males and among those in lower socioeconomic status communities contributed to a differential decrease in life expectancy at birth for males and for those in the latter category.

Secure care: more harm than good

KEY POINTS Many who overdose on drugs in British Columbia are youth under the age of 19 years,[1][1] and calls for “secure care” legislation have intensified. Secure care legislation would legitimize the detention and forced care of youth who are deemed to be at immediate risk of serious

Reviving a national prevention agenda is key to sustainability of health care in Canada

KEY POINTS Recent health funding agreements between the Canadian federal, provincial and territorial governments have centred on overall funding, with additional targeted funding for home care, mental health and addictions. However, if objectives related to fiscal sustainability, quality health care