The IDC/CfE Journal Club is a critical review and discussion of recent scientific articles around HIV/AIDS-related topics. The Journal Club takes place twice a month on a Thursday 12-1PM in the BC-CfE Conference Room.
Click on the + sign to see a summary of the article.
- IDC Journal Club – Thursday, May 1, 2014
Andre Cahill presented the paper “Change in mental health after smoking cessation: systematic review and meta-analysis” by Taylor et al. in BMJ (2014). The authors examine the association between smoking and mental health, particularly the assumption held by some smokers that smoking helps to alleviate depression and anxiety. The authors conducted a systematic review and meta-analysis of observational data to compare mental health status among people who stop smoking and people who continue to smoke.
Eligibility criteria: studies of smokers that reported data on those who continued and those who quit smoking, studies that measured mental health before and after quitting, and only longitudinal studies (RCTs and cohort studies). 26 studies were included in the meta-analysis (11 cohort studies, 14 secondary analyses and 1 randomized trial).
Smoking cessation causes improvement in mental health and improving mental health causes cessation. Chronic tobacco smoking is associated with neuroadaptations in nicotinic pathways in the brain, which are in turn associated with depressed mood, agitation and anxiety shortly after smoking.
Critique and Discussion:
There may be a negative bias in the literature, i.e. less likely to publish negative results. There are limitations of self-reporting. Smoking cessation is an achievement that can have positive effect in itself. Article’s conclusion that the effects of smoking cessation matches those of antidepressants need to be clarified. The article challenges the notion that smoking helps with mood, anxiety, etc.
- IDC Journal Club – Thursday May 29, 2014
Dr. Mark Gilbert (BCCDC) presented his paper “Targeting screening and social marketing to increase detection of acute HIV infection in men who have sex with men in Vancouver, British Columbia” in AIDS (2013). The paper is based on a study that examines the impact of targeted nucleic acid amplification testing (NAAT) on identifying acute HIV infection (AHI). Pooled NAAT, introduced in BC in April 2009, can detect HIV infection within 7-15 days of infection. The study examined targeted implementation of pooled NAAT for MSM, who comprise the majority of new infections (58% in BC in 2011).
Pooled NAAT was implemented at a total of 6 clinics. Eligibility: Participants over 18 years of age who self-identify as men. Definition of AHI: detection of HIV RNA/DNA by NAAT or detection of p24 antigen. The study compared HIV diagnoses rates 36 months before and after the introduction of pooled NAAT in April 2009. Social marketing campaigns (posters, urinal ads, email blasts, etc.) were implemented by a community gay men’s organization to raise awareness about rapid testing, NAAT and AHI.
The rate of AHI diagnosis increased during the post-implementation period (1.03 to 1.84 per 1000 men tested, p=0.003). Of 217 new diagnoses after implementation of pooled NAAT, about 25% were AHIs.
Targeted pooled NAAT combined with social marketing is effective in detecting AHI detection among MSM compared to third generation enzyme immunoassay (EIA) testing.
- IDC Journal Club – Thursday June 12, 2014
Guillaume Colley presented his paper “The cascade of HIV care in British Columbia, Canada, 1996-2011: a population-based retrospective cohort study” in The Lancet (2014). The paper is based on a longitudinal population-based study of the numbers and proportions of individuals in each of the eight stages of the cascade of HIV care in BC from 1996-2011 (infected with HIV, diagnosed, linked to HIV care, retained in HIV care, need to be on HAART, on HAART, adherent to HAART and virologically suppressed).
The total number of HIV-positive individuals (diagnosed and undiagnosed) was drawn from Public Health Agency of Canada’s estimates. HIV-positive individuals in BC were categorized along the cascade using the data from: BCCDC for HIV testing (nominal); BC-CfE for plasma viral load (pVL), CD4 and antiretroviral (ARV) uptake; and Ministry of Health (MoH) for MSP billing and PharmaNet data for non-ARV drug dispensing. The number in each stage was calculated as a proportion of the number in the previous stage, not the total number of individuals, e.g. “virologically suppressed” are those people who are HAART adherent who have viral suppression and does not include those who have viral suppression without HAART adherence. “On HAART” was defined as at least 2 dispensation at least 3 months apart.
The proportion of individuals who are HIV-positive but undiagnosed fell from 49% to 29%. People who are on HAART but not adherent decreased from 24% to 13.4%. The greatest improvement: People who are adherent but not virologically suppressed decreased from 95.2% 21.6%. Meanwhile, people linked to care but not retained in care remained steady at around 20%.
The results of this analysis can help inform targeted healthcare interventions. More effort is needed in engaging HIV-positive individuals to remain in care and access HAART. Further HIV testing is also important but there is some uncertainty because the total number of HIV-positive individuals is an estimate. The study was limited by this estimation also by the number of HIV-positive individuals who are lost to care, who emigrate from the province, who access clinics billed by session (not captured by MoH) and who access treatment from clinical trials (not captured by BC-CfE). The BCCfE produces quarterly reports on the cascade of HIV care in BC, broken down further into health authorities and demographics. A cascade of HIV care analysis at the IDC between 2005-2013 showed that the number of linked patients increased threefold and virologically suppressed increased from 42% to 70%. This change is likely due to program changes (e.g. Peer Navigation, case management) and new treatment guidelines. The proportion of those who are on HAART but not HAART adherent remained constant at about 6%.
- IDC Journal Club – Thursday September 11, 2014
Tara Andrusiak (PGY2 from University of Ottawa) presented the paper “Tuberculosis screening and active tuberculosis among HIV-infected persons in a Canadian tertiary care centre” by Brassard et al. in Canadian Journal of Infectious Diseases & Medical Microbiology (2009). HIV infection increases the risk of reactivation of latent tuberculosis (TB). The study evaluates how latent TB is detected and treated to determine the effectiveness of screening in HIV-infected patients with diverse risk profiles.
A retrospective medical record database review (1988 to 2007) was conducted at a tertiary care HIV clinic. The proportion of patients receiving tuberculin skin tests (TST) and the rate of active TB at each stage of screening and prevention were estimated. Predictors of receiving a TST at baseline, testing positive by TST and developing active TB were evaluated.
2123 patients were observed. 22.4% were tested by TST within 90 days of clinic visit, as per guidelines. Independent predictors of receiving a TST at baseline were: having a first clinic visit during the HAART era, country of birth, time between HIV diagnosis and first visit and previous ARV exposure. Of the 17 patients who developed active TB during follow-up, 9 had no documented TSTs at baseline or during follow-up. 41% of all TB patients and 56% of TB patients who were not screened were born in Canada.
Administration of TSTs to newly diagnosed HIV patients was inconsistent and differential according to country of birth, among other factors, resulting in missed opportunities for TB prevention. For instance, at this clinic patients from TB endemic regions (i.e. Africa, Asia, Haiti and Latin America and the Caribbean) were more likely to be screened than Canadian-born patients.
- IDC Journal Club – Thursday October 30, 2014
Basia Hamata (Family Practice resident from Prince George) presented the paper “Is bone loss linked to chronic inflammation in antiretroviral-naïve HIV-infected adults? A 48-week matched cohort study” by Hileman et al. in AIDS (2014). The goal of the study was to evaluate changes in bone mineral density (BMD) without the confounding effects of ART. The authors hypothesized that HIV-positive ART-naïve adults would have a greater loss of BMD at hip and spine compared to HIV-uninfected adults.
A prospective matched cohort study over a 48-week period was conducted on HIV-positive, ART-naïve adults and HIV-negative control group matched by age, sex and race to determine the effect of HIV, systemic inflammation and vitamin D concentration on BMD over time. Inclusion criteria: HIV-positive individuals ≥ 18 years of age and ART-naïve and unlikely to require ART for at least 48 weeks (based on treatment guidelines at the time which recommended ART initiation at CD4 cell count ≤350 cells/μL). Exclusion criteria: Diabetes mellitus, active infectious or inflammatory condition, pregnancy or breastfeeding. HIV-positive participants were recruited from an immunology clinic in Cleveland, Ohio. 48-week period was chosen because the average time to ART initiation at the time the study was conducted was 2 years at the clinic. This period would also permit 2 DXA readings prior to ART initiation. For BMD measurement, Hologic scanner was used, performed at a single site. Technologists were blinded to the HIV status of participants. Blood was drawn after 12 hours fasting at entry and at week 48.
Data was collected between July 2010 and August 2012. 88 participants enrolled in the study (47 were HIV-positive). 11 did not complete the study. Median baseline and nadir CD4 counts were 625 (533-844) and 520 (452-618) cells/μL. HIV-1 RNA was 4638 (783-20,600) copies/mL and known duration of HIV infection was 4 (1.1-12.4) years. At baseline, the following were similar in the HIV-positive group and the HIV-negative control group: proportion of vitamin D insufficiency and deficiency, and BMD at total hip, femoral, neck, trochanter and spine. Baseline IL-6, STNFR-11, sVCAM-1 and sICAM-1 were higher in the HIV-positive group. Over the 48-week period, in the HIV-positive group, BMD at total hip and trochanter decreased. In the control group, BMD did not significantly change. However, changes in BMD did not reach statistical significance between groups. Site-specific comparison showed that HIV-infected group was 2.8 times more likely than control group to have bone loss at trochanter site. This risk persisted after adjustment for age, sex, race BMI, smoking and HCV. The effect of each inflammatory marker on the odds ratio for HIV status in a logistic regression model of bone loss showed that HIV status was not independently predictive of bone loss at trochanter site. 20.5% of HIV-positive participants progressed from normal bone to osteopenia or from osteopenia to osteoporosis, compared to 5.6% in the control group (p=0.089).
HIV-positive, ART-naïve adults had BMD loss at total hip and trochanter sites, although change in BMD did not reach statistical significance between groups. HIV-positive adults are more likely to have bone loss at trochanter site and this may be related to heightened inflammation.
Strengths of the article: Studying ART-naïve patient population allowed an opportunity to study the effect of HIV without the confounding effect of ART. This type of study may not be repeatable with the current guidelines. Weaknesses of the article: Small sample and short. A large difference in BMD changes between the groups was not observed. Implications for clinical practice: Preventive measures should be taken in all patients, e.g., weight-bearing exercises, decrease smoking and alcohol intake, adequate vitamin D and calcium.
- IDC Journal Club – Thursday June 25, 2015
Nathaniel Winata presented the paper “Use of Human Papillomavirus Vaccine in HIV-infected Men for the Prevention of Anal Dysplasia and Cancer” by Cachay & Mathews in AIDS Reviews (2014). The authors conducted a review to see if data suggests if the HPV vaccine should be given to HIV infected men who have sex with men (MSM) to decrease the rates anal cancer in this population. The authors discussed the efficacy of HPV vaccines to prevent anogenital warts/anal dysplasia and the key issues associated with HPV vaccination in HIV positive men.
The studies reviewed showed that the HIV positive MSM population have shown to have a three-fold increased risk of HPV infection in comparison to HIV negative MSM population.
The two vaccines that are currently out are the quadrivalent vaccine (Gardisil) and bivalent vaccine (Cervarix) which both protect against HPV 16 and 18 and the quadrivalent vaccine additionally protects HPV 6 and 11. There are no differences between bi and quad vaccines in safety and immunogenicity in HIV positive men. Clinical trials have shown the HPV vaccine as safe and induce robust response of HPV neutralizing antibodies among HIV positive patients. However, more research needs to be done on the long-term impact of HPV neutralizing antibody decay and other protective vaccine cell-mediated effects in the mucosal compartment
One clinical trial noted that the efficacy of HIV negative men who received the HPV vaccine prior to being exposed to HPV reduced external genital lesions by 90.4% while those who had been exposed to HPV prior to the HPV vaccine had a efficacy of 60.2% for any HPV-related lesion but an increased 65.5% for lesions related to HPV types 6, 11, 16 and 18.
Another study on HIV negative MSM 16-26 years of age were given the quad vaccine which prevented 50.3% of anal dysplasia types 6, 11, 16 and 18 in those who were exposed to the HPV infection before becoming vaccinated while 77.5% of anal dysplasia was prevented in those who had no prior exposure to HPV.
Canada’s National Advisory Committee of Immunization (NACI) recommends that boys and men between ages 9-26 be given quadrivalent HPV vaccine. The quadrivalent HPV vaccine for boys and men is not publicly funded in British Columbia. MSM do not benefit from herd immunity provided by vaccinating girls and women.
- IDC Journal Club – Thursday October 1, 2015
Nadia Fairbairn (PGY5 Internal Medicine) presented the paper “Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis” by Walley et al. in BMJ (2013). The authors evaluated the impact of a state supported education and nasal naloxone distribution (OEND) program on rates of opioid overdose related death and acute care utilization in the state of Massachusetts.
Interrupted time series analysis of opioid related overdose death and acute care utilization rates from 2002 to 2009 comparing community-year strata with high and low rates of OEND implementation to those with no implementation.
The OEND program trained 2912 bystanders who reported 327 opioid overdose rescues. Both community-year strata with 1-100 enrollments per 100,000 population and community-year strata with greater than 100 enrollments per 100,000 population had significantly reduced adjusted rate ratios compared with communities with no implementation. Differences in rates of acute care hospital utilization were not significant.
The study concluded that communities where OEND was implemented had a reduced death rate from opioid overdose death rates. Evidence shows that by training potential bystanders to prevent, recognize, and respond to opioid overdoses, OEND is an effective intervention.
Clearly the use of naloxone in the appropriate context has significant survival benefits. Health Canada has not yet approved nasal naloxone. Intramuscular (IM) naloxone kits are approved and are available for free at the IDC. No prescription is needed from a physician. IDC nurses are trained to supply the naloxone kits and to provide education on drug overdose. Furthermore, these interactions are good opportunities for talking with patients about harm reduction and education on drug use. Training for using IM naloxone is provided weekly in the St. Paul’s Hospital dining room.
- IDC Journal Club – Thursday November 26, 2015
Ryan Herriot (R3 Enhanced Skills HIV, UBC Family Practice) discussed the report “Culture, Context and the Mental Health and Psychosocial Wellbeing of Syrians” by the United Nations High Commissioner for Refugees. The paper discusses the mental health concerns of Syrian refugees. There is a wide range of emotional, cognitive, physical, and behavioural and social challenges Syrians refugees face.
Canada’s refugee system
There are two main categories of resettled refugees:
- Government-Assisted Refugees (GARs): The federal government funds a network of settlement agencies to provide assistance to GARs and provides income support for up to 12 months.
- Privately Sponsored Refugees (PSRs): Are supported by private sponsors that include income support and practical assistance for the first year.
The incoming group of refugees from Syria will be a mixture of both groups. A key difference between Canada and Germany is that we have existing refugee resettlement services so we are comparatively well-positioned to successfully integrate and care for Syrian refugees. The HIV-positive refugees who arrive in the lower mainland will receive their primary care from Bridge Clinic for the first year. The greatest challenge will be transitioning patients to other clinics following the first year.
Anticipated Syrian health concerns
Syrian refugees are expected to have a low burden of infectious diseases as Syria had a robust public vaccination program. However, vaccinations coverage in Syria has dropped from 90% in 2010 to 52% in 2014. The majority of refugees are expected to be experiencing symptoms of distress. Although many refugees have been through major traumas, evidence indicates that how well they are supported in their new lives after resettling is by far the bigger driver of mental health. The refugees are likely to describe their mental health symptoms as a combination of physical and psychological symptoms. Two co-existing cultural phenomena that contribute to this apparent somatization are:
- An understanding of illness that takes into account both physical psychological contributions
- A reticence to acknowledge the existence of or seek help for mental health problems
Therefore, conventional mental health interventions, while important, are not necessarily the biggest piece of the puzzle. Culturally creative approaches may be necessary in instances where mental health interventions are required.
Primary Care Guidelines for refugees
Below is a link to an evidence-based preventative care checklist for new immigrants and refugees from the Central Middle East: http://www.ccirhken.ca/ccirh/checklist_website/en/central_middle_east.html .
- IDC Journal Club – Thursday February 18, 2016
Bria Sharkey (PR3 Enhanced Skills HIV, UB) presented the paper “On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 infection” by Molina et al. in The New England Journal of Medicine (2015). Antiretroviral preexposure prophylaxis has shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among, studies, probably due to challenges of adherence to a daily regimen. The goal of the study was to assess the efficacy and safety of sexual activity- dependent preexposure prophylaxis with TDF-FTC among high risk men who have sex with men in France and Canada.
A double-blind, randomized trial of antiretroviral therapy for pre-exposure HIV-1 prophylaxis among men who have unprotected anal sex with men. Participants were randomly assigned to take a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or placebo before and after sexual activity. All participants received risk-reduction counselling and condoms and were regularly tested for HIV-1 and HIV- 2 and other sexually transmitted infections.
A total of 16 HIV-1 infections occurred during follow-up, 2 in the TDF-FTC group and 14 in the placebo group, a relative reduction in the TDF-FTC group of 86%. Participants took a median of 15 pills of TDF-FTC or placebo per month. The rates of serious adverse events were similar in the two study groups. In the TDF-FTC group, as compared with the placebo group, there were higher rates of gastrointestinal adverse events and renal adverse events.
The study concluded that the use of TDF-FTC before and after sexual activity provided protection against HIV-1 infection in men who have sex with men. However, the treatment was associated with increased rates of gastrointestinal and renal adverse events.
- IDC Journal Club – Thursday April 14, 2016
Miguel Pedromingo (Internal Medicine Resident) presented on the paper “Opioid Abuse in Chronic Pain- Misconceptions and Mitigation Strategies” by Volkow et al., The New England Journal of Medicine (2016). The review focuses on pharmacologic properties of opioids that underlie both their therapeutic effects and their abuse-producing effects and on the ways in which these properties should inform us in correction common clinical misconceptions that interfere with the proper prescription and monitoring of opioids in the management of chronic pain.
The authors expand on the misunderstanding among physicians regarding the important differences between physical dependence and addiction.
The rewarding effects of opioids play a major role in the risks of opioid diversion, overdose, and addiction. There are common strategies that can help mitigate all risks, including limiting the prescribed opioid to the lowest effective dose for the shortest effective duration without compromising effective analgesia
Preventing drug diversion
-Screening tools to identify patients with substance-use disorder
-Use data from the Prescription Drug Monitoring Program
Reducing Risk of overdose
-Overdose risk assessment
-Urine drug screening before prescription of opioids
-Opioid treatment agreement
-Caution prescribing high doses or long-acting opioids
Minimizing the risk of addiction
-Primary care setting
-Assessment of addiction risks
-Referral for specialty addiction treatment when indicated
-Comprehensive, continuing care and monitoring
The authors recommend three practice and policy changes that can reduce abuse-related risks and improve the treatment of chronic pain. The three recommendations are increasing use of science-supported prescribing and management practices, increasing medical school training on pain and addiction and increasing research on pain.
- IDC Journal Club – Thursday May 26, 2016
Tara Andrusiak (R3 Enhanced Skills HIV) presented on the paper “Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals” by Marcus et al., Journal of Acquired Immune Deficiency Syndromes (2016). The authors evaluated the effect of abacavir on CVD in HIV-infected individuals initiating ART, using inverse-probability weighting estimation.
The authors studied 8154 subjects without prevalent CVD who had initiated their first combination ART regimen after abacavir was introduced.
8154 patients were observed. 178 individuals had great or equal to 1 CVD event, 3.4% in the abacavir group and 2.1% in the group without abacavir. The individuals on abacavir had more renal dysfunctions at antiretroviral therapy initiation.
The study concluded that abacavir was associated with an over 2-fold increased risk of CVD, which was not explained by renal dysfunction or other risk factors. Thus, physicians must weigh the benefits of abacavir vs. the risks of CVD when prescribing it to patients.
- IDC Journal Club – Thursday June 23, 2016
Serena Chalmers presented on the paper “Hydromorphone Compared with Diacetylmorphine for Long-term Opioid Dependence-A Randomized Trail” Dr. Eugenia Oviedo-Joekes and colleagues published at JAMA Psychiatry 2016 May 1;73(5):447-55. The study objective was to test if injectable hydromorphone hydrochloride is non-inferior to injectable diacetylmorphine in reducing illicit heroin use for chronic injection opioid users after 6 months of intervention.
This was a double-blind randomized clinical trial on 202 long term street opioid injectors in Vancouver, BC. Participants either received injectable diacetylmorphine or hydromorphone (up to 3 times daily) for 6 months under supervision. The outcomes measured were inclusive of self-reported days of street heroin use, days of any street-acquired opioids in the prior 30 days, and the proportion of urinalyses positive for street heroin markers.
Study concluded a non-inferiority of injectable hydromorphone relative to diacetylmorphine for long-term opioid dependence. In areas where diacetylmorphine is not available or for patients in whom it is contraindicated, hydromorphone could be offered as an alternative. The proportion of urinalyses positive for street heroin markers was also estimated with margin of 10% of the observed rate in the diacetylmorphine group.
Critique and Discussion:
A limitation of this study is the fact that two of the study outcomes were based on self-report of street heroin users, although urine sample increased the reliability by reducing the reporting bias. The study suggest that hydromorphone is as effective as diacetylmorphine for individuals with severe opioid use disorder and can be used as an alternative licensed drug for maintenance treatment of opioid users.
- IDC Journal Club – Thursday June 23, 2016
Nancy Chow presented a paper on the acceptability and feasibility of pharmacist-provided rapid testing for human immunodeficiency virus (HIV) infection in community pharmacies. Apart from rapid HIV testing, consultation and linkage to confirmatory HIV testing services was also implemented in two sites in Michigan. The title of the paper was “Pharmacist-provided rapid HIV testing in two community pharmacies” published by Journal of the American Pharmacists Association (2015; 55:81-88).
Marketing techniques were employed to select study participants for free rapid (median time of 30 minutes) HIV testing. Understudy outcomes were inclusive of number of HIV tests performed, time required for HIV testing services, description of participants who received an HIV test, and pharmacist and participant perception of the HIV testing experience.
Participants had a median age of 23 (range, 18–61) years and were diverse by gender (59.4% women) and race (46.4% black; 39.1% white). This was the first HIV test for 42% of participants, many of whom reported high risk behaviors in the prior 6 months. Participants and pharmacists reported favorable perceptions of the HIV testing experience. The acceptability and feasibility of pharmacist-provided rapid HIV testing in two community pharmacies with
distinct characteristics were demonstrated in this study.
Critique and Discussion:
This was a small study based on a non-randomized population, hence non-representative of all populations who may choose to receive pharmacy-based HIV testing. Moreover, may have overestimated the time required to conduct HIV testing due to inability to differentiate between time spent on study versus usual testing activity. Free HIV testing in the study may not truly reflect the feasibility of a paid- pharmacy.
- IDC Journal Club – Thursday Sep 15, 2016
Sanjeev Bains presented evidence based drug information on “Opioids in Chronic Non-Cancer Pain”, aimed to inform the audience on the benefits and harms of opioid prescribing. Significant evidence gaps exist in this area of treatment including the unknown benefits and harms with using opioid therapy in chronic non-cancer pain patients. Poor efficacy, intolerable short-term side effects and opioid misuse disorder are common ongoing concerns with every patient. For these reasons, an opioid trial of 2-6 weeks is recommended, along with frequent and close monitoring eg. every 3 months.
- CfE Journal Club – Thursday September 29, 2016
Ignacio Rozada presented a research project aimed at estimating the impact of treatment churn on HIV transmission risk. Individuals in the acute and late-stage phases of HIV have higher transmission risk (26 and 7 times respectively), whereas individuals on ART that are virologically suppressed are estimated to have only a 4% relative transmission risk when compared to a chronic untreated individual. We estimated a measure of lifetime risk by combining these risk estimates with life expectancy based on several scenarios that depended on treatment adherence.
They estimated the lifetime transmission risk, defined as the number of chronic-equivalent days from HIV infection to death, among individuals in both the natural history and on-ART scenarios. The natural history risk estimates were determined from known viral load and life expectancy curves. The on-ART scenario combined estimates on life expectancy, treatment churn and associated changes in viral load to estimate transmission risk.
It was estimated that individuals in the natural history scenario have a lifetime risk of 12.7 chronic-equivalent years, on a life expectancy of 11 years. In the on-ART scenario, we estimated that individuals with high adherence have 7.0 risk years on 47.3 years of life expectancy, individuals at median adherence had 8.9 risk years on 33.8 years of life expectancy, and individuals with low adherence had 11.4 risk years on 17.6 years of life expectancy.
Critique and Discussion:
Despite significant increases in life expectancy in individuals on ART, the overall lifetime transmission risk is lower than the natural history scenario. In fact, individuals with the longest life expectancies are estimated to have the lowest lifetime transmission risk.
- CfE Journal Club – Thursday November 24, 2016
Pilar Vizcarra presented on the paper “Atrial Fibrillation and Atrial Flutter in Human Immunodeficiency Virus-Infected Persons” by Hsu et al. in the Journal of the American College of Cardiology (2013). The authors investigated the associations of traditional risk factors and longitudinal measures of human immunodeficiency virus (HIV) severity with the risk of incident atrial fibrillation (AF) in a contemporary cohort of people living with HIV (PLHIV).
They examined the independent associations of demographic characteristic, time-updated comorbidities, and time-updated clinical measurments including CD4+ cell count and plasma viral load (pVL) with the outcome of incident AF using proportional hazards regression for multivariable analysis.
In their cohort of PLHIV, they found an incidence rate of AF of 3.6/1,000 person-years. Lower CD4+ cell count and higher pVL, assessed by multiple time-updated measures, were independently associated with development of AF. Older age and the presence of traditional risk factors increased the risk of AF.
Critique and Discussion:
A limitation of this study is the fact that they did not include a control group, making difficult to compare frequency rates with general population. However, it is the first study to assess AF incidence rates in PLHIV, suggesting that HIV infection severity may be linked with the development of AF.
- IDC Journal Club – Thursday Dec 8, 2016
Joanna Mereu presented the paper “HIV Associated Neurocognitive Disorders in the Modern Antiviral Treatment Era: Prevalence, Characteristics, Biomarkers, and Effects of Treatment” by Chan P. and Brew B. in Current HIV/AIDS reports (2014).
The introduction of cART has changed not only the HIV related morbidity and mortality but also the neurocognitive impairment associated with HIV from HAND to milder forms (Asymptomatic Neurocognitive Impairment and Mild Neurocognitive Disorder). Various plasma and CSF biomarkers are currently considered as predictors of cognitive impairment and several radiological tools are discussed as providing radiological evidence of disease.The variable CNS penetration by ARVs is also discussed as well as the progression of neurocognitive impairment despite an undetectable plasma viral load, which suggests continuing CNS viral replication.
Despite significant advances in cART, neurocognitive impairment remains prevalent in HIV patients. These impairments, although milder, continue to progress despite good adherence to treatment and an undectable viral load. This deserves further work in identifying better biomarkers of disease and a better use of current radiological tools. CNS penetrating ARV regimes will also need to be further refined.
- CfE Journal Club – Thursday Jan 19, 2017
Kiffer Card presented the paper “Exploring the role of sex-seeking apps and websites in the social and sexual lives of gay, bisexual and other men who have sex with men: a cross-sectional study” by Card et al. in Sexual Health (2016). The authors examine the association between online sex seeking and a number of other explanatory factors focusing on demographics, social behaviour, and prevention-related sexual behaviour.
Gay, bisexual, and other men who have sex with men were recruited into the Momentum Health Study using respondent-driven sampling, a form of referral-chain based sampling. Cross-sectional data were used to identify the covariates of online sex-seeking in the past six months.
Contrary to what is commonly believed, univariable results show that men who seek sex online were not less likely to participate in the gay community. Multivariable results showed that online sex seekers were more likely to be younger, college educated, have more Facebook friends, spend more social time with other gay men, and were less likely to identify emotionally with the gay community. Further, they had displayed high sensation-seeking behaviour, were more likely to engage in serodiscordant/unknown condomless anal sex, use strategic positioning, ask their partner’s HIV-status prior to sex, and have ever been tested for HIV.
Critique and Discussion:
Although online sex-seekers engage in greater CAS, they are not necessarily at greater risk for HIV considering they are more likely to engage in greater risk-reducing behaviour. However, acknowledging that there may be greater risk in online settings due to imperfect application of these prevention strategies, promoting pro-social altruistic interventions and interventions with messaging that is acceptable to men with high sexual sensation seeking might be effective strategies to negate the risks occurring in the environments. Considering that online sex-seekers were no less likely to connect in person, these prevention campaigns should use both online and offline methods to reach online-sex seekers.
- IDC Journal Club – Thursday March 2, 2017
Nicholas Baldwin presented an overview of a study titled “The efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in antiretroviral regimens for HIV-1 therapy”, a meta-analysis published by Wang et al. in the journal Medicine in 2016. In this study, the authors reviewed the literature comparing a novel form of the nucleotide reverse transcriptase inhibitor tenofovir alafenamide, also known by the abbreviated form ‘TAF’, to the existing agent tenofovir disoproxil fumarate (TDF). TAF has been proposed to be an equally efficacious form of tenofovir with less renal and bone toxicity, which is a well-documented phenomenon observed with TDF containing regimens.
The authors performed a literature review, retrieving articles published up until March 2016, that included randomized controlled trials with HIV-1 infected patients over the age of 18, comparing treatment with TAF vs. TDF containing regimens. 6 RCTs involving 5888 patients were selected for the meta-analysis which included treatment-naïve patients and treatment-experienced patients who were switched from TDF to TAF containing regimens. The outcomes observed were treatment efficacy, as defined by a viral load
At week 48, viral suppression rates were similar between the TAF and TDF groups (90.2% vs. 89.5% respectively) for treatment-naïve patients, and superior for treatment-experienced patients who switched from TDF to TAF containing regimens (96.4% vs. 93.1%). Both agents were well tolerated with low rates of treatment failure and resistance. The group receiving TAF had significantly smaller reductions in eGFR and less proteinuria. The treatment naïve group receiving TAF showed a lesser reduction in bone mineral density (BMD), and the treatment experienced patients who switched from TDF to TAF demonstrated an increase in BMD at both the hip and spine. The TAF group showed increases in levels of total cholesterol, HDL, and LDL, with no change in the total cholesterol/HDL ratio.
The authors conclude that TAF has a similar efficacy and tolerability to TDF in treatment experienced and naïve patients, with improved safety in terms of renal and bone toxicity. A limitation to this study is the relative homogeneity of third agents used in the RCTs selected. 86.5% of patients in the TAF group were receiving regimens containing elvitegravir/cobicistat as a third agent. There is still somewhat limited data on patients taking TAF with protease inhibitors, NNRTs, or other integrase inhibitors other than elvitegravir. TAF is now available through the CFE formulary for selected patients.
- CfE Journal Club – Thursday March 30, 2017
Heather Armstrong presented the analysis “HIV testing among gay, bisexual, and other men who have sex with men in the Momentum Health Study”. These analyses were presented at the Canadian Association of HIV Research Conference and at the Congress of the World Association for Sexual Health in April and May 2017, respectively.
The Momentum Health Study is a 4-year longitudinal, biobehavioural cohort study looking at the sexual health of gay, bisexual, and other men who have sex with men (GBM) in Greater Vancouver, with respect to HIV treatment and prevention. The study uses Respondent Driven Sampling to obtain a representative sample of GBM living in and around Vancouver. The aims of the present analysis were to: 1) identify the proportion of GBM who had tested for HIV in the past 2 years, tested earlier than the past 2 years, and who had never tested; 2) describe men’s reasons for testing or not testing; 3) identify factors associated with not having a test in the past 2 years; and 4) examine uptake and factors associated with HIV rapid testing.
Using baseline data of 535 participants (HIV negative or diagnosed as HIV positive in the past 2 years), 80% had tested for HIV within the past 2 years, 11% had tested but not in the past 2 years, and 9% had never tested for HIV. The most common reason for testing was that it was part of a regular routine; other reasons included testing after a risk event or after starting a new relationship. Among men who had never tested, the most common reasons for not testing was considering oneself to be at low risk and wanting to test but just not having done it yet. Men who had not tested in the past 2 years were more likely to identify as bisexual, as belonging to the “other” ethnicity category (vs. White), live outside of the city of Vancouver, and be 45 years of age or older. They were also less likely to practice viral load sorting, to ask their partners’ HIV status more than half the time, and to have tested for other STIs in the past 6 months. Latino GBM (vs. White) and those who were not “out” were more likely to have had a test in the past 2 years. Rapid HIV testing was more common among GBM who lived downtown and who tested at sexual health clinics. Rapid testing also effectively engaged some hard-to-reach GBM including those who were not “out” and those who usually receive medical care at hospital emergency rooms.
Further efforts should be made to engage GBM in HIV testing, particularly for bisexual and older GBM, and those living outside of Vancouver. Rapid testing effectively engaged some hard-to-reach GBM and increasing access to rapid testing (for example, if the test was available from family doctors) may improve diagnosis and treatment outcomes.
- CfE Journal Club – Thursday April 13, 2017
Brittany Barker presented a paper “Medical cannabis and mental health: a guided systematic review,” by Walsh et al. in Clinical Psychology Review (2017). Given the rise in the use of cannabis for therapeutic purposes (CTP), the authors’ objective in the review was to provide health practitioners with evidence regarding the use and risks of cannabis.
In addition to a review of studies of CTP and mental health outcomes, a parallel review was conducted of non-medical use cannabis (NMC) and mental health outcomes. However, given that the relationship between NMC and mental health outcomes has been studied extensively, the authors elected to only include meta-analyses. In total 31 studies for CTP and 29 meta-analyses for NMC were included.
The authors found evidence to suggest that CTP has the potential to treat anxiety disorders, PTSD and substance use disorders (i.e., CTP as a substitute for problematic illicit drug use). However, CTP may influence cognitive assessment, particularly with regard to memory, although tolerance, mode of administration and dosage may attenuate these effects and there is little evidence to suggest long-term deficits after a period of abstinence. Research reviewed regarding the use of CTP among individuals with mood disorders was inconsistent and extrapolating from NMC reviews, the authors concluded that CTP may be problematic for individuals with psychotic disorders. The majority of studies reviewed observed that CTP was effective in the alleviation of depressive symptoms; however, NMC reviews demonstrated that there was a modest increase in the risk for development and severity of depression. Lastly, no evidence was found to support that CTP increases the risk of harm to self or others.
Critique and discussion:
The authors note that the CTP studies reviewed were mostly cross-sectional, of lower methodological quality and that further clinical and longitudinal research is needed. Additionally, many attendees to the discussion felt the authors overstated the positive findings between CTP and mental health outcomes.
- IDC Journal Club – Thursday May 11, 2017
Ashley Goodman, Shelda Kastor, Elmer Azak, and Tracey Morrison presented the paper ‘“They treated me like crap and I know it was because I was Native”: The healthcare experiences of Aboriginal peoples living in Vancouver’s inner city’ by Goodman et al. in Social Science & Medicine (2017). A short documentary film based on the publication was also presented.
In response to the healthcare inequalities that burden Aboriginal peoples, this research aimed to explore the healthcare experiences of Aboriginal peoples who use(d) illicit drugs and/or illicit alcohol living in Vancouver’s inner city. In partnership with the BC Centre for Excellence in HIV/AIDS, Board Members of the Western Aboriginal Harm Reduction Society served as community researchers and led the study design, data collection and analysis. Peer-facilitated talking circles were used to explore community members’ experiences accessing healthcare services and patient-provider encounters.
Participants’ stories demonstrated how healthcare inequalities among Aboriginal peoples are perpetuated by cultural and institutional racism. Stigmatizing racial stereotypes were perceived to influence individual attitudes and clinical practice. Symptoms and health concerns were described as trivialized by healthcare practitioners, and were perceived to result from stigma attached to Aboriginal ancestry, illicit substance use, and living in the inner city. This dismissal often resulted in disengagement from care or delay in care.
The findings suggest healthcare providers must apply their knowledge of the social determinants of health in order to understand the structural forces that influence racial disparities in healthcare and personal biases in clinical practice. Adequate clinical protocols for pain management within the context of illicit substance use are urgently needed. The valuation of Aboriginal peoples and cultures within healthcare is paramount to addressing the health gap between Aboriginal and non-Aboriginal Canadians.
For more information about the Western Aboriginal Harm Reduction Society: http://wahrs.ca/
Recommended resource for cultural competency and safety in healthcare settings: http://www.sanyas.ca/training
- CfE Journal Club – Thursday June 8, 2017
Peter Cheung presented on the paper “Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial” by Sax et al. published in the journal of Lancet HIV. 2017 Apr;4(4):e154-e160. The author report findings for a phase II clinical trial comparing bictegravir with dolutegravir.
All recent treatment guidelines recommend integrase strand transfer inhibitors (INSTIs) as components of initial HIV therapy. Bictegravir, a novel, once-daily, unboosted INSTI, showed potent activity in a 10 day monotherapy study and has a high in-vitro resistance barrier. On the basis of these results, we did a phase 2 trial comparing bictegravir with dolutegravir.
In this randomised, double-blind, phase 2 trial, we recruited previously untreated adults (aged ≥18 years) with HIV-1 infections from 22 outpatient centres in the USA. Eligible patients had HIV-1 RNA concentrations of at least 1000 copies per mL, CD4 counts of at least 200 cells per μL, estimated glomerular filtration rates of at least 70 mL per min, and HIV-1 genotypes showing sensitivity to emtricitabine and tenofovir. We excluded patients if they were hepatitis B-co-infected or hepatitis C-co-infected, had new AIDS-defining conditions within 30 days of screening, or were pregnant. We randomly allocated participants (2:1) to receive oral once-daily 75 mg bictegravir or 50 mg dolutegravir with matching placebo plus the fixed-dose combination of 200 mg emtricitabine and 25 mg tenofovir alafenamide for 48 weeks. We randomly allocated participants via an interactive web system, stratified by HIV-1 RNA concentration. Investigators, patients, study staff giving treatment, collecting data, and assessing outcomes, and the funder were masked to treatment group. The primary outcome was the proportion of participants with plasma HIV-1 RNA concentrations of less than 50 copies per mL at week 24 according to the US Food and Drug Administration-defined snapshot algorithm. We included all participants receiving one dose of study drug in analyses. This trial is registered with ClinicalTrials.gov, number NCT02397694.
Between March 23, 2015, and May 21, 2015, we screened 125 patients, randomly allocating and giving study drug to 98 (65 received bictegravir plus emtricitabine and tenofovir alafenamide and 33 received dolutegravir plus emtricitabine and tenofovir alafenamide). At week 24, 63 (96·9%) of 65 in the bictegravir group had HIV-1 RNA loads of less than 50 copies per mL compared with 31 (93·9%) of 33 in the dolutegravir group (weighted difference 2·9%, 95% CI -8·5 to 14·2; p=0·50). Treatment-emergent adverse events were reported by 55 (85%) of 65 participants in the bictegravir plus emtricitabine and tenofovir alafenamide group versus 22 (67%) of 33 in the dolutegravir plus emtricitabine and tenofovir alafenamide group. The most common adverse events were diarrhoea (eight [12%] of 65 vs four [12%] of 33) and nausea (five [8%] of 65 vs four [12%] of 33). One participant taking bictegravir plus emtricitabine and tenofovir alafenamide discontinued because of a drug-related adverse event (urticaria) after week 24. No treatment-related serious adverse events or deaths occurred.
Bictegravir plus emtricitabine and tenofovir alafenamide and dolutegravir plus emtricitabine and tenofovir alafenamide both showed high efficacy up to 24 weeks. Both treatments were well tolerated. Administration of bictegravir, a novel, potent, once-daily INSTI designed to improve on existing INSTI options with the backbone of emtricitabine and tenofovir alafenamide, might provide an advantage to patients.
- CfE Journal Club – Thursday September 7, 2017
Kate Salters presented the paper “Pregnancy incidence and intention after HIV diagnosis among women living with HIV in Canada”, which was published in PLOS One in July 2017. This paper is the first in Canada to look at trends in pregnancy incidence over time relative to cART uptake and intention of pregnancy.
Pregnancy incidence rates among women living with HIV (WLWH) have increased over time due to longer life expectancy, improved health status, and improved access to and HIV prevention benefits of combination antiretroviral therapy (cART). However, it is unclear whether intended or unintended pregnancies are contributing to observed increases.
We analyzed retrospective data from the Canadian HIV Women’s Sexual and Reproductive Health Cohort Study (CHIWOS). Kaplan-Meier methods and GEE Poisson models were used to measure cumulative incidence and incidence rate of pregnancy after HIV diagnosis overall, and by pregnancy intention. We used multivariable logistic regression models to examine independent correlates of unintended pregnancy among the most recent/current pregnancy.
Of 1,165 WLWH included in this analysis, 278 (23.9%) women reported 492 pregnancies after HIV diagnosis, 60.8% of which were unintended. Unintended pregnancy incidence (24.6 per 1,000 Women-Years (WYs); 95% CI: 21.0, 28.7) was higher than intended pregnancy incidence (16.6 per 1,000 WYs; 95% CI: 13.8, 20.1) (Rate Ratio: 1.5, 95% CI: 1.2–1.8). Pregnancy incidence among WLWH who initiated cART before or during pregnancy (29.1 per 1000 WYs with 95% CI: 25.1, 33.8) was higher than among WLWH not on cART during pregnancy (11.9 per 1000 WYs; 95% CI: 9.5, 14.9) (Rate Ratio: 2.4, 95% CI: 2.0–3.0). Women with current or recent unintended pregnancy (vs. intended pregnancy) had higher adjusted odds of being single (AOR: 1.94; 95% CI: 1.10, 3.42), younger at time of conception (AOR: 0.95 per year increase, 95% CI: 0.90, 0.99), and being born in Canada (AOR: 2.76, 95% CI: 1.55, 4.92).
Nearly one-quarter of women reported pregnancy after HIV diagnosis, with 61% of all pregnancies reported as unintended. Integrated HIV and reproductive health care programming is required to better support WLWH to optimize pregnancy planning and outcomes and to prevent unintended pregnancy.
- IDC Journal Club – Thursday October 19, 2017
Aynaa Alsharidi presented the paper “Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial” for the ONCMRK study group, which was published in Lancet HIV online first in September 11. This paper is the first randomized-controlled trail to assess the effectiveness and tolerability of once daily (1200 mg) raltegravir as compared to (400 mg) twice daily formulation in HIV-naïve infected patients.
Once daily regimens are preferred for HIV-1 treatment, to facilitate adherence and improve quality of life. We compared a new once daily formulation of raltegravir to the currently marketed twice daily formulation.
In this randomised, double-blind, parallel-group, phase 3, non-inferiority study, we enrolled participants aged 18 years or older with HIV-1 RNA of 1000 or more copies per mL and no previous antiretroviral treatment at 139 sites worldwide. We randomly assigned participants (2:1) via an interactive voice and web response system to raltegravir 1200 mg (two 600 mg tablets) orally once daily or raltegravir 400 mg (one tablet) orally twice daily, each with tenofovir disoproxil fumarate and emtricitabine orally once daily, for up to 96 weeks. A computer-generated allocation schedule stratified randomization by screening HIV-1 RNA value and co-infection with hepatitis B or C. Participants, sponsor personnel, investigators, and study site personnel involved in the treatment or evaluation of the participants were unaware of the treatment group assignments. The primary endpoint was the proportion of participants with HIV-1 RNA less than 40 copies per mL at week 48 assessed with the US Food and Drug Administration Snapshot algorithm. Non-inferiority was concluded if the lower bound of the two-sided 95% CI was greater than –10%. We assessed efficacy and safety in all participants who received one dose or more of study treatment. This study is registered with ClinicalTrials.gov, number NCT02131233.
Between May 26, 2014, and Dec 5, 2014, 802 participants were enrolled and randomly assigned, 533 to once daily treatment and 269 to twice daily; 797 received study therapy, 531 once daily and 266 twice daily. At week 48, 472 (89%) of 531 once daily recipients and 235 (88%) of 266 twice daily recipients achieved HIV-1 RNA less than 40 copies per mL (treatment difference 0•5%, 95% CI –4•2 to 5•2). Drug-related adverse events occurred in 130 (24%) of 531 participants in the once daily group (one of which was serious; none led to treatment discontinuation) and 68 (26%) of 266 participants in the twice daily group (two of which were serious; two led to treatment discontinuation). The most common drug-related adverse events were nausea (39 [7%] vs 18 [7%]), headache (16 [3%] vs 12 [5%]), and dizziness (12 [2%] vs eight [3%]). No treatment-related deaths were reported.
A once daily raltegravir 1200 mg regimen was non-inferior compared with raltegravir 400 mg twice daily for initial treatment of HIV-1 infection. These results support the use of raltegravir 1200 mg once daily for first-line therapy.
- CfE Journal Club – Thursday March 15, 2018
Stephanie Parent presented a paper titled: “Incidence, risk factors, and prevention of hepatitis C reinfection: a population-based cohort study”. This paper, published in 2016 by Islam and colleagues, examined hepatitis C (HCV) reinfection rates as well as correlates of reinfection in British Columbia in the interferon-era using the BC Testers Cohort administrative database. The authors reported an overall 8% reinfection among the entire study population, with an overall of reinfection rate of 1.27 (95% CI 1.15–1.39) per 100 person-years. Clearing the virus spontaneously, co-infection with HIV, and injection drug use were positively associated with HCV reinfection, whereas female sex, mental health counselling visits, and use of opioid substitution therapy among people who inject drugs were negatively correlated with reinfection. The presentation then discussed current strategies in place to characterise HCV reinfection and protection against reinfection in BC in the current era of universally covered direct-acting antivirals.
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.
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).
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).
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.