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Papers by Joel Singer

Research paper thumbnail of Management of non-severe pregnancy hypertension – A summary of the CHIPS Trial (Control of Hypertension in Pregnancy Study) research publications

Pregnancy Hypertension, Oct 1, 2019

The international CHIPS Trial (Control of Hypertension In Pregnancy Study) enrolled 987 women wit... more The international CHIPS Trial (Control of Hypertension In Pregnancy Study) enrolled 987 women with chronic (75%) or gestational (25%) hypertension. Pre-eclampsia developed in 48%; women remained on their allocated BP control and delivered an average of two weeks later. 'Less tight' control (target diastolic BP 100 mmHg) achieved BP that was 6/5mmHg higher (p < 0.001) than 'tight' control (target diastolic 85 mmHg, BP achieved 133/85 mmHg). 'Less tight' (vs. 'tight') control resulted in similar adverse perinatal outcomes (31.5% vs. 30.7%; p = 0.84) that balanced birthweight < 10th percentile (16.1% vs. 19.8%; p = 0.14) against preterm birth (35.6% vs. 31.5%; p = 0.18). 12-month follow-up revealed no compelling evidence for developmental programming of child growth. However, 'less tight' (vs. 'tight') control resulted in more severe maternal hypertension (40.6% vs. 27.5%; p < 0.001), and more women with platelets < 100 × 10 9 /L (4.3% vs. 1.6%; p = 0.02) or symptomatic elevated liver enzymes (4.3% vs. 1.8%; p = 0.03), with no difference in serious maternal complications (3.7% vs. 2.0%; p = 0.17). Labetalol was the drug of choice. Methyldopa did not result in inferior outcomes. Post-hoc, severe hypertension, independent of pre-eclampsia, was associated with heightened increased risk of adverse outcomes, and in 'less tight' control, of serious maternal complications. At no gestational age at initiation of BP control was 'less tight' superior to 'tight'. Women in both groups were equally satisfied with care. 'Less tight' control tended to be more expensive by CAD$6000 (p =0.07) based on neonatal care costs. Collectively, CHIPS publications have provided evidence that women with non-severe pregnancy hypertension should receive 'tight' BP control achieved by a simple algorithm.

Research paper thumbnail of Study protocol for a multicentre, prospective cohort study of the association of angiotensin II type 1 receptor blockers on outcomes of coronavirus infection

BMJ Open, Dec 1, 2020

Introduction The COVID-19 epidemic grows and there are clinical trials of antivirals. There is an... more Introduction The COVID-19 epidemic grows and there are clinical trials of antivirals. There is an opportunity to complement these trials with investigation of angiotensin II type 1 receptor blockers (ARBs) because an ARB (losartan) was effective in murine influenza pneumonia. Methods and analysis Our innovative design includes: ARBs; alignment with the WHO Ordinal Scale (primary endpoint) to align with other COVID-19 trials; joint longitudinal analysis; and predictive biomarkers (angiotensins I, 1-7, II and ACE1 and ACE2). Our hypothesis is: ARBs decrease the need for hospitalisation, severity (need for ventilation, vasopressors, extracorporeal membrane oxygenation or renal replacement therapy) or mortality of hospitalised COVID-19 infected adults. Our two-pronged multicentre pragmatic observational cohort study examines safety and effectiveness of ARBs in (1) hospitalised adult patients with COVID-19 and (2) outpatients already on or not on ARBs. The primary outcome will be evaluated by ordinal logistic regression and main secondary outcomes by both joint longitudinal modelling analyses. We will compare rates of hospitalisation of ARB-exposed versus not ARB-exposed patients. We will also determine whether continuing ARBs or not decreases the primary outcome. Based on published COVID-19 cohorts, assuming 15% of patients are ARB-exposed, a total sample size of 497 patients can detect a proportional OR of 0.5 (alpha=0.05, 80% power) comparing WHO scale of ARBexposed versus non-ARB-exposed patients. Ethics and dissemination This study has core institution approval (

Research paper thumbnail of Outcomes and characteristics of patients hospitalized for COVID-19 in British Columbia, Ontario and Quebec during the Omicron wave

CMAJ Open

micron, the predominant variant of concern of SARS-CoV-2, 1 is more transmissible but does not in... more micron, the predominant variant of concern of SARS-CoV-2, 1 is more transmissible but does not increase-and even decreases 2,3-risks of hospitalization 4-7 and death 8,9 compared with previous variants. From March 2020 to July 2022, COVID-19 waves in Canada 10 were driven by wild-type, Alpha, Delta and Omicron variants, and mortality decreased after wave 1 8,9,11-16 except in hospitalized patients aged 65 years or older in Ontario. 17 Mortality of patients hospitalized during previous COVID-19 waves in Canada 16 had decreased from waves 1 to 3 because of differing demographic characteristics, management (e.g., dexamethasone use, other COVID-19 therapies 18,19) and vaccines. 20 Overall, Omicron fatality rates decreased community wide. 8,9 This study focuses on patients hospitalized with COVID-19 in 3 Canadian provinces (British Columbia, Ontario and Quebec) during the Omicron and first 3 waves. Our objectives were to compare outcomes of patients in the Omicron wave by vaccination status, and also to compare outcomes between patients hospitalized during the Omicron wave and patients in previous waves.

Research paper thumbnail of Oral micronized progesterone for perimenopausal night sweats and hot flushes a Phase III Canada-wide randomized placebo-controlled 4 month trial

Scientific Reports

This study tested progesterone for perimenopausal hot flush ± night sweat (vasomotor symptom, VMS... more This study tested progesterone for perimenopausal hot flush ± night sweat (vasomotor symptom, VMS) treatment. It was a double-blind, randomized trial of 300 mg oral micronized progesterone@bedtime versus placebo for 3-months (m) after a 1-m untreated baseline during 2012/1–2017/4. We randomized untreated, non-depressed, screen- and baseline-eligible by VMS, perimenopausal women (with flow within 1-year), ages 35–58 (n = 189). Participants aged 50 (± SD = 4.6) were mostly White, educated, minimally overweight with 63% in late perimenopause; 93% participated remotely. The 1° outcome was 3rd-m VMS Score difference. Participants recorded VMS number and intensity (0–4 scale)/24 h on a VMS Calendar. Randomization required VMS (intensity 2–4/4) of sufficient frequency and/or ≥ 2/week night sweat awakenings. Baseline total VMS Score (SD) was 12.2 (11.3) without assignment difference. Third-m VMS Score did not differ by therapy (Rate Difference − 1.51). However, the 95% CI [− 3.97, 0.95] P =...

Research paper thumbnail of Community-integrated self-collected HPV-based cervix screening in a low-resource rural setting: a pragmatic, cluster-randomized trial

Nature Medicine

Effective approaches to improve coverage of self-collected human papillomavirus (HPV)-based cervi... more Effective approaches to improve coverage of self-collected human papillomavirus (HPV)-based cervix screening (SCS) as well as attendance at treatment for HPV-positive participants are needed to inform policy on optimal integration of cervical cancer screening programs within existing infrastructure in low-resource settings. ASPIRE Mayuge was a pragmatic cluster-randomized trial in rural Mayuge district, Uganda, comparing the superiority of two recruitment implementation strategies for SCS: Door-to-Door versus Community Health Day. Villages were randomized (unblinded) to a strategy, and participants aged 25-49 years with no previous history of hysterectomy or treatment for cervical cancer or pre-cancer were eligible. Participants completed a survey and participated in SCS. The primary outcome was rate of attendance at treatment after a positive SCS. The trial randomized 31 villages and 2,019 participants included in these analyses (Door-to-Door: 16 clusters, 1,055 participants; Community Health Day: 15 clusters, 964 participants). Among HPV-positive participants, attendance at treatment rates were 75% (Door-to-Door) and 67% (Community Health Day) (P = 0.049). Participants in the Community Health Day intervention were less likely to attend treatment compared to Door-to-Door (risk ratio = 0.78, 95% confidence interval: 0.64-0.96). No adverse events were reported. Policymakers in low-resource settings can use these results to guide implementation of SCS programs. ISRCTN registration: 12767014. ClinicalTrials.gov registration: NCT04000503.

Research paper thumbnail of Type and timing of antiretroviral therapy during pregnancy: Impact on risk of preterm delivery and small‐for‐gestational age births in Canada, a retrospective cohort study

International Journal of Gynecology & Obstetrics

ObjectiveTo evaluate the impact of type and timing of antiretroviral therapy (ART) on the risk of... more ObjectiveTo evaluate the impact of type and timing of antiretroviral therapy (ART) on the risk of preterm delivery (PTD) and small‐for‐gestational age (SGA) birth among pregnant women and people living with HIV in Canada.MethodsData for this retrospective cohort study were analyzed from the Canadian Perinatal HIV Surveillance Program from 1990 to 2020. The association between ART and risk of PTD (<37 weeks) and SGA birth (<10th percentile) was explored using mixed effects logistic regression and time‐dependent Cox proportional hazards models.ResultsOverall, there were 14.9% (654 of 4379) PTD and 18.5% (732 of 3947) SGA cases. A higher risk of PTD was observed with nonnucleoside reverse transcriptase inhibitor–(adjusted hazard ratio [aHR], 1.73; P = 0.019) and boosted protease inhibitor– (aHR, 186; P = 0.007) based regimens compared with integrase strand transfer inhibitor (INSTI)–based regimens. ART initiation prior to conception was associated with a lower risk of SGA birth c...

Research paper thumbnail of BEING: Bone Health in Aging Women with HIV: Impact of Switching Antiretroviral Therapy on Bone Mineral Density During the Perimenopausal Period

AIDS Research and Human Retroviruses

Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretr... more Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretroviral therapy (ART). Our goal was to study the impact of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on bone mineral density (BMD) in peri-and early postmenopausal women living with HIV. This is a randomized international multicenter study of an early versus delayed (48-week) switch. BMD was measured by dual energy X-ray absorptiometry scan. Thirty-four women were enrolled: 19 in the immediate and 15 in the delayed switch arm from September 2017 to April 2019; 30 completed the 96-week protocol. The study closed for futility during the COVID-19 pandemic. The median (intraquartile range [IQR]) age was 51 years (47, 53), with a median (IQR) of 16.5 years (14, 23) since HIV diagnosis, median (IQR) 14 years (11, 20) of ART, and mean 8.6 years TDF. At enrollment, TDF was used in combination with a boosted protease inhibitor (n = 7), a non-nucleoside reverse transcriptase inhibitor (n = 13), an integrase inhibitor (n = 11), or more than one ART class (n = 3). The median (95% confidence interval [CI]) percentage change in BMD at the lumbar spine from 0 to 48 weeks in the immediate switch group was 1.97% (-1.15 to 5.49) compared with a median (95% CI) decrease of 2.32% (-5.11 to 0.19) in the delayed arm. The median (95% CI) percentage change in BMD from 0 to 96 weeks was 2.33% (0-4.51) in the immediate arm compared with 0.70% (-3.19 to 2.47) in the delayed arm. We demonstrated a trend to increased BMD at the lumbar spine after a switch from TDF to TAF in peri-and early postmenopausal women living with HIV. Clinical Trials.gov: NCT02815566.

Research paper thumbnail of COVID-19 vaccine immunogenicity in people with HIV

AIDS

Objectives: Many vaccines require higher/additional doses or adjuvants to provide adequate protec... more Objectives: Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people with HIV (PWH). Our objective was to compare COVID-19 vaccine immunogenicity in PWH to HIV-negative individuals. Design: In a Canadian multi-center prospective, observational cohort of PWH receiving at least two COVID-19 vaccinations, we measured vaccine-induced immunity at 3 and 6 months post 2nd and 1-month post 3rd doses. Methods: The primary outcome was the percentage of PWH mounting vaccine-induced immunity [co-positivity for anti-IgG against SARS-CoV2 Spike(S) and receptor-binding domain proteins] 6 months post 2nd dose. Univariable and multivariable logistic regressions were used to compare COVID-19-specific immune responses between groups and within subgroups. Results: Data from 294 PWH and 267 controls were analyzed. Immunogenicity was achieved in over 90% at each time point in both groups. The proportions of participants achieving comparable anti-receptor-bindin...

Research paper thumbnail of Safety and Tolerability of Oral Cannabinoids in People Living with HIV on Long-Term ART: A Randomized, Open-Label, Interventional Pilot Clinical Trial (CTNPT 028)

Biomedicines

Background: With anti-inflammatory properties, cannabinoids may be a potential strategy to reduce... more Background: With anti-inflammatory properties, cannabinoids may be a potential strategy to reduce immune activation in people living with HIV (PLWH) but more information on their safety and tolerability is needed. Methods: We conducted an open-label interventional pilot study at the McGill University Health Centre in Montreal, Canada. PLWH were randomized to oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (THC 2.5 mg/CBD 2.5 mg) or CBD-only capsules (CBD 200 mg). Individuals titrated doses as tolerated to a maximum daily dose THC 15 mg/CBD 15 mg or 800 mg CBD, respectively, for 12 weeks. The primary outcome was the percentage of participants without any significant toxicity based on the WHO toxicity scale (Grades 0–2 scores). Results: Out of ten individuals, eight completed the study. Two from the CBD-only arm were withdrawn for safety concerns: phlebotomy aggravating pre-existing anemia and severe hepatitis on 800 mg CBD with newly discovered pancreatic adenocarci...

Research paper thumbnail of Prescribing patterns of antiretroviral treatments during pregnancy for women living with HIV in Canada 2004–2020: A surveillance study

HIV Medicine

BackgroundWhile treatment guidelines for HIV in adults have evolved rapidly with the advent of ne... more BackgroundWhile treatment guidelines for HIV in adults have evolved rapidly with the advent of new antiretroviral (ARV) treatment, those for the prevention of vertical HIV transmission in pregnancy have evolved more slowly due to safety and efficacy concerns. Here we describe Canadian prescribing patterns for ARV treatments during pregnancy and compare them to perinatal HIV prescribing guidelines of the United States Department of Health and Human Services (HHS), that are commonly used in Canada and include recommendations for newly commercialized therapies.MethodsThe Canadian Perinatal HIV Surveillance Program (CPHSP) captures annual medical data on mothers living with HIV and their infants from 23 sites across Canada. Women from this cohort who received an ARV treatment during pregnancy and who gave birth between 2004 and 2020 were included in the study. ARV treatments were designated as ‘preferred/alternative’ as per HHS HIV perinatal guidelines, or ‘other than preferred/alternat...

Research paper thumbnail of Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19*

Critical Care Medicine

OBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting e... more OBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components. DESIGN: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup (n = 46), recorded d-dimer (n = 967), compar...

Research paper thumbnail of Organ dysfunction and death in patients admitted to hospital with COVID-19 in pandemic waves 1 to 3 in British Columbia, Ontario and Quebec, Canada: a cohort study

CMAJ Open

T here have been 5 waves of the COVID-19 pandemic in Canada, including the omicron-driven wave (a... more T here have been 5 waves of the COVID-19 pandemic in Canada, including the omicron-driven wave (as of Dec. 17, 2021 1). Mortality from COVID-19 varied as the waves moved across the world, and changes in patient mix, the emergence of successful treatment and improvements in quality of care affected acute COVID-19 mortality. Some studies showed decreased mortality after wave 1. 2,3 In a 43-country study, 3 there was lower mortality in wave 2 than in wave 1. Domingo and colleagues 4 found higher mortality among patients in Spain in wave 1 than in wave 2 that was explained by differences in intensive care unit (ICU) admission and ventilation use. In another study, with data from 14 countries that each had at least 4000 deaths from COVID-19 as of Jan. 14, 2021, the age distribution of those who died was similar between waves 1 and 2, but there were fewer deaths among nursing home residents in wave 2. 5 More use of anticoagulation and corticosteroids in wave 2 may explain the lower mortality. 6 In Spain, patients from wave 2 were more

Research paper thumbnail of Oral Micronized Progesterone for Perimenopausal Night Sweats and Hot Flushes: A 12-Week Randomized Phase III Canada-Wide Clinical Trial

SSRN Electronic Journal, 2020

Background: Oral micronized progesterone (progesterone) has been shown superior to placebo for va... more Background: Oral micronized progesterone (progesterone) has been shown superior to placebo for vasomotor symptoms (VMS, night sweats and/or hot flushes) in menopausal women (>1 year after final flow). A VMS Score difference ≥3 was clinically important. VMS begin in perimenopause; however, all but two VMS randomized placebo-controlled trials (RCT) were in menopausal women. No well-performed RCT has proven any therapy to be effective for perimenopausal VMS. Methods: To test progesterone for perimenopausal VMS, we ran a quadruple masked, randomized (1:1), placebo-controlled trial (2012-2016) with 28-day run-in and 84 days’ experimental phases. Our academic medical centre recruited locally/nationally for women ages 35-58 with cycle irregularity but menstruation within 12 months plus untreated, problematic VMS. Our primary, intent-to-treat outcome was participant-recorded daily VMS Score ([# night sweats x intensity]+[#daytime hot flushes x intensity]) days 56-84, adjusted for run-in VMS Score. Our secondary outcome was Women’s Perceived VMS Change (-5 to +5) on day 84. Findings: We randomized 189 women of mean (SD) age 49·9 (4·6) years to progesterone, 300 mg/bedtime [n=93], vs placebo [n=96]. The mean run-in VMS Score (n=189) was 12·2 (11·3). VMS Scores days 56-84 were not different by progesterone vs placebo (Rate Ratio [RR] 0·79 [95% CI 0·54, 1·15]; Rate Difference [RD] -1·51 [95% CI -3·97, 0·95]; P=0·222). RD 95% CI included -3, thus did not exclude a clinically important effect. Perceived VMS Change indicated progesterone significantly improved night sweats over placebo (-3 vs -2, P=0·023). No serious adverse events occurred. Interpretation: Progesterone-treated perimenopausal women perceived significantly improved night sweats. These results show trends toward clinically important VMS benefits from perimenopausal progesterone. Given the previously undocumented high perimenopausal VMS variability, a larger RCT of progesterone for perimenopause VMS is still needed. Trial Registered: ClinicalTrials.gov NCT0146469. Funding Statement: Funded by a grant from the Canadian Institutes for Health Research (#MOP106644). Extended enrollment was funded by an arms-length unrestricted grant to the Centre for Menstrual Cycle and Ovulation Research of the University of British Columbia from Besins Healthcare International. Declaration of Interests: None of the investigators, co-investigators or collaborators in this RCT has a financial or other conflict of interest with these data or other ethical conflicts. Ethics Approval Statement: The University of British Columbia Clinical Research Ethics Board approved this protocol and its amendments.

Research paper thumbnail of The impact of pre‐eclampsia definitions on the identification of adverse outcome risk in hypertensive pregnancy – analyses from the CHIPS trial (Control of Hypertension in Pregnancy Study)

BJOG: An International Journal of Obstetrics & Gynaecology, 2021

ObjectiveTo examine the association between pre‐eclampsia definition and pregnancy outcome.Design... more ObjectiveTo examine the association between pre‐eclampsia definition and pregnancy outcome.DesignSecondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data.SettingInternational multicentre randomised controlled trial (RCT).PopulationIn all, 987 women with non‐severe non‐proteinuric pregnancy hypertension.MethodsWe evaluated the association between pre‐eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control.Main outcome measuresMain CHIPS trial outcomes: primary (perinatal loss or high‐level neonatal care for >48 hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, delivery at <34 or <37 weeks, and maternal hospitalisation before birth.ResultsOf 979/987 women with informative data, 280 (28.6%) progressed to pre‐eclampsia defined restrictively by new proteinuria, and 471 (48.1%) to pre‐eclampsia defined broadly as proteinuria or one/more...

Research paper thumbnail of Sustained Dysregulation of the Plasma Renin-angiotensin System in Acute COVID-19

SARS-CoV-2 enters cells by binding to angiotensin-converting enzyme 2 (ACE2), and COVID-19 infect... more SARS-CoV-2 enters cells by binding to angiotensin-converting enzyme 2 (ACE2), and COVID-19 infection may therefore induce changes in the renin-angiotensin system (RAS). To determine the effects of COVID-19 on plasma RAS components, we measured plasma ACE, ACE2, and angiotensins I, (1-7), and II in 46 adults with COVID-19 at hospital admission and on days 2, 4, 7 and 14, compared to 50 blood donors (controls). We compared survivors vs. non-survivors, males vs. females, ventilated vs. not ventilated, and angiotensin receptor blocker (ARB) and angiotensin-converting enzyme (ACE) inhibitor-exposed vs. not exposed. At admission, COVID-19 patients had higher plasma levels of ACE (p=0.012), ACE2 (p=0.001) and angiotensin-(1-7) (p<0.001) than controls. Plasma ACE and ACE2 remained elevated for 14 days in COVID-19 patients, while plasma angiotensin-(1-7) decreased after 7 days. In adjusted analyses, plasma ACE was higher in males vs. females (p=0.042), and plasma angiotensin I was signifi...

Research paper thumbnail of Elevated Blood Mitochondrial DNA in Early Life Among Uninfected Children Exposed to Human Immunodeficiency Virus and Combination Antiretroviral Therapy in utero

The Journal of Infectious Diseases, 2020

BackgroundCombination antiretroviral therapy (cART) during pregnancy prevents vertical transmissi... more BackgroundCombination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life.MethodsWhole-blood mtDNA content at birth and in early life (age 0–3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated.ResultsAt birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged dur...

Research paper thumbnail of Congenital anomalies following antenatal exposure to dolutegravir: a Canadian surveillance study

BJOG: An International Journal of Obstetrics & Gynaecology, 2019

ObjectiveDolutegravir is recommended worldwide as a first‐line antiretroviral therapy (ART) for i... more ObjectiveDolutegravir is recommended worldwide as a first‐line antiretroviral therapy (ART) for individuals living with HIV. A recent study reported increased rates of neural tube defects in infants of dolutegravir‐treated women. This study examined rates of congenital anomalies in infants born to women living with HIV (WLWH) in Canada.DesignThe Canadian Perinatal HIV Surveillance Programme captures surveillance data on pregnant WLWH and their babies and was analysed to examine the incidence of congenital anomalies.SettingPaediatric HIV clinics.PopulationLive‐born infants born in Canada to WLWH between 2007 and 2017.MethodsData on mother–infant pairs, including maternal ART use at conception and during pregnancy, are collected by participating sites.Main outcome measuresCongenital anomalies.ResultsOf the 2423 WLWH, 85 (3.5%, 95% CI 2.85–4.36%) had non‐chromosomal congenital anomalies. There was no evidence of a significant difference in rates of congenital anomalies between women wh...

Research paper thumbnail of Oral cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028—study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune activation

BMJ Open, 2019

IntroductionDespite antiretroviral therapy (ART), people living with HIV have higher rates of non... more IntroductionDespite antiretroviral therapy (ART), people living with HIV have higher rates of non-infectious chronic diseases. These conditions are driven by relatively high levels of inflammation persisting on ART compared with uninfected individuals. Chronic inflammation also contributes to HIV persistence during ART. Cannabis when taken orally may represent a way to reduce inflammation and strengthen immune responses. Before planning large interventional studies, it is important to ensure that cannabis taken orally is safe and well tolerated in people living with HIV. We propose to conduct a pilot randomised trial to examine the safety and tolerability of cannabis oils containing tetrahydrocannabinol (THC) and cannabidiol (CBD) consumed orally in people living with HIV. We will also measure inflammatory markers, markers of HIV persistence in peripheral blood cells and changes in the gastrointestinal microbiome.Methods and analysisTwenty-six people living with HIV having undetecta...

Research paper thumbnail of 1614High Rates of Preterm Birth and Small for Gestational Age in a Cohort of HIV Infected Women in Canada: Role of Ritonavir Boosted Regimens?

Open Forum Infectious Diseases, 2014

Research paper thumbnail of O18.5 Examining hpv prevalence and uptake of cervical cancer screening among hiv positive and negative women participating in a pilot rct in uganda comparing self-collection based hpv testing to via

Sexually Transmitted Infections, 2015

Research paper thumbnail of Management of non-severe pregnancy hypertension – A summary of the CHIPS Trial (Control of Hypertension in Pregnancy Study) research publications

Pregnancy Hypertension, Oct 1, 2019

The international CHIPS Trial (Control of Hypertension In Pregnancy Study) enrolled 987 women wit... more The international CHIPS Trial (Control of Hypertension In Pregnancy Study) enrolled 987 women with chronic (75%) or gestational (25%) hypertension. Pre-eclampsia developed in 48%; women remained on their allocated BP control and delivered an average of two weeks later. 'Less tight' control (target diastolic BP 100 mmHg) achieved BP that was 6/5mmHg higher (p < 0.001) than 'tight' control (target diastolic 85 mmHg, BP achieved 133/85 mmHg). 'Less tight' (vs. 'tight') control resulted in similar adverse perinatal outcomes (31.5% vs. 30.7%; p = 0.84) that balanced birthweight < 10th percentile (16.1% vs. 19.8%; p = 0.14) against preterm birth (35.6% vs. 31.5%; p = 0.18). 12-month follow-up revealed no compelling evidence for developmental programming of child growth. However, 'less tight' (vs. 'tight') control resulted in more severe maternal hypertension (40.6% vs. 27.5%; p < 0.001), and more women with platelets < 100 × 10 9 /L (4.3% vs. 1.6%; p = 0.02) or symptomatic elevated liver enzymes (4.3% vs. 1.8%; p = 0.03), with no difference in serious maternal complications (3.7% vs. 2.0%; p = 0.17). Labetalol was the drug of choice. Methyldopa did not result in inferior outcomes. Post-hoc, severe hypertension, independent of pre-eclampsia, was associated with heightened increased risk of adverse outcomes, and in 'less tight' control, of serious maternal complications. At no gestational age at initiation of BP control was 'less tight' superior to 'tight'. Women in both groups were equally satisfied with care. 'Less tight' control tended to be more expensive by CAD$6000 (p =0.07) based on neonatal care costs. Collectively, CHIPS publications have provided evidence that women with non-severe pregnancy hypertension should receive 'tight' BP control achieved by a simple algorithm.

Research paper thumbnail of Study protocol for a multicentre, prospective cohort study of the association of angiotensin II type 1 receptor blockers on outcomes of coronavirus infection

BMJ Open, Dec 1, 2020

Introduction The COVID-19 epidemic grows and there are clinical trials of antivirals. There is an... more Introduction The COVID-19 epidemic grows and there are clinical trials of antivirals. There is an opportunity to complement these trials with investigation of angiotensin II type 1 receptor blockers (ARBs) because an ARB (losartan) was effective in murine influenza pneumonia. Methods and analysis Our innovative design includes: ARBs; alignment with the WHO Ordinal Scale (primary endpoint) to align with other COVID-19 trials; joint longitudinal analysis; and predictive biomarkers (angiotensins I, 1-7, II and ACE1 and ACE2). Our hypothesis is: ARBs decrease the need for hospitalisation, severity (need for ventilation, vasopressors, extracorporeal membrane oxygenation or renal replacement therapy) or mortality of hospitalised COVID-19 infected adults. Our two-pronged multicentre pragmatic observational cohort study examines safety and effectiveness of ARBs in (1) hospitalised adult patients with COVID-19 and (2) outpatients already on or not on ARBs. The primary outcome will be evaluated by ordinal logistic regression and main secondary outcomes by both joint longitudinal modelling analyses. We will compare rates of hospitalisation of ARB-exposed versus not ARB-exposed patients. We will also determine whether continuing ARBs or not decreases the primary outcome. Based on published COVID-19 cohorts, assuming 15% of patients are ARB-exposed, a total sample size of 497 patients can detect a proportional OR of 0.5 (alpha=0.05, 80% power) comparing WHO scale of ARBexposed versus non-ARB-exposed patients. Ethics and dissemination This study has core institution approval (

Research paper thumbnail of Outcomes and characteristics of patients hospitalized for COVID-19 in British Columbia, Ontario and Quebec during the Omicron wave

CMAJ Open

micron, the predominant variant of concern of SARS-CoV-2, 1 is more transmissible but does not in... more micron, the predominant variant of concern of SARS-CoV-2, 1 is more transmissible but does not increase-and even decreases 2,3-risks of hospitalization 4-7 and death 8,9 compared with previous variants. From March 2020 to July 2022, COVID-19 waves in Canada 10 were driven by wild-type, Alpha, Delta and Omicron variants, and mortality decreased after wave 1 8,9,11-16 except in hospitalized patients aged 65 years or older in Ontario. 17 Mortality of patients hospitalized during previous COVID-19 waves in Canada 16 had decreased from waves 1 to 3 because of differing demographic characteristics, management (e.g., dexamethasone use, other COVID-19 therapies 18,19) and vaccines. 20 Overall, Omicron fatality rates decreased community wide. 8,9 This study focuses on patients hospitalized with COVID-19 in 3 Canadian provinces (British Columbia, Ontario and Quebec) during the Omicron and first 3 waves. Our objectives were to compare outcomes of patients in the Omicron wave by vaccination status, and also to compare outcomes between patients hospitalized during the Omicron wave and patients in previous waves.

Research paper thumbnail of Oral micronized progesterone for perimenopausal night sweats and hot flushes a Phase III Canada-wide randomized placebo-controlled 4 month trial

Scientific Reports

This study tested progesterone for perimenopausal hot flush ± night sweat (vasomotor symptom, VMS... more This study tested progesterone for perimenopausal hot flush ± night sweat (vasomotor symptom, VMS) treatment. It was a double-blind, randomized trial of 300 mg oral micronized progesterone@bedtime versus placebo for 3-months (m) after a 1-m untreated baseline during 2012/1–2017/4. We randomized untreated, non-depressed, screen- and baseline-eligible by VMS, perimenopausal women (with flow within 1-year), ages 35–58 (n = 189). Participants aged 50 (± SD = 4.6) were mostly White, educated, minimally overweight with 63% in late perimenopause; 93% participated remotely. The 1° outcome was 3rd-m VMS Score difference. Participants recorded VMS number and intensity (0–4 scale)/24 h on a VMS Calendar. Randomization required VMS (intensity 2–4/4) of sufficient frequency and/or ≥ 2/week night sweat awakenings. Baseline total VMS Score (SD) was 12.2 (11.3) without assignment difference. Third-m VMS Score did not differ by therapy (Rate Difference − 1.51). However, the 95% CI [− 3.97, 0.95] P =...

Research paper thumbnail of Community-integrated self-collected HPV-based cervix screening in a low-resource rural setting: a pragmatic, cluster-randomized trial

Nature Medicine

Effective approaches to improve coverage of self-collected human papillomavirus (HPV)-based cervi... more Effective approaches to improve coverage of self-collected human papillomavirus (HPV)-based cervix screening (SCS) as well as attendance at treatment for HPV-positive participants are needed to inform policy on optimal integration of cervical cancer screening programs within existing infrastructure in low-resource settings. ASPIRE Mayuge was a pragmatic cluster-randomized trial in rural Mayuge district, Uganda, comparing the superiority of two recruitment implementation strategies for SCS: Door-to-Door versus Community Health Day. Villages were randomized (unblinded) to a strategy, and participants aged 25-49 years with no previous history of hysterectomy or treatment for cervical cancer or pre-cancer were eligible. Participants completed a survey and participated in SCS. The primary outcome was rate of attendance at treatment after a positive SCS. The trial randomized 31 villages and 2,019 participants included in these analyses (Door-to-Door: 16 clusters, 1,055 participants; Community Health Day: 15 clusters, 964 participants). Among HPV-positive participants, attendance at treatment rates were 75% (Door-to-Door) and 67% (Community Health Day) (P = 0.049). Participants in the Community Health Day intervention were less likely to attend treatment compared to Door-to-Door (risk ratio = 0.78, 95% confidence interval: 0.64-0.96). No adverse events were reported. Policymakers in low-resource settings can use these results to guide implementation of SCS programs. ISRCTN registration: 12767014. ClinicalTrials.gov registration: NCT04000503.

Research paper thumbnail of Type and timing of antiretroviral therapy during pregnancy: Impact on risk of preterm delivery and small‐for‐gestational age births in Canada, a retrospective cohort study

International Journal of Gynecology & Obstetrics

ObjectiveTo evaluate the impact of type and timing of antiretroviral therapy (ART) on the risk of... more ObjectiveTo evaluate the impact of type and timing of antiretroviral therapy (ART) on the risk of preterm delivery (PTD) and small‐for‐gestational age (SGA) birth among pregnant women and people living with HIV in Canada.MethodsData for this retrospective cohort study were analyzed from the Canadian Perinatal HIV Surveillance Program from 1990 to 2020. The association between ART and risk of PTD (<37 weeks) and SGA birth (<10th percentile) was explored using mixed effects logistic regression and time‐dependent Cox proportional hazards models.ResultsOverall, there were 14.9% (654 of 4379) PTD and 18.5% (732 of 3947) SGA cases. A higher risk of PTD was observed with nonnucleoside reverse transcriptase inhibitor–(adjusted hazard ratio [aHR], 1.73; P = 0.019) and boosted protease inhibitor– (aHR, 186; P = 0.007) based regimens compared with integrase strand transfer inhibitor (INSTI)–based regimens. ART initiation prior to conception was associated with a lower risk of SGA birth c...

Research paper thumbnail of BEING: Bone Health in Aging Women with HIV: Impact of Switching Antiretroviral Therapy on Bone Mineral Density During the Perimenopausal Period

AIDS Research and Human Retroviruses

Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretr... more Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretroviral therapy (ART). Our goal was to study the impact of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on bone mineral density (BMD) in peri-and early postmenopausal women living with HIV. This is a randomized international multicenter study of an early versus delayed (48-week) switch. BMD was measured by dual energy X-ray absorptiometry scan. Thirty-four women were enrolled: 19 in the immediate and 15 in the delayed switch arm from September 2017 to April 2019; 30 completed the 96-week protocol. The study closed for futility during the COVID-19 pandemic. The median (intraquartile range [IQR]) age was 51 years (47, 53), with a median (IQR) of 16.5 years (14, 23) since HIV diagnosis, median (IQR) 14 years (11, 20) of ART, and mean 8.6 years TDF. At enrollment, TDF was used in combination with a boosted protease inhibitor (n = 7), a non-nucleoside reverse transcriptase inhibitor (n = 13), an integrase inhibitor (n = 11), or more than one ART class (n = 3). The median (95% confidence interval [CI]) percentage change in BMD at the lumbar spine from 0 to 48 weeks in the immediate switch group was 1.97% (-1.15 to 5.49) compared with a median (95% CI) decrease of 2.32% (-5.11 to 0.19) in the delayed arm. The median (95% CI) percentage change in BMD from 0 to 96 weeks was 2.33% (0-4.51) in the immediate arm compared with 0.70% (-3.19 to 2.47) in the delayed arm. We demonstrated a trend to increased BMD at the lumbar spine after a switch from TDF to TAF in peri-and early postmenopausal women living with HIV. Clinical Trials.gov: NCT02815566.

Research paper thumbnail of COVID-19 vaccine immunogenicity in people with HIV

AIDS

Objectives: Many vaccines require higher/additional doses or adjuvants to provide adequate protec... more Objectives: Many vaccines require higher/additional doses or adjuvants to provide adequate protection for people with HIV (PWH). Our objective was to compare COVID-19 vaccine immunogenicity in PWH to HIV-negative individuals. Design: In a Canadian multi-center prospective, observational cohort of PWH receiving at least two COVID-19 vaccinations, we measured vaccine-induced immunity at 3 and 6 months post 2nd and 1-month post 3rd doses. Methods: The primary outcome was the percentage of PWH mounting vaccine-induced immunity [co-positivity for anti-IgG against SARS-CoV2 Spike(S) and receptor-binding domain proteins] 6 months post 2nd dose. Univariable and multivariable logistic regressions were used to compare COVID-19-specific immune responses between groups and within subgroups. Results: Data from 294 PWH and 267 controls were analyzed. Immunogenicity was achieved in over 90% at each time point in both groups. The proportions of participants achieving comparable anti-receptor-bindin...

Research paper thumbnail of Safety and Tolerability of Oral Cannabinoids in People Living with HIV on Long-Term ART: A Randomized, Open-Label, Interventional Pilot Clinical Trial (CTNPT 028)

Biomedicines

Background: With anti-inflammatory properties, cannabinoids may be a potential strategy to reduce... more Background: With anti-inflammatory properties, cannabinoids may be a potential strategy to reduce immune activation in people living with HIV (PLWH) but more information on their safety and tolerability is needed. Methods: We conducted an open-label interventional pilot study at the McGill University Health Centre in Montreal, Canada. PLWH were randomized to oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (THC 2.5 mg/CBD 2.5 mg) or CBD-only capsules (CBD 200 mg). Individuals titrated doses as tolerated to a maximum daily dose THC 15 mg/CBD 15 mg or 800 mg CBD, respectively, for 12 weeks. The primary outcome was the percentage of participants without any significant toxicity based on the WHO toxicity scale (Grades 0–2 scores). Results: Out of ten individuals, eight completed the study. Two from the CBD-only arm were withdrawn for safety concerns: phlebotomy aggravating pre-existing anemia and severe hepatitis on 800 mg CBD with newly discovered pancreatic adenocarci...

Research paper thumbnail of Prescribing patterns of antiretroviral treatments during pregnancy for women living with HIV in Canada 2004–2020: A surveillance study

HIV Medicine

BackgroundWhile treatment guidelines for HIV in adults have evolved rapidly with the advent of ne... more BackgroundWhile treatment guidelines for HIV in adults have evolved rapidly with the advent of new antiretroviral (ARV) treatment, those for the prevention of vertical HIV transmission in pregnancy have evolved more slowly due to safety and efficacy concerns. Here we describe Canadian prescribing patterns for ARV treatments during pregnancy and compare them to perinatal HIV prescribing guidelines of the United States Department of Health and Human Services (HHS), that are commonly used in Canada and include recommendations for newly commercialized therapies.MethodsThe Canadian Perinatal HIV Surveillance Program (CPHSP) captures annual medical data on mothers living with HIV and their infants from 23 sites across Canada. Women from this cohort who received an ARV treatment during pregnancy and who gave birth between 2004 and 2020 were included in the study. ARV treatments were designated as ‘preferred/alternative’ as per HHS HIV perinatal guidelines, or ‘other than preferred/alternat...

Research paper thumbnail of Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19*

Critical Care Medicine

OBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting e... more OBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components. DESIGN: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup (n = 46), recorded d-dimer (n = 967), compar...

Research paper thumbnail of Organ dysfunction and death in patients admitted to hospital with COVID-19 in pandemic waves 1 to 3 in British Columbia, Ontario and Quebec, Canada: a cohort study

CMAJ Open

T here have been 5 waves of the COVID-19 pandemic in Canada, including the omicron-driven wave (a... more T here have been 5 waves of the COVID-19 pandemic in Canada, including the omicron-driven wave (as of Dec. 17, 2021 1). Mortality from COVID-19 varied as the waves moved across the world, and changes in patient mix, the emergence of successful treatment and improvements in quality of care affected acute COVID-19 mortality. Some studies showed decreased mortality after wave 1. 2,3 In a 43-country study, 3 there was lower mortality in wave 2 than in wave 1. Domingo and colleagues 4 found higher mortality among patients in Spain in wave 1 than in wave 2 that was explained by differences in intensive care unit (ICU) admission and ventilation use. In another study, with data from 14 countries that each had at least 4000 deaths from COVID-19 as of Jan. 14, 2021, the age distribution of those who died was similar between waves 1 and 2, but there were fewer deaths among nursing home residents in wave 2. 5 More use of anticoagulation and corticosteroids in wave 2 may explain the lower mortality. 6 In Spain, patients from wave 2 were more

Research paper thumbnail of Oral Micronized Progesterone for Perimenopausal Night Sweats and Hot Flushes: A 12-Week Randomized Phase III Canada-Wide Clinical Trial

SSRN Electronic Journal, 2020

Background: Oral micronized progesterone (progesterone) has been shown superior to placebo for va... more Background: Oral micronized progesterone (progesterone) has been shown superior to placebo for vasomotor symptoms (VMS, night sweats and/or hot flushes) in menopausal women (>1 year after final flow). A VMS Score difference ≥3 was clinically important. VMS begin in perimenopause; however, all but two VMS randomized placebo-controlled trials (RCT) were in menopausal women. No well-performed RCT has proven any therapy to be effective for perimenopausal VMS. Methods: To test progesterone for perimenopausal VMS, we ran a quadruple masked, randomized (1:1), placebo-controlled trial (2012-2016) with 28-day run-in and 84 days’ experimental phases. Our academic medical centre recruited locally/nationally for women ages 35-58 with cycle irregularity but menstruation within 12 months plus untreated, problematic VMS. Our primary, intent-to-treat outcome was participant-recorded daily VMS Score ([# night sweats x intensity]+[#daytime hot flushes x intensity]) days 56-84, adjusted for run-in VMS Score. Our secondary outcome was Women’s Perceived VMS Change (-5 to +5) on day 84. Findings: We randomized 189 women of mean (SD) age 49·9 (4·6) years to progesterone, 300 mg/bedtime [n=93], vs placebo [n=96]. The mean run-in VMS Score (n=189) was 12·2 (11·3). VMS Scores days 56-84 were not different by progesterone vs placebo (Rate Ratio [RR] 0·79 [95% CI 0·54, 1·15]; Rate Difference [RD] -1·51 [95% CI -3·97, 0·95]; P=0·222). RD 95% CI included -3, thus did not exclude a clinically important effect. Perceived VMS Change indicated progesterone significantly improved night sweats over placebo (-3 vs -2, P=0·023). No serious adverse events occurred. Interpretation: Progesterone-treated perimenopausal women perceived significantly improved night sweats. These results show trends toward clinically important VMS benefits from perimenopausal progesterone. Given the previously undocumented high perimenopausal VMS variability, a larger RCT of progesterone for perimenopause VMS is still needed. Trial Registered: ClinicalTrials.gov NCT0146469. Funding Statement: Funded by a grant from the Canadian Institutes for Health Research (#MOP106644). Extended enrollment was funded by an arms-length unrestricted grant to the Centre for Menstrual Cycle and Ovulation Research of the University of British Columbia from Besins Healthcare International. Declaration of Interests: None of the investigators, co-investigators or collaborators in this RCT has a financial or other conflict of interest with these data or other ethical conflicts. Ethics Approval Statement: The University of British Columbia Clinical Research Ethics Board approved this protocol and its amendments.

Research paper thumbnail of The impact of pre‐eclampsia definitions on the identification of adverse outcome risk in hypertensive pregnancy – analyses from the CHIPS trial (Control of Hypertension in Pregnancy Study)

BJOG: An International Journal of Obstetrics & Gynaecology, 2021

ObjectiveTo examine the association between pre‐eclampsia definition and pregnancy outcome.Design... more ObjectiveTo examine the association between pre‐eclampsia definition and pregnancy outcome.DesignSecondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data.SettingInternational multicentre randomised controlled trial (RCT).PopulationIn all, 987 women with non‐severe non‐proteinuric pregnancy hypertension.MethodsWe evaluated the association between pre‐eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control.Main outcome measuresMain CHIPS trial outcomes: primary (perinatal loss or high‐level neonatal care for >48 hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, delivery at <34 or <37 weeks, and maternal hospitalisation before birth.ResultsOf 979/987 women with informative data, 280 (28.6%) progressed to pre‐eclampsia defined restrictively by new proteinuria, and 471 (48.1%) to pre‐eclampsia defined broadly as proteinuria or one/more...

Research paper thumbnail of Sustained Dysregulation of the Plasma Renin-angiotensin System in Acute COVID-19

SARS-CoV-2 enters cells by binding to angiotensin-converting enzyme 2 (ACE2), and COVID-19 infect... more SARS-CoV-2 enters cells by binding to angiotensin-converting enzyme 2 (ACE2), and COVID-19 infection may therefore induce changes in the renin-angiotensin system (RAS). To determine the effects of COVID-19 on plasma RAS components, we measured plasma ACE, ACE2, and angiotensins I, (1-7), and II in 46 adults with COVID-19 at hospital admission and on days 2, 4, 7 and 14, compared to 50 blood donors (controls). We compared survivors vs. non-survivors, males vs. females, ventilated vs. not ventilated, and angiotensin receptor blocker (ARB) and angiotensin-converting enzyme (ACE) inhibitor-exposed vs. not exposed. At admission, COVID-19 patients had higher plasma levels of ACE (p=0.012), ACE2 (p=0.001) and angiotensin-(1-7) (p<0.001) than controls. Plasma ACE and ACE2 remained elevated for 14 days in COVID-19 patients, while plasma angiotensin-(1-7) decreased after 7 days. In adjusted analyses, plasma ACE was higher in males vs. females (p=0.042), and plasma angiotensin I was signifi...

Research paper thumbnail of Elevated Blood Mitochondrial DNA in Early Life Among Uninfected Children Exposed to Human Immunodeficiency Virus and Combination Antiretroviral Therapy in utero

The Journal of Infectious Diseases, 2020

BackgroundCombination antiretroviral therapy (cART) during pregnancy prevents vertical transmissi... more BackgroundCombination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life.MethodsWhole-blood mtDNA content at birth and in early life (age 0–3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated.ResultsAt birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged dur...

Research paper thumbnail of Congenital anomalies following antenatal exposure to dolutegravir: a Canadian surveillance study

BJOG: An International Journal of Obstetrics & Gynaecology, 2019

ObjectiveDolutegravir is recommended worldwide as a first‐line antiretroviral therapy (ART) for i... more ObjectiveDolutegravir is recommended worldwide as a first‐line antiretroviral therapy (ART) for individuals living with HIV. A recent study reported increased rates of neural tube defects in infants of dolutegravir‐treated women. This study examined rates of congenital anomalies in infants born to women living with HIV (WLWH) in Canada.DesignThe Canadian Perinatal HIV Surveillance Programme captures surveillance data on pregnant WLWH and their babies and was analysed to examine the incidence of congenital anomalies.SettingPaediatric HIV clinics.PopulationLive‐born infants born in Canada to WLWH between 2007 and 2017.MethodsData on mother–infant pairs, including maternal ART use at conception and during pregnancy, are collected by participating sites.Main outcome measuresCongenital anomalies.ResultsOf the 2423 WLWH, 85 (3.5%, 95% CI 2.85–4.36%) had non‐chromosomal congenital anomalies. There was no evidence of a significant difference in rates of congenital anomalies between women wh...

Research paper thumbnail of Oral cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028—study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune activation

BMJ Open, 2019

IntroductionDespite antiretroviral therapy (ART), people living with HIV have higher rates of non... more IntroductionDespite antiretroviral therapy (ART), people living with HIV have higher rates of non-infectious chronic diseases. These conditions are driven by relatively high levels of inflammation persisting on ART compared with uninfected individuals. Chronic inflammation also contributes to HIV persistence during ART. Cannabis when taken orally may represent a way to reduce inflammation and strengthen immune responses. Before planning large interventional studies, it is important to ensure that cannabis taken orally is safe and well tolerated in people living with HIV. We propose to conduct a pilot randomised trial to examine the safety and tolerability of cannabis oils containing tetrahydrocannabinol (THC) and cannabidiol (CBD) consumed orally in people living with HIV. We will also measure inflammatory markers, markers of HIV persistence in peripheral blood cells and changes in the gastrointestinal microbiome.Methods and analysisTwenty-six people living with HIV having undetecta...

Research paper thumbnail of 1614High Rates of Preterm Birth and Small for Gestational Age in a Cohort of HIV Infected Women in Canada: Role of Ritonavir Boosted Regimens?

Open Forum Infectious Diseases, 2014

Research paper thumbnail of O18.5 Examining hpv prevalence and uptake of cervical cancer screening among hiv positive and negative women participating in a pilot rct in uganda comparing self-collection based hpv testing to via

Sexually Transmitted Infections, 2015