Initiations of safer supply hydromorphone increased during the COVID-19 pandemic in Ontario: An interrupted time series analysis.

AIMS: Calls to prescribe safer supply hydromorphone (SSHM) as an alternative to the toxic drug supply increased during the COVID-19 pandemic but it is unknown whether prescribing behaviour was altered. We aimed to evaluate how the number of new SSHM dispensations changed during the pandemic in Ontario. METHODS: We conducted a retrospective interrupted time-series analysis using provincial administrative databases. We counted new SSHM dispensations in successive 28-day periods from March 22, 2016 to August 30, 2021. We used segmented Poisson regression methods to test for both a change in level and trend of new dispensations before and after March 17, 2020, the date Ontario's pandemic-related emergency was declared. We adjusted the models to account for seasonality and assessed for over-dispersion and residual autocorrelation. We used counterfactual analysis methods to estimate the number of new dispensations attributable to the pandemic. RESULTS: We identified 1489 new SSHM dispensations during the study period (434 [mean of 8 per 28-day period] before and 1055 [mean of 56 per 28-day period] during the pandemic). Median age of individuals initiating SSHM was 40 (interquartile interval 33-48) with 61.7% (N = 919) male sex. Before the pandemic, there was a small trend of increased prescribing (incidence rate ratio [IRR] per period 1.002; 95% confidence interval [95CI] 1.001-1.002; p<0.001), with a change in level (immediate increase) at the pandemic date (relative increase in IRR 1.674; 95CI 1.206-2.322; p = 0.002). The trend during the pandemic was not statistically significant (relative increase in IRR 1.000; 95CI 1.000-1.001; p = 0.251). We estimated 511 (95CI 327-695) new dispensations would not have occurred without the pandemic. CONCLUSION: The pandemic led to an abrupt increase in SSHM prescribing in Ontario, although the rate of increase was similar before and during the pandemic. The absolute number of individuals who accessed SSHM remained low throughout the pandemic.

COVID-19 vaccine antibody responses in community-dwelling adults to 48 weeks post primary vaccine series.

We report a decentralized prospective cohort study of self-reported adverse events and antibody responses to COVID vaccines derived from dried blood spots. Data are presented for 911 older (aged >70 years) and 375 younger (30-50 years) recruits to 48 weeks after the primary vaccine series. After a single vaccine, 83% younger and 45% older participants had overall seropositivity (p < 0.0001) increasing to 100/98% with the second dose, respectively (p = 0.084). A cancer diagnosis (p = 0.009), no mRNA-1273 vaccine doses (p <0 .0001), and older age (p <0 .0001) predicted lower responses. Antibody levels declined in both cohorts at 12 and 24 weeks increasing with booster doses. At 48 weeks, for participants with 3 vaccine doses, the median antibody levels were higher in the older cohort (p = 0.04) with any dose of mRNA-1273 (p <0 .0001) and with COVID infection (p <0 .001). The vaccines were well tolerated. Breakthrough COVID infections were uncommon (16% older cohort, 29% younger cohort; p < 0.0001) and mild.

Evaluation of the gap in delivery of opioid agonist therapy among individuals with opioid-related health problems: a population-based retrospective cohort study.

AIMS: Although opioid-related harms have reached new heights across North America, the size of the gap in opioid agonist therapy (OAT) delivery for opioid-related health problems is unknown in most jurisdictions. This study sought to characterize the gap in OAT treatment using a cascade of care framework, and determine factors associated with engagement and retention in treatment. DESIGN: A population-based retrospective cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Individuals who sought medical care for opioid-related health problems or died from an opioid-related cause between 2005 and 2019. MEASUREMENTS: Monthly treatment status for buprenorphine/naloxone or methadone OAT between 2013 and 2019 (i.e. 'off OAT', 'retained on OAT < 6 months', 'retained on OAT ≥ 6 months'). FINDINGS: Of 122 811 individuals in the cohort, 97 516 (79.4%) received OAT at least once during the study period. There was decreasing 6-month treatment retention over time. Model results indicated that males had higher odds of being on OAT each month [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.23-1.28] but lower odds of OAT retention (OR = 0.90, 95% CI = 0.88-0.92), while the reverse was observed for older individuals (monthly: OR = 0.76 per 10-year increase, 95% CI = 0.76-0.77; retention: OR = 1.36 per 10-year increase, 95% CI = 1.34-1.38) and individuals with higher neighbourhood income (e.g. highest income quintile, monthly: OR = 0.79, 95% CI = 0.77-0.82; highest income quintile, retention: OR = 1.15, 95% CI = 1.11-1.20). Individuals residing in rural areas and with a history of mental health diagnoses had poorer outcomes overall, including lower odds of being on OAT each month (rural: OR = 0.75, 95% CI = 0.73-0.78; mental health: OR = 0.89, 95% CI = 0.87-0.92) and OAT retention (rural: OR = 0.79, 95% CI = 0.77-0.82; mental health: OR = 0.81, 95% CI = 0.78-0.83), as well as higher risk of starting/stopping OAT [rural, starting OAT: hazard ratio (HR) = 1.07, 95% CI = 1.05-1.10; mental health, starting OAT: HR = 1.20, 95% CI: 1.18-1.23; rural, stopping OAT: HR = 1.24, 95% CI: = 1.22-1.26; mental health, stopping OAT: HR = 1.11, 95% CI = 1.09-1.13]. Individuals with a history of mental health diagnoses also had a higher risk of death, regardless of OAT status (off OAT death: HR = 1.49, 95% CI = 1.33-1.66; on OAT death: HR = 1.20, 95% CI = 1.09-1.31). CONCLUSIONS: Factors influencing engagement and declining retention in treatment with opioid agonist therapy in Ontario's health system include age, sex and neighbourhood income, as well as mental health diagnoses or residing in rural regions.

Influence of previous experience with and beliefs regarding anal cancer screening on willingness to be screened among men living with HIV.

BACKGROUND: Implementation of anal cancer screening requires the procedure to be acceptable to the target population. Our objective was to assess the beliefs of men living with HIV regarding anal cancer screening and identify factors associated with their willingness to participate in screening. METHODS: We developed a cross-sectional questionnaire using the Theory of Planned Behavior to examine beliefs regarding prevention of human papillomavirus (HPV)-related diseases, administered to men living with HIV in 2016-2017 in a multi-site HIV clinical cohort. Correspondence analysis was used to examine the interrelationships between men's beliefs and willingness to undergo anal cancer screening. We used multivariable proportional odds models to identify factors associated with increasing willingness. Results were reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Among 1677 male participants, the vast majority (90%) would be willing to undergo screening by "anal Pap test"; willingness clustered with positive beliefs (e.g. confident they can get screened; disagree that they will feel pain) in the correspondence analysis. Higher self-perceived risk for anal cancer and positive beliefs regarding screening were associated with higher willingness to be screened. Gay, bisexual and other men who have sex with men had higher willingness (aOR = 1.62; 95% CI: 1.15, 2.29) than heterosexual men. Racialized men reported lower willingness (aOR = 0.68; 95% CI: 0.54, 0.89) than white men. CONCLUSIONS: Men generally had positive beliefs and were willing to undergo screening, though there were differences by sexual orientation and racial identity. Tailored community-led initiatives could focus on men's understanding of their risk and expectations of anal cancer screening to facilitate participation.

Low human papillomavirus vaccine uptake among women engaged in HIV care in Ontario, Canada.

Women living with HIV are at higher risk for human papillomavirus (HPV)-related dysplasia and cancers and thus are prioritized for HPV vaccination. We measured HPV vaccine uptake among women engaged in HIV care in Ontario, Canada, and identified socio-demographic, behavioural, and clinical characteristics associated with HPV vaccination. During annual interviews from 2017 to 2020, women participating in a multi-site, clinical HIV cohort responded to a cross-sectional survey on HPV vaccine knowledge and receipt. We used logistic regression to derive age-adjusted odds ratios and 95% confidence intervals (CI) for factors associated with self-reported vaccine initiation (≥1 dose) or series completion (3 doses). Among 591 women (median age = 48 years; interquartile range = 40-56 years), 13.2% (95%CI = 10.5-15.9%) had received ≥1 dose. Of those vaccinated, 64.6% had received 3 doses. Vaccine initiation (≥1 dose) was significantly higher among women aged 20-29 years at 31.0% but fell to 13.9% in those aged 30-49 years and < 10% in those aged ≥50 years. After age adjustment, vaccine initiation was significantly associated with being employed (vs. unemployed but seeking work), income $40,000-$59,999 (vs. <$20,000), being married/common-law (vs. single), living with children, immigrating to Canada >5 years ago (vs. immigrating ≤5 years ago), never smoking (vs. currently smoking), and being in HIV care longer (per 10 years). Similar factors were identified for series completion (3 doses). HPV vaccine uptake remains low among women living with HIV in our cohort despite regular engagement in care. Recommendations for improving uptake include education of healthcare providers, targeted community outreach, and public funding of HPV vaccination.

Efficiency in the Endoscopy Unit: Can We 'Turn Around' Room Turnover? An Observational Quality Improvement Study.

Background: Endoscopy units are being challenged to provide timely and quality care, despite limited resources and an ever-growing patient population. Decreasing procedure time is unlikely to create sufficient time savings and may compromise quality. Non-procedural factors, such as room turnover, are important contributors to efficiency and represent an ideal target for quality improvement efforts. Aims: The objective of this quality improvement study was to identify practices that will improve endoscopy unit efficiency at our centre. The specific aims were to (a) understand practices at local hospitals that contribute to room turnover efficiency and (b) examine the magnitude and sources of variation in room turnover efficiency across endoscopists and nurses at our centre. Methods: Interviews were conducted with team leads at five local hospitals. Routinely collected data from our centre were analyzed to understand the magnitude and variation in efficiency by provider and reasons for delays. Non-procedure time defined as 'patient 1 scope out' to 'patient 2 scope in' was our primary measure of efficiency. Results: Over the 12-month period, 750 outpatient procedures met inclusion criteria. Median non-procedure time was 19 min (interquartile range: 16-22 min). The variation attributable to endoscopists was 14.7% compared to 80.4% for unmeasured factors. Conclusions: The variation that remains unexplained by our model suggests that unmeasured factors play a substantial role in endoscopy unit efficiency and that our current endoscopy records are not capturing important contributors to efficiency. The next phase will involve focus groups and direct observation with the goal of identifying these unmeasured factors.

Routinized Syphilis Screening Among Men Living With Human Immunodeficiency Virus: A Stepped Wedge Cluster Randomized Controlled Trial.

BACKGROUND: We implemented an opt-out clinic-based intervention pairing syphilis tests with routine human immunodeficiency virus (HIV) viral load testing. The primary objective was to determine the degree to which this intervention increased the detection of early syphilis. METHODS: The Enhanced Syphilis Screening Among HIV-Positive Men (ESSAHM) Trial was a stepped wedge cluster-randomized controlled trial involving 4 urban HIV clinics in Ontario, Canada, from 2015 to 2017. The population was HIV-positive adult males. The intervention was standing orders for syphilis serological testing with viral loads, and control was usual practice. We obtained test results via linkage with the centralized provincial laboratory and defined cases using a standardized clinical worksheet and medical record review. We employed a generalized linear mixed model with a logit link to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of the intervention. RESULTS: A total of 3895 men were followed over 7471 person-years. The mean number of syphilis tests increased from 0.53 to 2.02 tests per person per year. There were 217 new diagnoses of syphilis (control, 81; intervention, 136), for which 147 (68%) were cases of early syphilis (control, 61 [75%]; intervention, 86 [63%]). The annualized proportion with newly detected early syphilis increased from 0.009 to 0.032 with implementation of the intervention; the corresponding time-adjusted OR was 1.25 (95% CI, .71-2.20). CONCLUSIONS: The implementation of standing orders for syphilis testing with HIV viral loads was feasible and increased testing, yet produced less-than-expected increases in case detection compared to past uncontrolled pre-post trials. CLINICAL TRIALS REGISTRATION: NCT02019043.

Low human papillomavirus (HPV) vaccine uptake among men living with human immunodeficiency virus (HIV): Cross-sectional findings from a clinical cohort.

Men living with human immunodeficiency virus (HIV) are internationally recognized as a priority population for human papillomavirus (HPV) vaccination. Our objective was to explore HPV vaccine uptake among men living with HIV in Ontario, Canada, and investigate differences between vaccinated and unvaccinated men. We used data from a cross-sectional questionnaire administered between 2016 and 2017 among men living with HIV and participating in the Ontario HIV Treatment Network Cohort Study. We calculated the proportion vaccinated against HPV, described vaccination experiences, and HPV vaccine knowledge, and calculated differences in characteristics between vaccinated and unvaccinated men. Among 1651 men (mean age = 51 years, 72% identified as gay), 7% were vaccinated (95% confidence interval[CI] 5.5-7.9%); 85% received their first dose at a primary care or HIV clinic. Among unvaccinated men, 40% were unaware of the HPV vaccine, 65% reported low perceived risk for HPV, and 8% discussed HPV vaccination with a physician. Compared to unvaccinated men, vaccinated men were younger, most identified as gay, had a higher education/income, reported a higher number of recent sex partners, and had a history of bacterial sexually transmitted infections (STIs), HPV, anogenital warts, and/or anal cancer. Our findings reveal that few men living with HIV were vaccinated against HPV. This may be influenced by low HPV awareness, prohibitive cost, and lack of physician recommendation. Several men reporting lower socio-economic status, older men, and heterosexual, bisexual, and other men who have sex with men were missed for vaccination. Primary care and HIV clinics may be ideal locations to increase uptake.

Low human papillomavirus (HPV) knowledge related to low risk perception among men living with HIV: Implications for HPV-associated disease prevention.

Human papillomavirus (HPV)-associated anal cancer is orders of magnitude higher among men living with HIV than the general male population. Our objective was to examine factors associated with HPV awareness and self-perceived risk for HPV-associated anal cancer among men living with HIV, which may influence uptake of cancer prevention strategies. A cross-sectional questionnaire on HPV was administered from 2016 to 2017 to 1677 men in a multisite, HIV clinical cohort in Ontario, Canada. We used logistic regression and proportional odds models to identify factors associated with being familiar with HPV and increasing self-perceived risk for anal cancer, respectively. We used correspondence analysis to examine associations of specific HPV-related knowledge with self-perceived risk. Only 52% were familiar with HPV, and 72% felt they had no or low risk for anal cancer. Familiarity with HPV was more common among men who have sex with men than heterosexual men (58% vs. 21%). Older men were less likely to be familiar with HPV (adjusted odds ratio [aOR] per 10 years = 0.77; 95% confidence interval [CI]: 0.69, 0.85). Familiarity with HPV was associated with increasing self-perceived risk (aOR = 2.39; 95% CI: 1.87, 3.04). After accounting for differences in HPV awareness and sexual orientation, racialized men had lower self-perceived risk (aOR = 0.68; 95% CI: 0.52, 0.88). In the correspondence analysis, risk-focused HPV-related knowledge (e.g., knowing smoking increases risk) was associated with highest risk perception. Efforts are needed to improve HPV-related health literacy in this population. Our findings suggest specific HPV-related knowledge may differentially influence self-perceived risk for anal cancer.

Examining the association between stress and antiretroviral therapy adherence among women living with HIV in Toronto, Ontario.

BACKGROUND: We aimed to identify the association between stress and antiretroviral therapy (ART) adherence among women in HIV care in Toronto, Ontario participating in the Ontario HIV Treatment Network Cohort Study (OCS) between 2007 and 2012. MATERIALS AND METHODS: We conducted cross-sectional analyses with women on ART completing the AIDS Clinical Trial Group (ACTG) Adherence Questionnaire. Data closest to, or at the last completed interview, were collected from medical charts, through record linkage with Public Health Ontario Laboratories, and from a standardized self-reported questionnaire comprised of socio-demographic and psycho-socio-behavioral measures (Center for Epidemiologic Studies Depression Scale (CES-D), Alcohol Use Disorders Identification Test (AUDIT)), and stress measures (National Population Health Survey). Logistic regression was used to quantify associations with optimal adherence (≥95% adherence defined as missing ≤ one dose of ART in the past 4 weeks). RESULTS: Among 307 women, 65.5% had optimal adherence. Women with suboptimal compared to optimal adherence had higher median total stress scores (6.0 [interquartile range (IQR): 3.0-8.1] vs. 4.1 [IQR: 2.0-7.1], p = 0.001), CES-D scores (16 [IQR: 6-28] vs. 12 [IQR: 3-22], p = 0.008) and reports of hazardous and harmful alcohol use (31.1% vs. 17.9%, p = 0.008). In our multivariable model, we found an increased likelihood of optimal adherence with the absence of hazardous and harmful alcohol use (Adjusted Odds Ratio (AOR)=2.20, 95% confidence interval (CI): 1.12-4.32) and a decreased likelihood of optimal adherence with more self-reported stress (AOR = 0.56, 95% CI: 0.33-0.94). CONCLUSIONS: Interventions supporting optimal ART adherence should address stress and include strategies to reduce or eliminate hazardous and harmful alcohol use for women living with HIV.

Prevalent and persistent oncogenic HPV types in a cohort of women living with HIV prior to HPV vaccination.

OBJECTIVE: To describe prevalent and persistent oncogenic human papillomavirus (HPV) types detected in women living with HIV (WLWH) in Canada, including women with cervical dyskaryosis, and to determine predictors of type-specific HPV persistence. METHODS: Women and girls living with HIV, recruited from 14 sites of HIV care across Canada, were included in a sub-analysis of a prospective vaccine immunogenicity cohort study (two HPV DNA results, at least one cervical cytology result pre-vaccination). Demographic and clinical data were collected alongside cervical samples for cytology and HPV DNA typing between November 25, 2008, and May 19, 2015. RESULTS: Pre-vaccination, HPV16 and HPV52 were the most prevalent oncogenic HPV types. Of the 252 women and girls who met the eligibility criteria, 45% were infected with at least one oncogenic HPV type and one-third of participants had a persistent oncogenic infection. HPV16, 45, and 52 were the most frequently persistent types. Seventeen percent of women had persistent infections with oncogenic HPV types not within currently available vaccines (HPV35/39/51/56/59/68/82). Lower CD4 count significantly predicted HPV persistence (P=0.024). Cervical cytology results were normal for 82.9% of participants, atypical squamous cells of undetermined significance for 2.4%, low-grade squamous intraepithelial lesions for 11.5%, and high-grade squamous intraepithelial lesions for 2.8%. CONCLUSION: Unvaccinated WLWH were infected with a wide range of oncogenic HPV types. The findings highlighted the importance of optimal treatment of HIV and continued cervical cancer screening as key steps toward the global elimination of cervical cancer.

Impact of quadrivalent HPV vaccine dose spacing on immunologic response in women living with HIV.

HPV vaccination schedules have changed as evidence has supported reduced dosing and extended intervals. Women living with HIV (WLWH) represent an important population with no data on alternative dosing. Girls and WLWH received quadrivalent HPV (qHPV) vaccine in a pan-Canadian study of immunogenicity and efficacy. Serology was performed at months 0/2/7/12/18/24. Medical and sexual history was collected throughout. Linear regression was used to determine if spacing of doses was associated with peak antibody titer. Multivariable analyses demonstrated significant relationships between peak antibody titer and time to blood draw post last vaccine dose, naivety to the relevant HPV type, and HIV viral load for all qHPV types. There was a significant relationship between peak HPV16/18 antibody titer and age. Taking age, time to serology, CD4 cell count, CD4 nadir, HIV viral load, and HPV naivety into account, spacing of the three qHPV vaccine doses did not significantly impact peak antibody titers.

Incidence of chronic obstructive pulmonary disease in people with HIV in Ontario, 1996-2015: a retrospective population-based cohort study.

BACKGROUND: Because of high smoking rates and HIV-related factors, people with HIV may be at high risk for chronic obstructive pulmonary disease (COPD); however, population-based estimates of the incidence of COPD among people with HIV are lacking, particularly for women. We compared the incidence of COPD among Ontario adults aged 35 years or more with and without HIV between Jan. 1, 1996, and Dec. 31, 2015. METHODS: We conducted a population-based study using Ontario's health administrative databases. We compared the incidence of COPD between people with and without HIV using standardized incidence ratios and generalized estimating equations with a log link function. RESULTS: We identified 1849 people with HIV and 1 168 727 HIV-negative people who were newly diagnosed with COPD between 1996 and 2015. People with HIV were younger than HIV-negative people (mean age 49.7 [standard deviation 10.4] yr v. 62.2 [standard deviation 14.8] yr; standardized difference 0.98). Rates of COPD were higher among people with HIV than among HIV-negative people (10.4 v. 9.0 cases per 1000 person-years; standardized incidence ratio 1.16, 95% confidence interval [CI] 1.10 to 1.21; adjusted rate ratio 1.34, 95% CI 1.27 to 1.41). In sex-stratified analyses, rates of COPD were higher among men with HIV (adjusted rate ratio 1.32, 95% CI 1.24 to 1.40) and women with HIV (adjusted rate ratio 1.54, 95% CI 1.37 to 1.72) than among men and women without HIV. In a sensitivity analysis, smoking explained observed differences in COPD incidence. INTERPRETATION: People with HIV had higher rates of incident COPD than HIV-negative people. This may reflect the disproportionately higher prevalence of smoking among the former.

Racial Disparities in Anal Cancer Screening Among Men Living With HIV: Findings From a Clinical Cohort Study.

BACKGROUND: Our objective was to quantify the extent of anal cancer screening among men receiving HIV specialty care in Ontario, Canada, and evaluate factors associated with screening. SETTING: Cross-sectional questionnaire within a multisite clinical HIV cohort. METHODS: A questionnaire assessing knowledge and experience with human papillomavirus-associated diseases and their prevention was administered in 2016-2017 to 1677 men in the Ontario HIV Treatment Network Cohort Study. We used logistic regression to identify factors associated with having discussed screening with a health care provider and self-reported receipt of screening [digital anal rectal examinations (DARE); anal cytology or anoscopy]. Results reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: Forty percent of men reported ever having had anal cytology/anoscopy, and 70% had ever had DARE. After accounting for differences in age, sexual orientation, years since HIV diagnosis, previous diagnosis with AIDS, knowing someone with human papillomavirus-associated cancer, comfort discussing anal health, education, and income, the proportion screened differed by self-identified race. Compared with white men, Asian men were less likely to have discussed screening with a health care provider (aOR = 0.48; 95% CI: 0.29 to 0.80) or to have been screened by DARE (aOR = 0.27; 95% CI: 0.17 to 0.44) or anal cytology/anoscopy (aOR = 0.51; 95% CI: 0.31 to 0.83), and African, Caribbean, or black men (aOR = 0.47; 95% CI: 0.31 to 0.70) were less likely to have had DARE. Results were consistent when restricting the analyses to gay, bisexual, and other men who have sex with men. CONCLUSION: Our findings highlight the potential for disparities in anal cancer screening that need to be considered when developing guidelines and screening programs to reduce the burden of anal cancer among men living with HIV and ensure health equity.

Brief Report: Persistence of Non-Vaccine Oncogenic HPV Genotypes in Quadrivalent HPV-Vaccinated Women Living With HIV.

BACKGROUND: Human papillomavirus (HPV) vaccines have promising safety and immunogenicity data in women living with HIV (WLWH). However, it is critical to understand the residual burden of oncogenic HPV within WLWH to inform postvaccination cervical screening needs. We assessed rates of persistent infection with nonquadrivalent HPV (qHPV) oncogenic types in a cohort of qHPV-vaccinated WLWH. SETTING: Multicentre, longitudinal cohort across Canada. METHODS: WLWH were scheduled to receive 3 doses of qHPV vaccine. Participants provided health data and HPV DNA samples. Persistent cases of HPV were defined as new HPV in samples from ≥2 consecutive visits or as HPV present in the last sample. HPV31/33/35/39/45/51/52/56/58/59/68/82 were considered to have oncogenic potential. Median follow-up time was 4 years after initial vaccine dose. RESULTS: A total of 284 participants were eligible for this analysis with 1205 person-years (PY) of follow-up (≥1 dose of vaccine, ≥1 HPV DNA result after vaccination). The highest incidence of persistent infection was with HPV51 (1.38/100 PY), followed by HPV52 (1.18/100 PY), and HPV39 (1.06/100 PY). The incidence of persistent infection with pooled HPV types added in the nonavalent vaccine (HPV31/33/45/52/58) was lower than the incidence of persistent oncogenic HPV types not contained within available vaccines (HPV35/39/51/56/59/68) (2.4/100 PY versus 3.6/100 PY, respectively). CONCLUSIONS: qHPV-vaccinated WLWH continue to face a burden of persistent oncogenic HPV infection. Although the nonavalent vaccine could alleviate some of this burden, 2 of the top 3 persistent oncogenic HPVs in this cohort are not contained within any available vaccine. This highlights the need for ongoing cervical screening in HPV-vaccinated WLWH.

Comparison of guidelines for HIV viral load monitoring among pregnant and breastfeeding women in sub-Saharan Africa.

BACKGROUND: Intensified viral load monitoring for pregnant and breastfeeding women has been proposed to help address concerns around antiretroviral therapy (ART) adherence, viraemia and transmission risk, but there have been no systematic evaluations of existing policies. METHODS: We used an individual Monte Carlo simulation to describe longitudinal ART adherence and viral load from conception until 2 years' postpartum. We applied national and international guidelines for viral load monitoring to the simulated data. We compared guidelines on the percentage of women receiving viral load monitoring and the percentage of women monitored at the time of elevated viral load. RESULTS: Coverage of viral load monitoring in pregnancy and breastfeeding varied markedly, with between 14% and 100% of women monitored antenatally and 38-98% monitored during breastfeeding. Specific recommendations for testing at either a fixed gestation or a short, fixed period after ART initiation achieved more than 95% testing in pregnancy but this was much lower (14-83%) among guidelines with no special stipulations. By the end of breastfeeding, only a small proportion of simulated episodes of elevated viral load more than 1000 copies/ml were successfully detected by monitoring (range, 20-50%). DISCUSSION: Although further research is needed to understand optimal viral load frequency and timing in this population, these results suggest that current policies yield suboptimal detection of elevated viral load in pregnant and breastfeeding women.

Inflammatory biomarker levels over 48 weeks with dual vs triple lopinavir/ritonavir-based therapy: Substudy of a randomized trial.

BACKGROUND: Inflammation has been associated with increased morbidity and mortality in HIV-positive patients. We compared inflammatory biomarkers with dual therapy using lopinavir/ritonavir plus lamivudine (LPV/r+3TC) versus triple therapy using LPV/r plus two nucleoside reverse transcriptase inhibitors (LPV/r+2NRTIs) in treatment-naïve HIV-positive adults. METHODS: This was a substudy among Argentinian participants in the randomized trial GARDEL. We measured hsCRP, IL-6, MCP-1, TNF, D-dimer and sCD14 from plasma collected at baseline, week 24 and week 48. Generalized estimating equations with an identity/logit link were used to model the average impact of dual versus triple therapy on each biomarker over time, controlling for baseline levels. Additional models estimated the average effect of virologic suppression on biomarker levels over time, adjusting for age, sex, and baseline CD4 count. RESULTS: Of 191 trial participants enrolled in Argentina, 172 had baseline and follow-up measurements and were included. Median (IQR) age was 35.5 (28.5, 45) years and CD4 cell count was 310 (219, 414) cells/mm3. Dual therapy was not associated with significantly different biomarker levels over 48 weeks relative to triple therapy. Virologic suppression was associated with statistically significant decreases in MCP-1, TNF and D-dimer levels and an unexpected increase in sCD14 levels. No change was observed in hsCRP or the proportion of participants with undetectable IL-6 levels. CONCLUSIONS: In addition to having virologic non-inferiority, LPV/r+3TC dual therapy is generally associated with similar inflammatory biomarker levels over 48 weeks compared to LPV/r+2NRTIs triple therapy in treatment-naïve adults. Further study of dual treatment regimens is warranted.

Tenofovir and emtricitabine resistance among antiretroviral-naive patients in the Canadian Observational Cohort Collaboration: implications for PrEP.

BACKGROUND: The real-world effectiveness of pre-exposure prophylaxis (PrEP) may be influenced by circulating HIV strains resistant to either tenofovir or emtricitabine. Yet, few studies have examined rates of resistance to these drugs in clinical settings. METHODS: We conducted a retrospective cohort study of antiretroviral-naive participants in the Canadian Observational Cohort collaboration who initiated antiretroviral therapy between 2006 and 2014. In separate analyses, we determined the prevalence of pretherapy resistance and cumulative incidence of follow-up resistance to tenofovir and emtricitabine. We used multivariable proportional hazards models to examine associations between baseline variables and the development of resistance. RESULTS: We studied 6,622 antiretroviral-naive participants initiating therapy, of whom 5,428 (82.0%) had a baseline resistance test. Baseline resistance to tenofovir and emtricitabine was observed in 83 (1.5%) and 21 (0.4%) patients, respectively. Among patients without baseline resistance, the cumulative incidence of resistance to tenofovir and emtricitabine 5 years following treatment initiation was 0.0070 (95% CI 0.0046, 0.0095) and 0.033 (95% CI 0.028, 0.038), respectively. Following multivariable analysis, a baseline viral load ≥100,000 copies/ml was associated with emergence of tenofovir (hazard ratio [HR] 2.88; 95% CI 1.35, 6.15) and emtricitabine (HR 2.27; 95% CI 1.64, 3.15) resistance. Initiating an integrase inhibitor-based regimen and CD4+ T-cell count below 200 cells/mm3 were also associated with resistance to each drug. CONCLUSIONS: We observed a low prevalence of baseline resistance and a low incidence of emergence of resistance to tenofovir and emtricitabine among antiretroviral-naive patients in routine clinical care.

Brief Report: Syphilis Coinfection Is Not Associated With an Increased Risk of Virologic Failure Among HIV-Positive Men Who Have Sex With Men on Antiretroviral Therapy.

BACKGROUND: Incidence of syphilis continues to increase among HIV-positive men who have sex with men (MSM) in Ontario. Our objective was to determine the effect of acute syphilis on virologic failure (VF) among virally suppressed HIV-positive MSM taking antiretroviral therapy (ART) and determine if the relationship is confounded by drug use. SETTING: The OHTN Cohort Study is a voluntary cohort of people receiving HIV care in Ontario. Syphilis and viral load (VL) data were retrieved via linkage with the provincial laboratory. METHODS: Analyses included 2632 MSM from 2008 to 2015, on ART, with ≥1 questionnaire and 2 consecutive VL of <50 copies per milliliter 6 months apart. VF was defined as (1) VL of ≥1000 copies per milliliter or (2) 2 consecutive VLs of ≥200 copies per milliliter ≥1 month apart. We modeled acute syphilis as a time-varying covariate on VF using Poisson regression. Time-varying drug use was assessed for confounding using an iterative process where potential confounders were removed and then reintroduced into the model. Our model allowed for repeat observations using generalized estimating equations. RESULTS: VF incidence was 3.5 per 100 person-years [95% confidence interval (CI): 3.4 to 4.2]. The rate ratio for VF for acute syphilis was 1.5 (95% CI: 0.9 to 2.4) in the unadjusted model; 1.6 (95% CI: 1.0 to 2.4) in the model adjusted for age, education, region, and income; and 1.2 (95% CI: 0.7 to 1.9) in the final model with additional adjustment for drug use. CONCLUSIONS: Acute syphilis was not associated with VF among virologically suppressed MSM on ART. Consequently, ART may still reduce HIV transmission risk to sexual partners.