Clinical HIV outcome trajectories associated with a history of child protective service out-of-home care: Longitudinal cohort findings with women living with HIV in Canada.

OBJECTIVES: Knowledge gaps exist regarding the effects of experiencing child protective services (CPS) out-of-home care (e.g. foster homes) among women with HIV. We examined whether CPS out-of-home care was associated with HIV clinical outcome trajectories among women with HIV in a longitudinal cohort study in Ontario, British Columbia, and Quebec, Canada. METHODS: At three timepoints across 5 years (2013-2018), we examined self-reported current antiretroviral therapy (ART) use and viral load (VL) detectability (>50 copies/mL). We used latent class growth analysis (LCGA) to identify trajectories of ART use and VL outcomes across study waves. LCGA identifies subgroups (classes) with similar trajectories within the sample. We assessed whether HIV outcome trajectories could be predicted by CPS history. We then conducted a mediation analysis to test whether a mental health latent construct mediated the association between CPS history and detectable VL. RESULTS: Nearly one-fifth (n = 272; 19%) of participants (n = 1422; mean age 42.8 years) reported CPS out-of-home care. Most participants (89%) were in classes that consistently used ART and had an undetectable VL. Individuals with CPS out-of-home care histories were twice as likely to have a consistently detectable VL (ß = 0.72, p = 0.02); there were no differences in ART use trajectories. In mediation analyses, we found an indirect path from CPS history to a consistently detectable VL via baseline mental health status (ß = 0.02, 95% confidence interval 0.005-0.04, p = 0.02), with a significant odds ratio (1.12, z = 2.43, p = 0.02). CONCLUSION: Among women with HIV in Canada, experiencing childhood CPS out-of-home care was associated with a reduced likelihood of achieving viral suppression, via poorer mental health.

Experiences and resultant care gaps among women with HIV in Canada: concept mapping the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) findings.

OBJECTIVES: The community-based, longitudinal, Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) explored the experiences of women with HIV in Canada over the past decade. CHIWOS' high-impact publications document significant gaps in the provision of healthcare to women with HIV. We used concept mapping to analyse and present a summary of CHIWOS findings on women's experiences navigating these gaps. DESIGN: Concept mapping procedures were performed in two steps between June 2019 and March 2021. First, two reviewers (AY and PM) independently reviewed CHIWOS manuscripts and conference abstracts written before 1 August 2019 to identify main themes and generate individual concept maps. Next, the preliminary results were presented to national experts, including women with HIV, to consolidate findings into visuals summarising the experiences and care gaps of women with HIV in CHIWOS. SETTING: British Columbia, Ontario and Quebec, Canada. PARTICIPANTS: A total of 18 individual CHIWOS team members participated in this study including six lead investigators of CHIWOS and 12 community researchers. RESULTS: Overall, a total of 60 peer-reviewed manuscripts and conference abstracts met the inclusion criteria. Using concept mapping, themes were generated and structured through online meetings. In total, six composite concept maps were co-developed: quality of life, HIV care, psychosocial and mental health, sexual health, reproductive health, and trans women's health. Two summary diagrams were created encompassing the concept map themes, one for all women and one specific to trans women with HIV. Through our analysis, resilience, social support, positive healthy actions and women-centred HIV care were highlighted as strengths leading to well-being for women with HIV. CONCLUSIONS: Concept mapping resulted in a composite summary of 60 peer-reviewed CHIWOS publications. This activity allows for priority setting to optimise care and well-being for women with HIV.

Use of a carrageenan-based gel had no impact on anal HPVs 16 and 18 viral loads in gay, bisexual, and other men who have sex with men.

The Lubricant Investigation in Men to Inhibit Transmission of human papillomavirus (HPV) Infection randomized control trial in gay, bisexual, and other men who have sex with men (gbMSM) found that carrageenan use neither reduced acquisition of anal HPV infections nor influenced infection clearance. To investigate carrageenan's lack of protective effect, we compared the change in anal HPV16 and HPV18 viral loads following carrageenan use against placebo. We restricted our analysis to participants who completed the first four study visits and had a valid baseline sample (n = 161, 54 HIV-positive). Samples were tested for HPV detection using the linear array PCR assay. HPV16- and/or HPV18-positive samples were tested for viral load using real-time PCR. For participants who tested HPV16- (n = 29) or HPV18-positive (n = 10) at least once across visits 1-4, we compared the change in type-specific viral load between study arms using the Mann-Whitney U test. Although the median net change in HPV16 and HPV18 viral loads across visits 1-4 was higher in the treatment than placebo arm (HPV16: 0.68 vs. 0.18 copies/cell, p = 0.60; HPV18: 18.32 vs. 10.12 copies/cell, p = 0.52), these differences were not statistically significant. Results were similar by HIV status. Carrageenan use did not impact anal HPV16 or HPV18 viral loads, which may further explain its lack of protective effect in gbMSM.

Exploring pregnant individuals' counseling needs regarding urgent imaging to rule out pulmonary embolism.

Background: Computed tomography pulmonary angiogram and lung scintigraphy with ventilation/perfusion scan are needed to diagnose pulmonary embolism (PE) in pregnancy. Their associated ionizing radiation doses are considered safe in pregnancy. A standardized patient information tool may improve patient counseling and reduce testing hesitancy. Objectives: In this context, we sought to address 1) what patients want to know before undergoing these tests and 2) how they want the information to be provided to them. Methods: We used a qualitative descriptive methodology. We recruited pregnant participants at the McGill University Health Center in Montreal, Canada. Structured interviews explored information needs about PE and diagnostic imaging for PE. The interview transcripts' themes were analyzed with a hybrid deductive and inductive approach. Results: Of 21 individuals approached, 20 consented to participate. Four had been previously investigated for PE. Participants requested information about the risks associated with PE and radiation and their effects on maternal and fetal health. They preferred for radiation doses to be presented in comparison with known radiation thresholds for fetal harm. They suggested that a written tool should be developed using an accessible language. Participants also indicated that the tool would be integrated into their decision-making process, emphasizing a lower risk tolerance for their fetus than for themselves. Conclusion: This single-center group of pregnant patients wished to be informed about the risks of PE and radiation associated with imaging. A written tool could help put information into context and facilitate decision making. These new insights may be used to inform counseling.

Dissemination of the Women-Centred HIV Care Model: A Multimodal Process and Evaluation.

BACKGROUND: Using data from a national cohort study and focus groups, the Women-Centred HIV Care (WCHC) Model was developed to inform care delivery for women living with HIV. METHODS: Through an evidence-based, integrated knowledge translation approach, we developed 2 toolkits based on the WCHC Model for service providers and women living with HIV in English and French (Canada's national languages). To disseminate, we distributed printed advertising materials, hosted 3 national webinars and conducted 2 virtual capacity-building training series. RESULTS: A total of 315 individuals attended the webinars, and the average WCHC knowledge increased by 29% (SD 4.3%). In total, 131 service providers engaged in 22 virtual capacity-building training sessions with 21 clinical cases discussed. Learners self-reported increased confidence in 15/15 abilities, including the ability to provide WCHC. As of December 2023, the toolkits were downloaded 7766 times. CONCLUSIONS: We successfully developed WCHC toolkits and shared them with diverse clinical and community audiences through various dissemination methods.

A study on creating and sharing a toolkit for healthcare providers and women living with HIVWhy was the study done?:The research team created the Women-Centred HIV Care (WCHC) model to help healthcare providers deliver personalised and thorough care to women living with HIV in Canada. This study aimed to develop a practical toolkit based on the model. The goal was to share this toolkit with women and their providers in various ways to get feedback on its usefulness and to understand the best methods for sharing tools in the future.What did the researchers do?:Through an in-depth, collaborative process, English and French WCHC toolkits were developed by a large and diverse team of women and providers. Various methods including printed materials, national webinars and virtual trainings were used to share the toolkits across Canada. The team assessed the toolkit's reception by using surveys, focus groups and tracking toolkit downloads and webpage views.What did the researchers find?:The study found positive results, including a 29% increase in WCHC knowledge for 315 webinar participants and enhanced confidence in 15 abilities for 131 service providers during virtual training. The toolkits were downloaded 7766 times, indicating broad interest. Usability testing showed that the toolkits were easy to use and helpful. Attendees of the webinars and virtual trainings indicated they were likely to use the toolkit and recommend it to others.What do the findings mean?:Overall, the WCHC toolkits offer valuable guidance to women living with HIV and their providers. The study improved providers' knowledge and confidence in delivering WCHC, especially during the virtual training sessions that focused on applying this knowledge to real clinical cases. During months when the toolkit was shared through printed materials, webinars and virtual training, more people visited the toolkit webpage. The study highlighted the importance of involving those who will use healthcare tools from the beginning and using many ways to share these tools to reach more people.

Impact of social determinants of health on time to antiretroviral therapy initiation and HIV viral undetectability for migrants enrolled in a multidisciplinary HIV clinic with rapid, free, and onsite B/F/TAF: 'The ASAP study'.

OBJECTIVE: Multidisciplinary care with free, rapid, and on-site bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) dispensation may improve health outcomes among migrants living with HIV. However, models for rapid B/F/TAF initiation are not well studied among migrants living with HIV, and an understanding of how social determinants of health (SDH) may affect HIV-related health outcomes for migrants enrolled in such care models is limited. METHODS: Within a 96-week pilot feasibility prospective cohort study at a multidisciplinary HIV clinic, participants received free B/F/TAF rapidly after care linkage. The effects of SDH (i.e., birth region, sexual orientation, living status, education, employment, French proficiency, health coverage, use of a public health facility outside our clinic for free blood tests, and time in Canada) and other covariates (i.e., age, sex) on median time to antiretroviral therapy (ART) initiation and HIV viral undetectability from care linkage were calculated via survival analyses. RESULTS: Thirty-five migrants were enrolled in this study. Median time to ART initiation and HIV undetectability was 5 days (range 0-50) and 57 days (range 5-365), respectively. Those who took significantly longer to initiate ART were aged <35 years, identified as heterosexual, had less than university-level education, or were unemployed. No factor was found to significantly affect time to undetectability. CONCLUSION: Despite the provision of free B/F/TAF, several SDH were linked to delays in ART initiation. However, once initiated and engaged, migrants living with HIV reached HIV undetectability efficiently. Findings provide preliminary support for adopting this care model with migrants living with HIV and suggest that SDH should be considered when designing clinical interventions for more equitable outcomes.

Switch to a raltegravir-based antiretroviral regimen in people with HIV and non-alcoholic fatty liver disease: A randomized controlled trial.

INTRODUCTION: The effect of antiretroviral therapy (ART), particularly integrase strand transfer inhibitors (INSTIs), on non-alcoholic fatty liver disease (NAFLD) in people with HIV remains unclear. We evaluated the effect of switching non-INSTI backbone antiretroviral medications to raltegravir on NAFLD and metabolic parameters. MATERIALS AND METHODS: This was a single-centre, phase IV, open-label, randomized controlled clinical trial. People living with HIV with NAFLD and undetectable viral load while receiving a non-INSTI were randomized 1:1 to the switch arm (raltegravir 400 mg twice daily) or the control arm (continuing ART regimens not containing INSTI). NAFLD was defined as hepatic steatosis by controlled attenuation parameter ≥238 dB/m in the absence of significant alcohol use and viral hepatitis co-infections. Cytokeratin 18 was used as a biomarker of non-alcoholic steatohepatitis. Changes over time in outcomes were quantified as standardized mean differences (SMDs), and a generalized linear mixed model was used to compare outcomes between study arms. RESULTS: A total of 31 people with HIV (mean age 54 years, 74% male) were randomized and followed for 24 months. Hepatic steatosis improved between baseline and end of follow-up in both the switch (SMD -43.4 dB/m) and the control arm (-26.6 dB/m); the difference between arms was not significant. At the end of follow-up, aspartate aminotransferase significantly decreased in the switch arm compared with the control arm (SMD -9.4 vs. 5.5 IU/L). No changes in cytokeratin 18, body mass index, or lipids were observed between study arms. DISCUSSION: Switching to a raltegravir-based regimen improved aspartate aminotransferase but seemed to have no effect on NAFLD, body weight, and lipids compared with remaining on any other ART.

Role of fatty liver in the epidemic of advanced chronic liver disease among people with HIV: protocol for the Canadian LIVEHIV multicentre prospective cohort.

INTRODUCTION: Advanced chronic liver disease (ACLD) is a major cause of death for people with HIV (PWH). While viral hepatitis coinfections are largely responsible for this trend, metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging concern for PWH. We aimed to assess the contribution of MASLD to incident ACLD in PWH. METHODS AND ANALYSIS: This multicentre prospective observational cohort study will enrol 968 consecutive HIV monoinfected patients from four Canadian sites, excluding subjects with alcohol abuse, liver disease other than MASLD, or ACLD at baseline. Participants will be followed annually for 4 years by clinical evaluation, questionnaires, laboratory testing and Fibroscan to measure liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). The primary outcome will be incidence of ACLD, defined as LSM>10 kPa, by MASLD status, defined as CAP≥285 dB/m with at least one metabolic abnormality, and to develop a score to classify PWH according to their risk of ACLD. Secondary outcomes will include health-related quality of life (HRQoL) and healthcare resource usage. Kaplan-Meier survival method and Cox proportional hazards regression will calculate the incidence and predictors of ACLD, respectively. Propensity score methods and marginal structural models will account for time-varying exposures. We will split the cohort into a training set (to develop the risk score) and a validation set (for validation of the score). HRQoL scores and healthcare resource usage will be compared by MASLD status using generalised linear mixed effects model. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committees of all participating institutions. Written informed consent will be obtained from all study participants. The results of this study will be shared through scientific publications and public presentations to advocate for the inclusion of PWH in clinical trials of MASLD-targeted therapies and case-finding of ACLD in PWH.

Pathways From HIV-Related Stigma, Racial Discrimination, and Gender Discrimination to HIV Treatment Outcomes Among Women Living With HIV in Canada: Longitudinal Cohort Findings.

BACKGROUND: HIV-related stigma, gender discrimination, and racial discrimination harm mental health and hamper HIV treatment access for women living with HIV. Maladaptive coping strategies, such as substance use, can further worsen HIV treatment outcomes, whereas resilience can improve HIV outcomes. We examined resilience and depression as mediators of the relationship between multiple stigmas and HIV treatment outcomes among women living with HIV. SETTING: Ontario, British Columbia, and Quebec, Canada. METHODS: We conducted a longitudinal study with 3 waves at 18-month intervals. We used structural equation modeling to test the associations of multiple stigmas (HIV-related stigma, racial discrimination, and gender discrimination) or an intersectional construct of all 3 stigmas at wave 1 on self-reported HIV treatment cascade outcomes (≥95% antiretroviral treatment [ART] adherence, undetectable viral load) at wave 3. We tested depression and resilience at wave 2 as potential mediators and adjusted for sociodemographic factors. RESULTS: There were 1422 participants at wave 1, half of whom were Black (29%) or Indigenous (20%). Most participants reported high ART adherence (74%) and viral suppression (93%). Racial discrimination was directly associated with having a detectable viral load, while intersectional stigma was directly associated with lower ART adherence. Resilience mediated associations between individual and intersectional stigmas and HIV treatment cascade outcomes, but depression did not. Racial discrimination was associated with increased resilience, while intersectional and other individual stigmas were associated with reduced resilience. CONCLUSION: Race, gender and HIV-related stigma reduction interventions are required to address intersectional stigma among women living with HIV. Including resilience-building activities in these interventions may improve HIV treatment outcomes.

Sexual Satisfaction of Midlife Women Living With HIV in Canada: A Prospective Cohort Analysis.

BACKGROUND: Although sexual activity and function decline in older women living with HIV, positive dimensions of sexual health, such as satisfaction, are relatively unexplored. We evaluated the prevalence of sexual satisfaction for midlife women with HIV and assessed its relation to women's physical, mental, and sociostructural experiences. SETTING: We studied women in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) over 3 survey waves (2013-2018). METHODS: We included women living with HIV aged ≥45 years who reported ever having consensual sex. Sexual satisfaction was assessed using an item from the Sexual Satisfaction Scale for Women and was dichotomized into satisfactory ("completely/very/reasonably satisfactory") and not satisfactory ("not very/not at all satisfactory"). Probable depression was based on CES-D ≥10. Multivariable logistic regression and fixed effects models determined correlates of sexual satisfaction. Reasons for sexual inactivity and alternate forms of sexual expression were also explored. RESULTS: Among 508 midlife women, 61% were satisfied with their sexual lives at baseline. Women with probable depression had lower odds of sexual satisfaction than those without (aOR: 0.44; 95% CI: 0.27 to 0.71) and worsening depressive symptoms over time were associated with poorer sexual satisfaction ( P = 0.001). Increased sexual activity was associated with higher sexual satisfaction (aOR: 2.75; 95% CI: 1.54 to 4.91); however, 51% of women reporting sexual satisfaction were sexually inactive. Sexually inactive women engaged in alternate forms of sexual expression such as self-pleasure (37%) and intimate relationships without sex (13%). CONCLUSION: Midlife women with HIV have high rates of sexual satisfaction, even in the absence of sexual activity. Depressive symptoms were closely associated with sexual dissatisfaction, alerting providers to the importance of screening for depression and sexual health together.

Practices, support and stigma related to infant feeding and postpartum engagement in care among women living with HIV in Canada.

Background: Breastfeeding is not recommended for women living with HIV (WLWH) in Canada. We described the prevalence of breastfeeding and explored experiences of care, support, and stigma related to infant feeding. Setting: Quebec, Ontario, and British Columbia (Canada). Methods: Data were obtained from the HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS) surveys, conducted between 2013 and 2018. Results: Breastfeeding was reported by 73.5% of the 786 women who delivered before HIV diagnosis and 7.3% of the 289 women who delivered after HIV diagnosis. Among them, earlier year of delivery, delivery outside of Canada, and African, Caribbean, Black ethnicity were independently associated with increased odds of breastfeeding. Among WLWH who had a live birth during the last year, 77% (40/52) felt that they had received support regarding infant feeding practices, and 77% (23/30) were concerned that not breastfeeding could lead to them being identified as WLWH. Among 71 women within one year postpartum at any one of the study waves, 89% reported having an undetectable viral load. Conclusion: Breastfeeding experiences were common among WLWH, most often prior to HIV diagnosis. Fear of unintentional HIV status disclosure when not breastfeeding and challenges to maintain an undetectable HIV viral load are important issues to address during postpartum care.

Self-reported Human Papillomavirus Vaccination and Vaccine Effectiveness Among Men Who Have Sex with Men: A Quantitative Bias Analysis.

BACKGROUND: Self-report of human papillomavirus (HPV) vaccination has ~80-90% sensitivity and ~75-85% specificity. We measured the effect of nondifferential exposure misclassification associated with self-reported vaccination on vaccine effectiveness (VE) estimates. METHODS: Between 2017-2019, we recruited sexually active gay, bisexual, and other men who have sex with men aged 16-30 years in Canada. VE was derived as 1-prevalence ratio × 100% for prevalent anal HPV infection comparing vaccinated (≥1 dose) to unvaccinated men using a multivariable modified Poisson regression. We conducted a multidimensional and probabilistic quantitative bias analysis to correct VE estimates. RESULTS: Bias-corrected VE estimates were relatively stable across sensitivity values but differed from the uncorrected estimate at lower values of specificity. The median adjusted VE was 27% (2.5-97.5th simulation interval = -5-49%) in the uncorrected analysis, increasing to 39% (2.5-97.5th simulation interval = 2-65%) in the bias-corrected analysis. CONCLUSION: A large proportion of participants erroneously reporting HPV vaccination would be required to meaningfully change VE estimates.

CD4/CD8 Ratio Outcome According to the Class of the Third Active Drug in Antiretroviral Therapy Regimens: Results From the Quebec Human Immunodeficiency Virus Cohort Study.

BACKGROUND: The impact of different therapeutic classes of drugs in antiretroviral therapy (ART) regimens on the CD4/CD8 ratio is not well documented in people treated for HIV. The objective of this study was to analyze the long-term effect of exposure to integrase strand transfer inhibitor (INSTI) on CD4/CD8 ratio compared with nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) among ART-treated persons with HIV (PWH). METHODS: Data from the Quebec HIV Cohort collected from 31 August 2017 were used. Our analysis included all patients in the cohort who received a first or subsequent ART regimen composed of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and a third active drug of a different class (NNRTI, PI, or INSTI) for at least 16 weeks. Marginal structural Cox models were constructed to estimate the effect of different therapeutic classes on the CD4/CD8 ratio outcome. RESULTS: Among the 3907 eligible patients, 972 (24.9%), 1996 (51.1%), and 939 (24.0%) were exposed to an ART regimen whose third active agent was an NNRTI, PI, or INSTI, respectively. The total follow-up time was 13 640.24 person-years. The weighted hazard ratio for the association between the third active class and CD4/CD8 ratio ≥1 was .56 (95% confidence interval [CI]: .48-.65) for patients exposed to NNRTI + 2 NRTIs and .41 (95% CI: .35-.47) for those exposed to PI + 2 NRTIs, compared with those exposed INSTI + 2 NRTIs. CONCLUSIONS: For people treated for HIV, INSTI-based ART appears to be associated with a higher CD4/CD8 ratio than NNRTI and PI-based ART.

Vaccine Effectiveness Against 12-Month Incident and Persistent Anal Human Papillomavirus Infection Among Gay, Bisexual, and Other Men Who Have Sex With Men.

BACKGROUND: Real-world evidence of human papillomavirus (HPV) vaccine effectiveness (VE) against longitudinal outcomes is lacking among gay, bisexual, and other men who have sex with men (GBM). We compared 12-month incidence and persistence of anal HPV infection between vaccinated and unvaccinated GBM. METHODS: We recruited GBM aged 16-30 years in Montreal, Toronto, and Vancouver, Canada, from 2017 to 2019. Participants were followed over a median of 12 months (interquartile range, 12-13 months). Participants self-reported HPV vaccination and self-collected anal specimens for HPV DNA testing. We calculated prevalence ratios (PR) for 12-month cumulative incidence and persistence with ≥1 quadrivalent vaccine type (HPV 6/11/16/18) between vaccinated (≥1 dose at baseline) and unvaccinated participants using a propensity score-weighted, modified Poisson regression. RESULTS: Among 248 participants, 109 (44.0%) were vaccinated at baseline, of whom 62.6% received 3 doses. PRs for HPV 6/11/16/18 were 0.56 (95% confidence interval [CI], .24-1.31) for cumulative incidence and 0.53 (95% CI, .25-1.14) for persistence. PRs were 0.23 (95% CI, .05-1.03) and 0.08 (95% CI, .01-.59) for incidence and persistence, respectively, among participants who received their first dose at age ≤23 years and 0.15 (95% CI, .03-.68) and 0.12 (95% CI, .03-.54) among participants who were sexually active for ≤5 years before vaccination. CONCLUSIONS: Findings support national recommendations for HPV vaccination at younger ages or soon after sexual debut.

Influence of letermovir treatment on gut inflammation in people living with HIV on antiretroviral therapy: protocol of the open-label controlled randomised CIAO study.

INTRODUCTION: Chronic cytomegalovirus (CMV) infection is very frequent in people living with HIV (PLWH). High anti-CMV IgG titres, which may be linked to transient CMV replication, have been associated with earlier mortality, CD8 T-cell expansion, lower CD4/CD8 ratio and increased T-cell senescence. We previously showed that anti-CMV IgG titres correlated with gut permeability in PLWH on antiretroviral therapy (ART), which was associated with microbial translocation, systemic inflammation and non-infectious/non-AIDS comorbidities. Letermovir, a novel anti-CMV drug with a good safety profile, was recently approved for anti-CMV prophylaxis in allogeneic haematopoietic stem cell transplant recipients. A drastic and selective reduction of both low-grade replication and clinically significant CMV infections, combined with an improved immune reconstitution have been reported. In vitro, letermovir prevented CMV-induced epithelial disruption in intestinal tissues. Based on these findings, we aim to assess whether letermovir could inhibit CMV subclinical replication in CMV-seropositive PLWH receiving ART and, in turn, decrease CMV-associated gut damage and inflammation. METHOD AND ANALYSIS: We will conduct a multi-centre, open-label, randomised, controlled clinical trial, including a total of 60 CMV-seropositive ART-treated PLWH for at least 3 years, with a viral load <50 copies/mL and CD4+ count >400 cells/µL. Forty participants will be randomised to receive letermovir for 14 weeks and 20 participants will receive standard of care (ART) alone. Plasma, pheripheral blood mononuclear cells (PBMCs), and stool samples will be collected. Colon biopsies will be collected in an optional substudy. We will assess the effect of letermovir on gut damage, microbial translocation, inflammation and HIV reservoir size. ETHICS AND DISSEMINATION: The study was approved by Health Canada and the Research Ethics Boards of the McGill University Health Centre (MUHC-REB, protocol number: MP37-2022-8295). Results will be made available through publications in open access peer-reviewed journals and through the CIHR/CTN website. TRIAL REGISTRATION NUMBER: NCT05362916.

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

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.

HIV care cascade for women living with HIV in the Greater Toronto Area versus the rest of Ontario and Canada.

BACKGROUND: The Greater Toronto Area (GTA) is home to 39% of Canada's population living with HIV. To identify gaps in access and engagement in care and treatment, we assessed the care cascade of women living with HIV (WLWH) in the GTA versus the rest of Ontario and Canada (in this case: Quebec and British Columbia). METHODS: We analyzed 2013-2015 self-reported baseline data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study for six care cascade stages: linked to care, retained in care, initiated antiretroviral therapy (ART), currently on ART, ART adherence (≥90%), and undetectable (<50 copies/mL). Multivariable logistic regression was used to reveal associations with being undetectable. RESULTS: Comparing the GTA to the rest of Ontario and Canada, respectively: 96%, 98%, 100% were linked to care; 92%, 94%, 98% retained in care; 72%, 89%, 96% initiated ART; 67%, 81%, 90% were currently using ART; 53%, 66%, 77% were adherent; 59%, 69%, 81% were undetectable. Factors associated with viral suppression in the multivariable model included: living outside of the GTA (Ontario: aOR = 1.72, 95% CI: 1.09-2.72; Canada: aOR = 2.42, 95% CI: 1.62-3.62), non-Canadian citizenship (landed immigrant/permanent resident: aOR = 3.23, 95% CI: 1.66-6.26; refugee/protected person/other status: aOR = 4.77, 95% CI: 1.96-11.64), completed high school (aOR = 1.77, 95% CI: 1.15-2.73), stable housing (aOR = 2.13, 95% CI: 1.33-3.39), income of ≥$20,000 (aOR = 1.52, 95% CI: 1.00-2.31), HIV diagnosis <6 years (6-14 years: aOR = 1.75, 95% CI: 1.16-2.63; >14 years: aOR = 1.87, 95% CI: 1.19-2.96), and higher resilience (aOR = 1.02, 95% CI: 1.00-1.04). CONCLUSION: WLWH living in the GTA had lower rates of viral suppression compared to the rest of Ontario and Canada even after adjustment of age, ethnicity, and HIV diagnosis duration. High-impact programming for WLWH in the GTA to improve HIV outcomes are greatly needed.

Efficacy of a Carrageenan Gel in Increasing Clearance of Anal Human Papillomavirus Infections in Men: Interim Analysis of a Double-Blind, Randomized Controlled Trial.

Preclinical studies have demonstrated carrageenan's anti-human papillomavirus (HPV) activity. We assessed efficacy of a carrageenan-based gel compared to a placebo gel in increasing the clearance of anal HPV infections among gay, bisexual, and other men who have sex with men (gbMSM). Of 255 enrolled gbMSM, 134 were HPV positive at baseline and had valid HPV results for ≥2 visits. Carrageenan did not differ from placebo in clearing all baseline infections (hazard ratio, 0.84 [95% confidence interval, .31-2.27]), based on having 2 consecutive HPV-negative visits following at least 1 HPV-positive visit. There were no remarkable differences for analyses at the HPV type level or by human immunodeficiency virus status. CLINICAL TRIALS REGISTRATION: NCT02354144.

Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

Age-Specific Prevalence of Anal and Cervical Human Papillomavirus Infection and High-Grade Lesions in 11 177 Women by Human Immunodeficiency Virus Status: A Collaborative Pooled Analysis of 26 Studies.

BACKGROUND: Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. METHODS: We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology. RESULTS: In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+. CONCLUSIONS: Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.