BACKGROUND:Tecovirimat (TPOXX) is an antiviral authorized for the treatment of mpox infections in Canada, but recent clinical trials found it has no impact on symptom duration. METHODS:We conducted a prospective cohort study of individuals diagnosed with mpox in Toronto, Canada. Skin lesion swabs were collected weekly to quantify infectious monkeypox virus (MPXV) shedding through cell culture. The presence of antiviral resistance mutations was assessed by PCR and sequencing the F13L gene. RESULTS:Among 17 participants, 9 received tecovirimat, with a median initiation time of 14 days post-symptom onset. Infectious MPXV was detected in 31% (17/55) of lesion swabs from tecovirimat-treated participants and 32% (20/62) from untreated individuals. Shedding kinetics were similar between groups, with persistent infectious virus detected in several participants beyond 2 weeks of symptoms. Despite more than 7 days after tecovirimat initiation, 4 treated participants still shed viable virus in at least 1 sampled lesion, including up to 15 days after tecovirimat initiation. No known resistance mutations were identified in viral sequences from a subset of lesion swabs from both treated and untreated individuals, suggesting that tecovirimat resistance mutations were not widely circulating in Toronto during the 2022 outbreak. CONCLUSIONS:Our findings suggest that tecovirimat does not significantly impact the duration of infectious MPXV shedding from skin lesions, aligning with recent randomized trial results. These findings highlight the need for alternative antiviral strategies and continued genomic surveillance to monitor resistance emergence.

Advances in treatment and care have extended the life expectancy of people living with HIV. Nevertheless, comorbidities are common and may result in health-related challenges, known as disability, in everyday life. Rehabilitation strategies such as physical activity may help to mitigate disability. Our aim was to characterize comorbidity profiles and examine their relationship with disability and physical activity among a cohort of older adults living with HIV in Canada. We conducted a cross-sectional analysis of data collected from older adults living with HIV aged 65 years and older and enrolled in the Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study. We examined the presence of 14 individual comorbidities and their combinations. Hierarchical linear regression was used to assess the associations between number of comorbidities, disability (Stanford Health Assessment Questionnaire Disability Index), and physical activity (Rapid Assessment of Physical Activity Aerobic Scale) while sequentially adjusting for intrinsic (personal attributes) and extrinsic (perceived HIV stigma and social support) contextual factors. Among the 516 participants (median age = 69 years, 25th − 75th percentiles: 67–73), most were identified as male (90

The COVID-19 pandemic was an event involving an actual threat of death, serious injury, or harm to the integrity of self or others, which could have served as a precipitant for unmasking symptoms of post-traumatic stress disorder (PTSD). Persons living with HIV and those with hepatitis C (HCV) coinfection could be at increased risk of PTSD symptoms after a traumatic event, given their lifetime experiences of trauma, stigma, poverty, mental health conditions, and substance use. We measured PTSD symptoms at three time points during the COVID-19 pandemic using a 17-item questionnaire in two established cohorts of persons living with HIV in Canada-those with HCV coinfection and those aging with HIV-groups at risk for having symptoms. We found that twice as many persons in the HCV coinfection cohort had moderate to severe PTSD symptoms at baseline relative to the aging cohort (49% vs. 25%) and that these percentages remained high in the coinfection cohort but declined in the aging cohort with time. Notably, those who self-reported depression had increased rates of PTSD symptoms over time. Our data points to the potential long-lasting impact that the COVID-19 pandemic or other traumatic events could have on the mental health of persons living with HIV and those with coinfection, especially among those with underlying depression. We stress the need for increased awareness and management strategies of vulnerable groups during times of trauma.

Background: Doravirine and islatravir is an investigational, once-daily, single-tablet regimen containing two potent antiretrovirals with complementary mechanisms of action and resistance profiles. We aimed to evaluate the efficacy and safety of switching from stable, oral antiretroviral therapy (ART) to the fixed combination of doravirine (100 mg) and islatravir (025 mg) in virologically suppressed adults living with HIV-1. Methods: This phase 3, randomised, active-controlled, open-label, non-inferiority trial was conducted at 53 research, community, and hospital-based clinics in eight countries: Australia, Canada, Colombia, Japan, South Africa, Switzerland, the UK, and the USA. Adults (aged >= 18 years) with a viral load of fewer than 50 copies of HIV-1 RNA per mL on any oral, two-drug or three-drug ART regimen for at least 3 months, with no history of treatment failure, known resistance to doravirine, or active hepatitis B infection, were randomly assigned (2:1) according to a computer-generated randomisation schedule (block size three) to receive oral doravirine (100 mg) and islatravir (025 mg) once daily or to continue baseline ART for 48 weeks. Randomisation was stratified by the anchor antiretroviral drug class (integrase strand-transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor, or protease inhibitor) in the baseline regimen. The primary endpoint (assessed in all treated participants) was the percentage of participants with a viral load of 50 copies per mL or higher at week 48 (analysed according to the US Food and Drug Administration snapshot approach); non-inferiority would be concluded if the upper bound of the multiplicity-adjusted 95% CI for the treatment difference was less than 4%. The safety analysis population included all randomly assigned participants who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, NCT05631093, and is ongoing but closed to enrolment. Findings: Between Feb 20 and Oct 24, 2023, 614 individuals were screened for eligibility, of whom 553 were randomly assigned to receive doravirine and islatravir (n=368) or baseline ART (n=185). 551 participants received at least one dose of allocated medication: 366 in the doravirine and islatravir group and 185 in the baseline ART group. Of these 551 participants, 332 (60%) were assigned male and 219 (40%) were assigned female at birth, and the median age was 51 years (IQR 41-59); 250 (45%) identified as Black or African American and 80 (15%) identified as Hispanic, Latino, or Latina. Doravirine and islatravir showed non-inferiority at week 48, with viral loads of 50 copies per mL or higher in five (14%) of 366 participants versus nine (49%) of 185 participants on baseline ART (difference -36% [multiplicity-adjusted 95% CI -78 to -08]). Treatment-related adverse events were more common with doravirine and islatravir (44 [120%] of 366 participants) than with baseline ART (nine [49%] of 185 participants; difference 72 [95% CI 22 to 116]). Rates were similar in the doravirine and islatravir group and the baseline ART group for any adverse event (795% [291 of 366 participants] vs 838% [155 of 185 participants]; difference -43 [-107 to 28]), serious adverse events (63% [23] vs 49% [nine]; 14 [-32 to 52]), and discontinuation due to adverse events (05% [two] vs 22% [four]; -16 [-49 to 02]). One death occurred (in the baseline ART group) and was not considered treatment-related. No participants discontinued treatment as a result of protocol-specified declines in CD4 cell or total lymphocyte counts. Interpretation: Doravirine and islatravir is efficacious and well tolerated and would represent the first non-INSTI-based, two-drug regimen for HIV-1 treatment. With increasing concern over the potential development of widespread INSTI resistance, this once-daily, oral, single-tablet regimen could be a potential option for people living with HIV-1 requiring a change to their antiretroviral regimen. The safety and efficacy findings support the ongoing development of islatravir, a drug with long-acting potential.

BACKGROUND:Human papillomavirus (HPV) testing has been implemented in many organized cervix screening programs; however, understanding how this screening methodology affects rates of colposcopy and further follow-up procedures remains underexplored, especially among women with HIV. In the absence of HPV screening program data in British Columbia (BC), Canada, we sought to determine HPV prevalence and estimates for colposcopies among a cohort of women with HIV using the BC Cervix Screening algorithm. SETTING:HPV data were collected and analyzed from a prospective HPV vaccine immunogenicity cohort study of women with HIV from 14 sites of HIV care across Canada from 2008 to 2015. METHODS:HPV data were obtained during the screening (month -3), baseline (month 0), month 12, and month 24 time points (Linear Array assay). Participant demographic and clinical characteristics (CD4 + count, HIV viral load, etc.) were assessed to determine associations between HPV prevalence and estimates for colposcopy using rate ratios and 95% confidence intervals. RESULTS:Overall, 47.2% of participants had oncogenic HPV detected at screening which would result in a colposcopy referral. In total, 15.9% of participants had oncogenic HPV detected at screening, month 12, and month 24 time points, which would result in 3 consecutive referrals to colposcopy. Participants with repeat oncogenic HPV detected were less likely to have a suppressed HIV viral load compared with participants without oncogenic HPV detected. CONCLUSIONS:Results of this study suggest that HPV testing will result in a high proportion of referrals to colposcopy and follow-up procedures among women with HIV, which will require preparation and planning. Further work is needed to provide the appropriate support and education for women with HIV when incorporating HPV testing into cervix screening programs.

Background and Aims:Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in people with HIV (PWH), yet its impact on health-related quality of life (HRQoL) remains poorly characterized. We evaluated the association between MASLD and both generic and liver-specific HRQoL. Methods:We conducted a cross-sectional analysis within a national multicenter cohort of PWH. MASLD was defined as hepatic steatosis (controlled attenuation parameter >248 dB/m) plus at least metabolic comorbidity and significant liver fibrosis as liver stiffness measurement ≥8 kPa on FibroScan. Generic HRQoL was assessed using the Short Form-36 and liver-specific HRQoL using the Chronic Liver Disease Questionnaire (CLDQ). Adjusted estimated mean differences were estimated using multivariable linear regression. Results:Among 519 participants, the prevalence of MASLD and significant liver fibrosis was 41.4% and 7.2%, respectively. MASLD was independently associated with lower generic HRQoL, including reduction of physical functioning (-4.6; 95% confidence interval [CI] -9.12 to -0.01) and general health (-4.5; 95% CI -8.58 to -0.48) on the Short Form-36. Liver-specific HRQoL was more affected; MASLD was associated with a lower overall CLDQ score (-0.29; 95% CI -0.49 to -0.09), driven by worse fatigue, systemic symptoms, emotional symptoms, and worry. Among PWH with MASLD, increasing metabolic comorbidity burden was associated with a dose-response decline in physical HRQoL, whereas liver-specific HRQoL did not differ across comorbidity strata. Significant fibrosis was associated with lower CLDQ activity (-0.62; 95% CI -1.20 to -0.05) and worry (-0.60; 95% CI -1.15 to -0.05). Conclusion:In PWH, MASLD is associated with impaired HRQoL, particularly fatigue, systemic symptoms, and emotional well-being. Greater metabolic burden and liver fibrosis further worsen patient-reported outcomes.

BACKGROUND:Doravirine and islatravir is an investigational, once-daily, single-tablet regimen containing two potent antiretrovirals with complementary mechanisms of action and resistance profiles. We aimed to evaluate the efficacy and safety of switching from stable, oral antiretroviral therapy (ART) to the fixed combination of doravirine (100 mg) and islatravir (0·25 mg) in virologically suppressed adults living with HIV-1. METHODS:This phase 3, randomised, active-controlled, open-label, non-inferiority trial was conducted at 53 research, community, and hospital-based clinics in eight countries: Australia, Canada, Colombia, Japan, South Africa, Switzerland, the UK, and the USA. Adults (aged ≥18 years) with a viral load of fewer than 50 copies of HIV-1 RNA per mL on any oral, two-drug or three-drug ART regimen for at least 3 months, with no history of treatment failure, known resistance to doravirine, or active hepatitis B infection, were randomly assigned (2:1) according to a computer-generated randomisation schedule (block size three) to receive oral doravirine (100 mg) and islatravir (0·25 mg) once daily or to continue baseline ART for 48 weeks. Randomisation was stratified by the anchor antiretroviral drug class (integrase strand-transfer inhibitor [INSTI], non-nucleoside reverse transcriptase inhibitor, or protease inhibitor) in the baseline regimen. The primary endpoint (assessed in all treated participants) was the percentage of participants with a viral load of 50 copies per mL or higher at week 48 (analysed according to the US Food and Drug Administration snapshot approach); non-inferiority would be concluded if the upper bound of the multiplicity-adjusted 95% CI for the treatment difference was less than 4%. The safety analysis population included all randomly assigned participants who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, NCT05631093, and is ongoing but closed to enrolment. FINDINGS:Between Feb 20 and Oct 24, 2023, 614 individuals were screened for eligibility, of whom 553 were randomly assigned to receive doravirine and islatravir (n=368) or baseline ART (n=185). 551 participants received at least one dose of allocated medication: 366 in the doravirine and islatravir group and 185 in the baseline ART group. Of these 551 participants, 332 (60%) were assigned male and 219 (40%) were assigned female at birth, and the median age was 51 years (IQR 41-59); 250 (45%) identified as Black or African American and 80 (15%) identified as Hispanic, Latino, or Latina. Doravirine and islatravir showed non-inferiority at week 48, with viral loads of 50 copies per mL or higher in five (1·4%) of 366 participants versus nine (4·9%) of 185 participants on baseline ART (difference -3·6% [multiplicity-adjusted 95% CI -7·8 to -0·8]). Treatment-related adverse events were more common with doravirine and islatravir (44 [12·0%] of 366 participants) than with baseline ART (nine [4·9%] of 185 participants; difference 7·2 [95% CI 2·2 to 11·6]). Rates were similar in the doravirine and islatravir group and the baseline ART group for any adverse event (79·5% [291 of 366 participants] vs 83·8% [155 of 185 participants]; difference -4·3 [-10·7 to 2·8]), serious adverse events (6·3% [23] vs 4·9% [nine]; 1·4 [-3·2 to 5·2]), and discontinuation due to adverse events (0·5% [two] vs 2·2% [four]; -1·6 [-4·9 to 0·2]). One death occurred (in the baseline ART group) and was not considered treatment-related. No participants discontinued treatment as a result of protocol-specified declines in CD4 cell or total lymphocyte counts. INTERPRETATION:Doravirine and islatravir is efficacious and well tolerated and would represent the first non-INSTI-based, two-drug regimen for HIV-1 treatment. With increasing concern over the potential development of widespread INSTI resistance, this once-daily, oral, single-tablet regimen could be a potential option for people living with HIV-1 requiring a change to their antiretroviral regimen. The safety and efficacy findings support the ongoing development of islatravir, a drug with long-acting potential. FUNDING:Merck Sharp & Dohme, a subsidiary of Merck & Co.

ABSTRACT Introduction Female sex workers (FSWs) are at higher risk of sexually transmitted infections (STIs), including HIV, due to occupation‐related factors further exacerbated by gender‐specific vulnerability and marginalization. Stigma and fear of disclosing their occupation pose multiple barriers that limit access to sexual and reproductive health (SRH) services, as well as HIV testing, prevention and treatment. We describe the implementation of a tailored comprehensive SRH‐HIV prevention and care model for FSWs, and report HIV prevalence, pre‐exposure prophylaxis (PrEP) uptake and HIV treatment outcomes in our cohort. Methods “MAS por Nosotras” adopted a co‐creation and co‐production approach including a formative phase (focus groups with FSWs and semistructured interviews with stakeholders), and a prospective cohort of FSWs at a non‐governmental organization (NGO) in Argentina. Our conceived model focused on HIV treatment and combination prevention, including STI testing, cancer screening, contraception counselling and vaccination. Demographic, psychosocial and clinical information were collected. Results Between June 2023 and March 2024, 200 cisgender and transgender FSWs were enrolled in the prospective cohort, with a 66.5% retention rate at 6 months. HIV prevalence was 18.5% (34.3% in transgender women [TGW] and 3% in cisgender women [CGW]), with only one incident case during follow‐up. Among those with known HIV, 61% had a viral load <50 copies/mL. PrEP acceptance was higher in TGW (55.6%) versus 30.5% in CGW, but PrEP persistence was low (69% discontinued), especially in CGW. Nearly 78.5% of participants indicated they would be very likely to recommend the care package to their peers. Conclusions “MAS por Nosotras” implemented a community‐linked, gender‐informed integrated SRH‐HIV model of care, articulated with community‐based organizations, public health and an NGO research centre that facilitated access to HIV testing, prevention and treatment initiation or re‐engagement. We found a high prevalence of HIV, particularly among TGW, and low PrEP knowledge and use, especially among CGW. Our data reflect the need of expanding and tailoring HIV prevention strategies with a community‐focused approach. This proposed integrated SRH‐HIV model addressed these needs and generated preliminary evidence regarding operational feasibility and acceptability that may inform models to help close prevention and treatment gaps for FSWs in Latin America.

In two Phase 3 studies, switching to doravirine/islatravir (DOR/ISL, 100 mg/0.25 mg), an investigational once-daily regimen for HIV treatment, was non-inferior for efficacy with a safety profile comparable to continuing baseline antiretroviral therapy (bART) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) at Week 48 (W48). Demographic parameters might affect the efficacy or adverse event (AE) profile of an antiretroviral regimen. This subgroup analysis was performed to evaluate the efficacy and safety of DOR/ISL by sex assigned at birth. Adults with HIV-1 RNA < 50 copies/mL receiving stable oral bART (MK-8591A-051 [P051]; NCT05631093) or BIC/FTC/TAF (MK-8591A-052 [P052]; NCT05630755) for ≥3 months were randomized (2:1) to switch to DOR/ISL (100 mg/0.25 mg), or to continue bART (P051) or BIC/FTC/TAF (P052). For P051+P052, efficacy results were pooled for both the DOR/ISL arms and the comparator arms (pooled comparator) and were summarized by sex assigned at birth (female or male) through W48. AEs and weight were reported by sex subgroup for each study. Across both studies (P051+P052), 708 participants switched to DOR/ISL and 356 continued bART or BIC/FTC/TAF (pooled comparator); overall 30.9% were female. At W48, the proportion of participants with HIV-1 RNA < 50 copies/mL was similar between females and males in the pooled DOR/ISL group (94.2% vs 93.4%) and generally similar to the pooled comparator group (90.3% vs 94.1%; Figure). In open-label P051 in all treatment groups, females had consistently higher rates of AEs and drug-related AEs than males (Table). In double-blind P052, AEs and drug-related AEs were comparable for females and males in the DOR/ISL group. The rates of discontinuation due to AEs by sex were low and < 5% in all treatment groups. For females and males who switched to DOR/ISL, change in weight from baseline was minimal (mean percent change range in sex subgroups −1.29% to 1.95%; Table). There were no clinically meaningful differences in weight change between females and males. At W48, switching to DOR/ISL (100 mg/0.25 mg) demonstrated high efficacy and was generally well tolerated in females and males living with HIV-1. Princy N. Kumar, MD, Gilead Sciences, Inc (Foster City, CA, USA): Grant/Research Support|Gilead Sciences, Inc (Foster City, CA, USA): Medical writing support provided by Aspire Scientific (Bollington, UK)|Gilead Sciences, Inc (Foster City, CA, USA): Stocks/Bonds (Public Company) Sharon Walmsley, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: CME Speaking Engagements|GSK: Advisor/Consultant|GSK: Grant/Research Support|GSK: CME Speaking Engagements|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: CME Speaking Engagements|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: CME Speaking Engagements|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: CME Speaking Engagements Alexandra Calmy, MD, PhD, Gilead Sciences: Grant/Research Support|MSD: Grant/Research Support|ViiV Healthcare: Grant/Research Support Cynthia C. Brinson, MD, Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Honoraria|Gilead Sciences, Inc.: Medical writing funds|GSK: Grant/Research Support|ViiV: Grant/Research Support Chloe Orkin, MBChB, FRCP, MD, AstraZeneca: Grant/Research Support|Bavarian Nordic: Payment directly from commercial firms for lecture(s), including service on speakers’ bureaus; Travel Reimbursements|Gilead Sciences, Inc: Grant/Research Support|Gilead Sciences, Inc: Payment directly from commercial firms for lecture(s), including service on speakers’ bureaus; Travel reimbursement|GlaxoSmithKline,: Grant/Research Support|GlaxoSmithKline,: Payment directly from commercial firms for lecture(s), including service on speakers’ bureaus ; Travel Reimbursement|Janssen: Grant/Research Support|Janssen: Payment directly from commercial firms for lecture(s), including service on speakers’ bureaus|MSD Pty LTD: Grant/Research Support|MSD Pty LTD: Payment directly from commercial firms for lecture(s), including service on speakers’ bureaus|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Payment directly from commercial firms for lecture(s), including service on speakers’ bureaus ; Travel Reimbursements Anjana Grandhi, PhD, Merck & Co., Inc.: Employment|Merck & Co., Inc.: Stocks/Bonds (Public Company) Monica Fuszard, MS, Merck & Co.: Employment Stephanie O. Klopfer, PhD, Merck & Co., Inc: Employment|Merck & Co., Inc: Stocks/Bonds (Public Company) Rima Lahoulou, n/a, MSD: Employment|MSD: Stocks/Bonds (Private Company) Luisa M. Stamm, MD, PhD, Merck & Co., Inc.: Employment|Merck & Co., Inc.: Stocks/Bonds (Public Company) Michelle C. Fox, MD, Merck & Co., Inc.: Employment|Merck & Co., Inc.: Stocks/Bonds (Public Company) Jason Y. Kim, MD, MSCE, Merck & Co.: Employment|Merck & Co.: Stocks/Bonds (Public Company)

Background:In randomized trials, doravirine (DOR) appears relatively weight-neutral, while tenofovir DF (TDF) may be weight-suppressive. Here we designed a prospective, observational pilot study to assess the impact of switching to DOR/3TC/TDF on weight trajectory in patients with significant integrase inhibitor (INSTI)-associated weight gain. Methods:Adults with a ≥10% increase in body weight while on an INSTI (± tenofovir alafenamide) regimen and HIV RNA <50 copies/mL were switched to DOR/3TC/TDF for 12 months. Weight, waist circumference, and routine bloodwork were measured at baseline and every 12 weeks. Total body fat (DXA scan) and body image/self-esteem (B-WISE, modified Fat Redistribution and Metabolic Change in HIV questionnaires) were assessed at baseline and week 48. The target enrolment was 25 participants. Results:Between September 2021 and September 2023, four participants were enrolled, with the results available for three women (Black, age 51/56/70 years, BMI 45.3/33.9/30.8 kg/m2, 56%/45.7%/50% total body fat, with a 10%/13%/18% weight increase on the INSTI-regimen for 5.5/4.25/4.5 years). At 12 months, reductions in weight (0%/-7.5%/-6.7%), BMI (0/-2.6/-2 kg/m2), waist circumference (-0.8/-1.1/+1 cm), total body fat (-1.5%/-2.9%/-3.5%), blood pressure, fasting glucose, and lipids were observed. Body image/self-esteem improved; all maintained HIV RNA <50 copies/mL with no proteinuria/significant eGFR change. The study was closed due to futility in attaining timely target enrolment. Conclusions:Two out of three Black women with a ≥10% INSTI-associated increase in body weight had weight loss of >5% after switching to DOR/3TC/TDF for 48 weeks. All three participants experienced small improvements in waist circumference, body fat, and metabolism, and all reported improvements in body image/self-esteem. Pandemic challenges significantly impacted the ability to enrol participants.

INTRODUCTION:Advances in human immunodeficiency virus (HIV) care have increased life expectancy, leading to more older adults living with HIV. This study examines older adults' perspectives on geriatric healthcare needs. METHODS:A community-based qualitative study in Ontario, Canada, recruited some adults aged 50+ years living with HIV through quota and purposive sampling. Quota sampling was used to include individuals of different ages, genders and ethno-racial backgrounds to capture a range of experiences. Data were collected via semi-structured interviews and focus groups, analyzed using the Qualitative Analysis Guide of Leuven. RESULTS:Participants included interviewees (n = 14) and focus group attendees (n = 12). Four themes emerged: (1) lack of knowledge and access to geriatric care, highlighting service challenges; (2) healthcare providers' understanding of HIV and ageing, with stigma concerns; (3) role of social support networks for emotional/practical support; and (4) requirements for improved geriatric care, advocating provider education and greater social care access. CONCLUSIONS:Gaps in geriatric care for older adults with HIV highlight stigma, access issues and the need for education, virtual care and tailored, inclusive healthcare solutions.

Background The intersection of aging and HIV presents unique challenges in healthcare, with older adults living with HIV experiencing compounded health issues. Advances in technology, including digital health tools, offer opportunities to improve self-management and care delivery. However, older adults living with HIV face barriers in adopting these digital health tools due to socio-cultural factors and technological challenges. Objective This study explores the factors influencing the adoption of digital health technologies for HIV management among older adults, aiming to identify strategies to improve accessibility and effectiveness of these tools. Methods A qualitative descriptive study using interviews was conducted within a larger research program on virtual care for socio-culturally diverse older adults. Data were analyzed using the Theoretical Domains Framework (TDF) to identify barriers and facilitators to technology adoption. Results Fourteen older adults living with HIV (mean age 58.7, SD 6.5) participated in the study. Key themes included self-management, perceived usefulness, and ease of use, with older adults living with HIV using technology for health tracking and symptom management. Barriers such as affordability, linguistic diversity, and complex user interfaces were identified, along with concerns about privacy and stigma. Facilitators included peer influence, perceived utility of tools, and ease of navigation. Participants emphasized the importance of transparency in consent processes and the need for technology to accommodate cognitive and sensory impairments. Conclusion This study highlights the need for tailored digital health interventions that address the unique challenges of older adults living with HIV. Future technologies should prioritize user-friendly interfaces, accessibility, and clear consent processes to enhance adoption and engagement.

BACKGROUND:Tecovirimat is an antiviral drug that was used compassionately for treating mpox in high-income settings during the 2022 global outbreak. Randomized controlled trials of its efficacy have not yet been completed. OBJECTIVES:To describe medication adherence, tolerability and clinical outcomes of adults receiving open-label tecovirimat for mpox infection. METHODS:We conducted a prospective observational study and a retrospective case series of adults with mpox cared for at three academic hospitals in Toronto, Canada, between May and August 2022. We present a descriptive analysis of those prescribed oral tecovirimat 600 mg twice daily for 14 days for the management of severe manifestations. RESULTS:Of 69 consenting participants, all were cisgender men, of whom 60 (87%) identified as gay, and 6 (9%) as bisexual. Nearly half (46%) were living with HIV, with a median (IQR) CD4 count of 468 (328-678) cells/mm3, among whom plasma HIV RNA was <20 copies/mL in 29 (91%) participants. One-third (33%) of participants received tecovirimat during the course of their illness. All participants experienced a decline in number of symptoms over time, but three treated participants initially experienced worsening symptoms despite therapy. Self-reported adherence to tecovirimat was excellent and tolerability was good. CONCLUSIONS:Our experience prescribing tecovirimat for mpox suggests it is safe and well tolerated, but the evolution of symptoms in some tecovirimat-treated patients underscores the ongoing uncertainty regarding its efficacy. In the context of considerable community demand for the drug, efforts should be made to connect mpox patients to rigorous randomized controlled trials, given this ongoing clinical equipoise.

BACKGROUND:Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections increase the risk of hepatic steatosis (HS), which in turn contribute to the severity and progression of liver disease. Direct-acting antivirals (DAAs) can cure HCV but whether they reduce HS is unclear. METHODS:HS was assessed using the controlled attenuation parameter (CAP) and the Hepatic Steatosis Index (HSI) in participants coinfected with HIV and HCV from the Canadian Coinfection Cohort. Changes in HS, before, during, and after successful DAA treatment were estimated using generalized additive mixed models, adjusted for covariates measured prior to treatment (age, sex, duration of HCV infection, body mass index, diabetes, prior exposure to dideoxynucleosides, and hazardous drinking). RESULTS:In total, 431 participants with at least 1 measure of CAP or HSI before treatment were included. CAP steadily increased over time: adjusted annual slope 3.3 dB/m (95% credible interval [CrI], 1.6-4.9) before, and 3.9 dB/m (95% CrI, 1.9-5.9) after DAA treatment, irrespective of pretreatment CAP. In contrast, HSI changed little over time: annual slope 0.2 (95% CrI, -0.1 to 0.5) before and 0.2 (95% CrI, -0.1 to 0.5) after, but demonstrated a marked reduction during treatment -4.5 (95% CrI, -5.9 to -3.1). CONCLUSIONS:When assessed by CAP, HS was unaffected by DAA treatment and steadily increased over time. In contrast, HSI did not appear to reflect changes in HS, with the decrease during treatment likely related to resolution of hepatic inflammation. Ongoing HS may pose a risk for liver disease in coinfected people cured of HCV.

Background:Drug poisoning (overdose) is a public health crisis, particularly among people living with HIV and hepatitis C (HCV) co-infection. Identifying potential predictors of drug poisoning could help decrease drug-related deaths. Methods:Data from the Canadian Co-infection Cohort were used to predict death due to drug poisoning within 6 months of a cohort visit. Participants were eligible for analysis if they ever reported drug use. Supervised machine learning (stratified random forest with undersampling to account for imbalanced data) was used to develop a classification algorithm using 40 sociodemographic, behavioural, and clinical variables. Predictors were ranked in order of importance, and odds ratios and 95% confidence intervals (CIs) were generated using a generalized estimating equation regression. Results:Of 2,175 study participants, 1,998 met the eligibility criteria. There were 94 drug poisoning deaths, 53 within 6 months of a last visit. When applied to the entire sample, the model had an area under the curve (AUC) of 0.9965 (95% CI, 0.9941-0.9988). However, the false-positive rate was high, resulting in a poor positive predictive value (1.5%). Our model did not generalize well out of sample (AUC 0.6, 95% CI 0.54-0.68). The top important variables were addiction therapy (6 months), history of sexually transmitted infection, smoking (6 months), ever being on prescription opioids, and non-injection opioid use (6 months). However, no predictor was strong. Conclusions:Despite rich data, our model was not able to accurately predict drug poisoning deaths. Larger datasets and information about changing drug markets could help improve future prediction efforts.

Background Females and persons of Black race are often underrepresented in clinical trials. This post hoc analysis of data from three phase 3 studies evaluated the efficacy and safety of doravirine (DOR) by sex and race in adults living with HIV-1. Methods DRIVE-FORWARD and DRIVE-AHEAD open-label extensions were pooled; participants randomized to first-line DOR-based regimen continued from week (W) 96 to W192 (DOR-continued group) and participants randomized to comparators switched to DOR from W96 to W192 (DOR-switch group). In DRIVE-SHIFT, virologically suppressed adults were randomized to switch to a DOR-based regimen on day 1 (immediate-switch group) or W24 (delayed-switch group) and continued through W144. Results are reported by sex assigned at birth (male vs female) and race (Black vs non-Black). Results Across trials, female and Black participants each represented <20% of study populations. After continuing or switching to DOR, percentages of participants with HIV-1 RNA <50 copies/mL were comparable between sex and race subgroups. Mean changes in CD4+ T-cell counts and proportions of participants with drug-related adverse events or serious adverse events were generally similar between subgroups. In DRIVE-SHIFT, higher rates of nontreatment-related discontinuations were observed within Black versus non-Black subgroups. Differences in median weight change were generally larger between race subgroups than sex subgroups, although interquartile ranges were wide for all. Conclusions Participants who continued or switched to DOR generally had comparable efficacy and safety outcomes across sex and race subgroups. However, the sample size was limited. Future studies should ensure greater diversity when investigating factors leading to outcome disparities. ClinicalTrials.gov: NCT02275780, NCT02403674, NCT02397096.

BACKGROUND:Definitions of virological failure and treatment discontinuation for long-acting injectable (LAI) cabotegravir and rilpivirine antiretroviral therapy are inconsistent in clinical practice and observational studies, which complicates interpretation and implementation of findings. The CONSENSUS-LAI study aimed to establish consistent definitions of virological failure and treatment discontinuation to enhance evidence transferability and support optimal clinical outcomes. METHODS:The study had two phases. Phase 1 was an international online survey exploring existing definitions of virological and treatment discontinuation, conducted between April 25 and July 1, 2024. Eligible participants were health-care professionals working in infectious disease or sexual health services who had provided care to at least ten people living with HIV in the past 6 months, had prescribed LAI cabotegravir and rilpivirine in clinical trials or clinical practice, and were able to give informed consent. Participants were recruited via social media and mailing lists of medical specialist societies. Phase 2 was a Delphi process, in which a panel of experts, selected to ensure representation from all six WHO regions, scored leading definitions from phase 1 on a 9-point Likert scale. The proposed definitions were scored according to four validity criteria: clarity, usability in the expert's setting, appropriateness across clinical purposes, and applicability across relevant population groups. Revisions were suggested in iterative rounds until consensus was reached. Consensus was predefined as at least 75% of experts agreeing or strongly agreeing (scores 7-9) with the validity criteria. FINDINGS:386 LAI cabotegravir and rilpivirine prescribers across 28 countries completed the survey, revealing 15 definitions for virological failure on LAI cabotegravir and rilpivirine and nine for treatment discontinuation. 52 experts participated in the Delphi process. Consensus agreement on both definitions was reached after two rounds for all validity criteria. For virological failure, the consensus definition was as follows: (a) viral load 200 copies or more per mL or more on two occasions 2-4 weeks apart, or (b) a single viral load of more than 1000 copies per mL, and/or (c) emergent resistance, in the context of timely injections and prior suppression of less than 200 copies per mL, OR (d) unable to suppress viral load to less than 200 copies per mL on continuous therapy. For treatment discontinuation the consensus definition was as follows: people on LAI cabotegravir and rilpivirine who have missed two consecutive injections and have not taken oral bridging in the interim, irrespective of reason for discontinuation. INTERPRETATION:The consensus definitions provide a foundation for aligning practice and evaluating patient outcomes. Further validation of the viral load threshold for virological failure and the optimal viral load retesting window is required. FUNDING:ViiV Healthcare.

BACKGROUND:Mpox disease, caused by the monkeypox virus (MPXV), remains a global health concern with nearly half of all cases occurring among individuals with human immunodeficiency virus (HIV). While recent studies have advanced our understanding of poxvirus pathogenesis, the molecular effects of mpox and HIV coinfection are still poorly understood. This study uses dual RNA sequencing (RNA-seq) to characterize host and viral gene expression in skin lesion swabs from people with mpox, including individuals with and without HIV. METHODS:Our cohort included 19 participants with confirmed MPXV infection, with 53 total skin lesion swabs collected during the early (7-13 days post-symptom onset) and late (15-21 days post-symptom onset) stages of mpox disease. RNA-seq was used to assess both host and MPXV gene expression over time in participants with and without HIV. RESULTS:HIV-positive participants showed upregulation of MPXV genes involved in immune evasion and viral replication. Conversely, host immune pathways, such as interferon signaling, apoptosis, and chemokine recruitment, were downregulated in participants with HIV. Pathway enrichment analysis revealed dysregulated immune signaling and autophagy, key processes for viral clearance. These findings suggest that HIV-related immunosuppression may enhance MPXV replication and prolong disease. CONCLUSIONS:This study highlights the use of dual RNA-seq in uncovering molecular interactions between host and virus during mpox infections. Our findings offer insights into how HIV coinfection may alter MPXV pathogenesis, with implications for treatment strategies and disease management in immunocompromised populations.

BackgroundOlder adults living with HIV face challenges accessing regular geriatric care, and while virtual care services could offer a solution, they may come with limitations. ObjectiveThis study aimed to co-design a culturally appropriate virtual care model tailored to older adults’ needs using the experience-based co-design methodology. MethodsWe used a qualitative, experience-based co-design approach with 19 older adults living with HIV. The process involved 3 phases: identifying needs through interviews and questionnaires, codeveloping a care model prototype through focus groups and a workshop, and refining the model using feedback from a world café format. Data were analyzed using thematic content analysis. ResultsThe co-design process led to a virtual care model prototype that directly addressed participants’ key needs. These included personalized communication methods, simplified technology interfaces for easier access, and culturally responsive care practices. Participants emphasized the importance of privacy in virtual consultations, flexible scheduling to accommodate health fluctuations, and ongoing support for managing both HIV and aging-related conditions. Their feedback shaped a model designed to bridge service gaps, offering a more inclusive, accessible, and patient-centered approach to virtual geriatric care. ConclusionsThis study co-designed a potential virtual geriatric care model grounded in the experiences of older adults living with HIV. By integrating participants’ insights throughout the design process, the model offers a promising approach to improving care for this vulnerable population. Future directions for research to test this model are proposed.