Lenacapavir (LEN) is a highly potent, long-acting, first-in-class inhibitor of HIV-1 capsid protein for the treatment of HIV-1 infection in adults with multidrug resistance (MDR) in combination with other antiretrovirals.

CAPELLA is an ongoing, phase 2/3 study in heavily treatment-experienced people with HIV-1 with multidrug-resistance. Participants received oral LEN for loading followed by subcutaneous LEN Q6M in addition to an optimized background regimen (OBR). The protocol was amended after week 52 to allow longer follow up; we report W104 results.

Of 72 participants enrolled (36 in each cohort), 25% were female, , median age was 52 years, 64% had CD4 200 cells/µL, and 46% had HIV-1 resistant to all 4 major classes (NRTI, NNRTI, PI, INSTI). One participant (of 72) decided not to continue in the post-W52 extension. At W104, 62% (44/71) had HIV-1 RNA 50 c/mL via FDA Snapshot algorithm, and 14% (10/71) had HIV-1 RNA 50 c/mL; 24% discontinued for reasons other than lack of efficacy (13/71) or had missing data but were on study drug (4/71). When analyzed as missing=excluded, 81% (44/54) had HIV-1 RNA 50 c/mL. CD4 count increased by a median 97 cells/µL (Q1 to Q3: 18 to 224) Fourteen participants had emergent LEN resistance, 6 of whom subsequently suppressed while continuing LEN. The median (Q1–Q3) duration of follow-up on LEN was 125 (111–140) weeks. One participant discontinued due to injection site nodule at W52 (Grade 1, previously reported); no participant discontinued due to an AE after W52. Most common AEs (excluding injection site reactions [ISRs] and COVID-19) were diarrhea and nausea (19% each, +5% each since W52, respectively). LEN-related ISRs were mostly mild-to-moderate.

In people with MDR HIV-1 and limited treatment options, LEN in combination with an OBR was well tolerated and maintained virologic suppression at W104.

Background: Rates of trauma and/or violence in the lives of women with HIV are high and can have detrimental health and social impacts. To inform the design of trauma/violence healing programs, we surveyed women and gender diverse people to gather insights on the optimal design, delivery, and essential components for effective programs.

Methods: Informed by intersectionality and community-based research approaches, we developed a mixed methods, strengths-based survey. Women and gender diverse people with HIV in British Columbia and Ontario were recruited through clinics, health organizations, and by community research associates (CRAs; women with HIV trained in research). CRAs administered the surveys. Qualitative responses were typed or recorded and transcribed (according to participant preference). In this presentation, we share our preliminary descriptive statistics and content analysis.

Results: 115 women and gender diverse people (82.6% cis, 17.4% gender diverse) participated (median age=49, range=20-81). 77% of participants reported childhood trauma and 96.5% adulthood trauma. Few participants (12.1%) always received the professional support they desired. The top activities participants accessed and would do again for healing included: exercise (94.8%); nature activities (84.3%); art, crafting, and/or art therapy (77.4%); music/music therapy (77.4%); and religious/spiritual engagement (73.9%). Participants felt it was important for programs to: be cost-free (85%); include food (75.7%) and transportation (71.3%); be population-specific [e.g., only women (56.5%) or people with HIV (67.0%)]; involve loved ones (68.7%); and be peer-led or have peer-involvement (80.9%).

Conclusions: Most participants had experienced both childhood trauma (events that could be classified as adverse childhood events; ACE) and adulthood trauma. Professional support options were often inaccessible or unhelpful. Therefore, increased accessibility for diverse TVAC programming that supports healing is urgently needed. Our findings offer crucial insights to shape meaningful trauma/violence healing programs, including the necessary inclusion of women and gender diverse people in their design.

Background
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 (MLWH). However, models for rapid B/F/TAF initiation are not well studied among MLWH, and there is limited understanding of how social determinants of health (SDH) may affect HIV-related health outcomes for migrants enrolled in such care models.

Methods
Within a 96-week pilot feasibility prospective cohort study at a multidisciplinary HIV clinic, participants received B/F/TAF for free and rapidly following care linkage. The effect 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 B/F/TAF initiation and HIV viral undetectability were calculated from care linkage via survival analyses

Results
Thirty-five migrants were enrolled in this study. Median time to B/F/TAF initiation and HIV undetectability was 5 (range: 0-50) and 57 days (range: 5-365), respectively. Those who took longer to initiate B/F/TAF: were less than 35 in age (p-value = 0.002, 95% CI = -1.98 to -0.44); identified as heterosexual (p-value = <0.001, 95% CI = 0.90 to 2.74); had less than university-level education (p-value = 0.003, 95% CI = 0.43 to 2.09); or were unemployed (p-value = 0.021, 95% CI = -1.69 to -0.11). No factor was found to significantly affect participants’ time to HIV viral undetectability.

Conclusions
Despite cost-covered B/F/TAF, several SDH were linked to delays in ART initiation. However, once initiated and engaged, MLWH were able to reach HIV undetectability efficiently. Findings provide preliminary support for adopting this care model with MLWH, but concurrently suggest that SDH and other covariates should be considered when designing clinical interventions for more equitable outcomes.

Background:
In London, Ontario, people living with HIV who experience housing instability and have substance use disorders have challenges with daily antiretroviral medication adherence. Monthly injectable antiretroviral medication offers a possible solution; however, safe delivery of this medication requires a comprehensive care program. Design thinking methodology provides a framework to create an innovative model of care that centers this population’s needs and utilizes the local resources available in this setting.

Aim: We describe the design thinking-informed process used for the inspiration and ideation phase of care program design.

Methods:
During the inspiration and ideation phase, we engaged stakeholders to build off of pre-existing care structures and brainstorm new care pathways. In order to build empathy in clinical care design, interviews for end-users were performed with participants enrolled in our pre-existing HIV care programs. Interviews were transcribed and analyzed using thematic analysis.

Results:
Engaged stakeholders include primary care serving vulnerable patients, physicians and outreach workers from the local public health unit, an outpatient pharmacy, psychiatry outpatient teams (ACT), and the local jail.
In total, eleven interviews were conducted with participants enrolled in our pre-existing HIV care program. Themes generated include dissatisfaction with their current daily antiretroviral regimen, while reasons cited include forgetting to take or losing their medications, having them stolen, and that picking up their medications disrupts their lives. Participants were interested in enrolling in a program (Likert Scale: mean 4/5), though anticipated barriers include attending regular appointments, not having a phone, or concurrent competing social factors including lack of housing.

Conclusions:
Design thinking methodology was useful in the early phases in the creation of a care program to safely deliver injectable HIV medication to vulnerable patients. We engaged a diverse set of stakeholders and incorporated the current preferences of our patient population.

Background: To address the HIV pandemic, a concerted effort is needed to include vulnerable inner-city residents, many of whom are active drug users, disengaged from care, and facing issues such as housing and financial insecurities. We have evaluated a new model of HIV care using our community pop-up clinic (CPC) as a strategy to identify HIV-infected individuals to engage them in care and maintain them on antiretroviral therapy.
Methods: Weekly events are conducted at places of residence in Vancouver’s inner city. Point-of- care testing for HCV and HIV are completed (with phlebotomy performed on site), along with ascertainment of prior HCV or HIV infection status. All individuals in whom this is indicated are then offered access to antiretroviral therapy delivered within a multidisciplinary program with adherence support.
Results: From 01/21 to 11/23, we conducted 125 CPCs (3.5 events/month) evaluating 2111 individuals, 68 (3.2%) of whom tested positive for HIV antibodies, all previously diagnosed with HIV infection and lost to follow up. Of the 68, 45 (66.2%) showed active HCV co-infection. Among HIV-infected subjects, we note median age 50 (25-66) years, 24 (35.3%) female, 11(16.2%) indigenous, and 26 (38.3%) with unstable housing, 28 (41.2%) experiencing recent incarceration, and 26 (38.2%) were active drug users, 25 of whom had a significant opioid overdose in the previous 6 months. Of 68, 45 (66.2%) engaged in long-term care at our center and continued with antiretroviral therapy.
Conclusions: Although we have made significant progress in the control of the HIV pandemic in British Columbia, many inner-city residents have disengaged from care and discontinued antiretroviral therapy. To control disease progression and transmission in this priority population, there is an urgent need to develop and evaluate interventions such as our CPC program to optimize our approach to the diagnosis and treatment of HIV infection in Canada.

Background: Continuity of care (CoC) has been shown to decrease adverse clinical outcomes and is critical to improving healthcare engagement for people living with HIV (PLWH). This study will characterize and assess correlates with CoC among a cohort of PLWH across BC.

Methods: We recruited 644 PLWH aged ≥19 years in BC between January 2016-September 2018 into the STOP HIV/AIDS Program Evaluation (SHAPE) study using purposive sampling across BC. We collected data regarding socio-demographics, health behaviours, and medical history through interviewer-administered surveys. In this analysis, we characterize HIV-related CoC using a validated scale (HIV Engagement in and Continuity of Care Scale) and utilize a linear regression model to determine factors associated with higher reported CoC scores in the cohort.

Results: Of the 640 PLWH in the SHAPE study who completed the CoC scale, 459 (71.7%) identified as cis-men and the median age was 50 years old (Q1-Q3: 42, 56). Median CoC scores were higher among cis-men when compared to cis-women or Trans/non-binary/2S participants (138 vs 134 vs 132, respectively, p=0.044) and among participants without a history of injection drug use when compared to those reporting use ever or in the past 12 months (141 vs 135 vs 129, p<0.001). In the regression model, higher CoC scores were negatively associated with homelessness in the past 12 months or lifetime homelessness (-6.89, 95% CI: -10.55- -3.23; -4.00, 95%CI: -6.63- -1.36, respectively) compared to those never experienced homelessness and higher everyday discrimination scores (-0.52, 95% CI: -0.63- -0.40). Comparatively, later era of HIV diagnoses (from 2010 onwards) was positively associated with higher CoC scores (5.60, 95%CI: 1.25- 9.95) compared to those diagnosed before 1996.

Conclusions: CoC for PLWH may vary significantly and enhanced supports for long-term survivors of HIV and those facing structural inequities, such as homelessness, may be important to improve CoC.

Background: People with HIV are at higher risk of infection-related cancers (e.g., human papillomavirus-related cervical and anal cancers) than people without HIV. The objective of this study was to explore the role of CD4 measures as immune function indicators on infection-related and infection-unrelated cancer risk.

Methods: Participants of the Ontario HIV Treatment Network Cohort Study linked to cancer registry data at ICES (formerly the Institute for Clinical Evaluative Sciences) were included in the study. Incident cancers were ascertained from January 1, 1997 to December 31, 2020 and grouped into infection-related and -unrelated cancers. Competing risk time to event analysis was used to obtain adjusted hazard ratios (aHR) and 95% confidence intervals (CIs). Separate models were conducted for the associations between baseline CD4, nadir, time-updated or current CD4 and CD4:CD8, and cancer incidence rates, stratified by cancer grouping.

Results: 4,771 people with HIV contributed 59,111 person-years of observation. Of the 549 cancers identified, 48.5% were infection-related cancers. The most diagnosed cancers were non-Hodgkin lymphoma, anal, and lung cancer, as well as prostate among males and breast cancer among females. Low baseline CD4 (<200 cells/µL) (aHR 2.08 [95% CI 1.38-3.13], nadir (<200 cells/µL) (aHR 2.01 [95% CI 1.49-2.71]), current CD4:CD8 ratio (<0.4) (aHR 2.02 [95% CI 1.08-3.79]), and current CD4 (aHR 3.52 [95% CI 2.36-5.24]) were associated with an increased hazard rate of infection-related cancer when compared to CD4 counts of at least 500 cells/µL. No associations were observed for infection-unrelated cancers.

Conclusions: Low CD4 counts were associated with an increased risk of infection-related cancer among people with HIV, irrespective of the CD measure used. Early diagnosis and linkage to care and high antiretroviral therapy uptake may improve immune function and could add to other prevention strategies such as screening and vaccine uptake.

Background: Therapeutic drug monitoring (TDM) of integrase inhibitors (INIs) is often conducted in the pediatric population but it is unclear if this is needed.
Methods: Retrospective study of data from the Québec Antiretroviral TDM program. Children and adolescents (> 6 weeks of life to < 18 years old) living with HIV who had at least one INI TDM between January 1st 2011 and March 31st 2023 were included. Concentrations at the end of the dosing interval (Ctrough) were extrapolated. Ctrough were therapeutic if: bictegravir ≥0.84 mg/L, dolutegravir ≥0.32 mg/L, elvitegravir ≥0.13 mg/L, raltegravir ≥0.02 mg/L. Dolutegravir Ctrough was considered supratherapeutic if ≥1.47 mg/L. Intersubject coefficient of variation (CV%) for each INI was calculated. Mean Ctroughs were compared for patients achieving or not a viral load <50 copies/mL using a T test.
Results: Overall, 107 subjects were included (per INI (# subjects/# samples): bictegravir 16/35; dolutegravir 56/285; elvitegravir 32/150; raltegravir 50/383). Mean (SD; range) age 10.3 (4.7; 0.2-17.8) years, 57% female, viral load <50 copies/mL 79.2% (range over study period: undetectable-6.85 log₁₀), mean (SD) CD4+ 590(245). Ctroughs were above virologic efficacy thresholds for 96.8% (bictegravir), 94.5% (dolutegravir), 79.2% (elvitegravir) and 86.4% (raltegravir) of samples. Dolutegravir Ctrough was supratherapeutic for 68.9% of samples. For subjects 6 weeks-<12 years old, intersubject CV% were 69.9% (bictegravir), 50.9% (dolutegravir), 111.3% (elvitegravir), 172.0% (raltegravir). For subjects 12-<18 years old, these results were 63.8%, 52.4%, 94.1%, 112.7%, respectively. Overall, subjects 12-<18 years old had a higher proportion (9.6%) of undetectable Ctrough as compared to younger subjects (5.4%). Mean raltegravir Ctrough was lower in subjects with a viral load ≥ 50 copies/mL (p=0.08).
Conclusions: Most INI Ctroughs were above the efficacy thresholds. Routine TDM of INIs is not recommended in this population. Pediatric patients receiving dolutegravir should be monitored for a possible increased risk of toxicity.