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Clinical Sciences Oral Abstract Session #2

Tracks
Track 2
Friday, April 26, 2024
15:00 - 17:00
Salon J

Overview

Sciences cliniques séances de présentation orale d’abrégés #2


Speaker

Lane Buchanan
PhD Candidate
Western University

Bacteria Associated with HIV Seroconversion and Immune Cells Alter Epithelial Junctions and Increase Keratinocyte Proliferation

Abstract

Background: Specific anaerobic taxa within the penile microbiome are associated with HIV-1 seroconversion, inflammation, and a higher density of HIV-susceptible immune cells in the inner foreskin. The effect of these bacteria (referred to as BASIC species) on epithelial barrier integrity, however, has not been described.

Methods: Using foreskin tissues and penile swabs from n=116 adult HIV-negative males undergoing voluntary medical male circumcision in Entebbe, Uganda, we assessed the relationship between BASIC species abundance (16S rRNA gene analysis) and metrics of foreskin epithelial integrity including epithelial junction protein expression, epithelial thickness, and cellular proliferation (quantitative immunofluorescence).

Results: Tissues from participants with high BASIC species density (n=21) showed reduced E-cadherin (59.22 vs. 63.31% area, p<0.05) and claudin-1 (56.92 vs. 62.43% area, p<0.05) expression, and increased desmoglein-1 (64.58 vs. 58.17% area, p<0.05) expression compared to participants without BASIC species (n=25). Reduced tissue E-cadherin was associated with increased soluble E-cadherin on the foreskin surface (ρ=-0.26, p=0.005), suggesting proteolytic cleavage. BASIC species were associated with increased thickness of the nucleated cell layers (77.10 vs. 62.07µm, p<0.001) and increased keratinocyte proliferation (15.19 vs. 6.64% Ki-67+ cells, p<0.001), but no difference in stratum corneum (keratin) thickness.

Discussion: These results indicate that BASIC species may enhance HIV susceptibility in uncircumcised males through alterations to foreskin epithelial structure, in addition to previously described effects on penile immunology.


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James Pollock
Graduate Student
University Of Toronto

Forced Vaginal Sex Is Associated with Short-Term Genital Inflammation That May Enhance HIV Susceptibility for at Least Seven Days

Abstract

Background: HIV risk is higher among women who have been exposed to forced vaginal sex, both in the short- and long-term, and several epidemiological pathways exist between forced sex and HIV infection. However, genital inflammation is a key biological determinant of HIV susceptibility, and might be induced by epithelial trauma in this context. Here we explore cervicovaginal inflammation and epithelial barrier disruption as potential biological mediators of HIV risk after forced vaginal sex.

Methods: Levels of proinflammatory cytokines and soluble E-cadherin (sE-cad), a biomarker of epithelial barrier disruption, were measured in cervicovaginal secretion samples from a prospective cohort of 746 HIV-uninfected female sex workers (FSWs) in Nairobi, Kenya by multiplex immunoassay. Sociodemographic factors were compared between participants who were physically forced to have sex in the 7 days preceding the study visit and those not recently exposed to forced sex. Genital inflammation was defined using a composite score of inflammatory cytokines previously associated with HIV acquisition. The presence of inflammation was compared between groups using mixed-effects logistic regression models to control for potential confounders.

Results: 44 (6%) of 746 participants reported forced sex during the prior week at baseline, and 42 (95%) of these women continued to have sex with other clients during this time (median = 4 clients in the past week). Recent forced sex was strongly associated with increased genital inflammation (aOR = 2.74; 95% CI: 1.33 – 5.68; p < 0.01) independent of previously-defined biological confounders such as bacterial vaginosis. There was no difference in sE-cad concentrations (p = 0.56).

Conclusions: Cervicovaginal inflammation is increased for at least a week in FSWs exposed to forced vaginal sex, who have no option but to continue sex work during this time. This has important implications for HIV prevention programs providing care to women experiencing gender-based violence and survival sex.


Maryam Habib
Research Assistant II
MAP Centre for Urban Health Solutions, St. Michael's Hospital Unity Health Toronto

Systematic Review of PEP Clinical Trials & Cohort Studies to Inform Updated Canadian Guidelines

Abstract

Background: We conducted a systematic review of PEP clinical trials and cohort studies on HIV post-exposure prophylaxis (PEP) to inform forthcoming updated Canadian guidelines.

Methods: We searched Medline and Embase (July 2017-September 2023) for studies reporting on: PEP completion, adverse events (AEs) leading to discontinuation, and/or HIV acquisition. Two reviewers independently screened abstracts and publications and extracted data from eligible articles.

Results: Of 5451 references, 604 duplicates were removed, 4847 abstracts screened, 78 full-text articles reviewed, and 22 eligible included. Median study size: 156 (range=30-29060) participants. Studies included 9 (41%) retrospective cohorts, 8 (36%) prospective cohorts, 3 (14%) non-randomized trials and 2 (9%) randomized trials. The studies examined heterogeneous populations (n=14, 64%), healthcare workers (n=4, 14%), gay, bisexual, and other men who have sex with men (n=2, 9%) and sexual assault survivors (n=2, 9%). Most studies were conducted in Europe (n=12, 55%) with remainder in Asia, Africa, North America, and Australia. Regimens included TDF/FTC/DTG (n=5, 23%), TDF/FTC/EVG/c (n=5, 23%), TAF/FTC/EVG/c (n=4, 18%), TDF/FTC/RPV (n=2, 9%), TAF/FTC/BIC (n=2, 9%), TDF/FTC/MVC (n=1, 5%), TDF/FTC/RAL(n=1, 5%) and one (5%) with the injectable fusion inhibitor albuvirtide; several studies included multiple regimens (n=11, 50%). Amongst studies examining PEP completion rates (n=19, 86%), cumulative completion rate was 78% (18,094/23,335) and appeared highest for BIC/FTC/TAF at 95% (155/164). PEP tolerability was good, with few discontinuations due to adverse events; where data were available this was 5/130 (3.8%) for TAF/FTC/EVG/c, 8/219(3.6%) for TDF/FTC/EVG/c, 4/148 (2.7%) for TDF/FTC/RPV, 1/38(2.6%) for TDF/FTC/LPV/r, 2/143(1.4%) for TDF/FTC/RAL and 9/255(1.9%) for TDF/FTC/DOR. HIV seroconversions were extremely rare regardless of regimen (n=7/10784), and often related to premature PEP discontinuation or repeated exposures.

Conclusions: Multiple PEP regimens have been associated with high completion, good tolerability, and rare seroconversion and warrant consideration in forthcoming Canadian guidelines.


Monica Rudd
Research Assistant
Options Lab - St Michael's Hospital

Reported Side Effects and Adherence of Daily HIV PrEP Users in Ontario, Canada: An Analysis of the Ontario PrEP Cohort Study

Abstract

Side effects are a common concern of potential HIV pre-exposure prophylaxis (PrEP) users, and may cause current users to miss doses.

We examined the relationship between reported side effects and adherence in the Ontario PrEP Cohort Study (ON-PrEP). Participants completed questionnaires assessing the presence and severity of five side effect categories (nausea, diarrhea, headache, abdominal pain, and “other”) and adherence to daily PrEP (any missed doses in the previous four days). We characterized users experiencing side effects, and assessed for trends in reported side effects with duration of PrEP use. We then performed mixed-effects logistic regression testing for differences in odds of reporting perfect adherence as functions of three side effects measures (any side effects, number of categories reported, and sum of severity ratings).

Of 600 participants, 175 (29%) ever reported experiencing any side effects: most commonly diarrhea (7.5% of study visits), followed by abdominal pain (5.3%), headache (5.1%), nausea (3.9%), and “other” (2.6%), and most were of mild severity. The odds of reporting any side effects decreased by a factor of 0.44 (95% CI 0.25-0.80) with each additional year of PrEP use, however one in ten participants still reported side effects at visits after one year. Lower incomes (p=0.01), identifying as bisexual (p=0.04), and expressing baseline concern about side effects (p<0.001) were significantly associated with ever reporting side effects. Odds of reporting perfect adherence were 0.48 (0.28-0.83) times lower for participants reporting any side effects, 0.67 (0.51-0.89) times lower per additional side effect category reported, and 0.78 (0.65-0.97) times lower for each incremental increase in side effect severity. We found some evidence that these relationships were stronger for participants who had been taking PrEP longer.

Clinicians should make efforts to ascertain patients’ experience of side effects and consider risk counseling and alternative regimens to promote adherence among these users.


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Tasha Ramsey
Clinical Lead
Nova Scotia Health

Pharmacist Prescribing for Human Immunodeficiency Virus Pre-Exposure Prophylaxis in Nova Scotia (PrEP-Rx Study)

Abstract

Background: Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is a powerful preventative strategy to reduce HIV transmission and promote health. Individuals on PrEP are regularly screened for HIV, other sexually transmitted infections (STIs), and adverse effects which promote routine connections with healthcare. Despite significant personal and public health benefits, access to HIV PrEP prescribers in the context of a primary healthcare provider shortage is a challenge. In Nova Scotia (NS), some pharmacists have expressed a willingness to address this care gap, and target users have shown interest in pharmacist-prescribed HIV PrEP. The objective of PrEP-Rx is to evaluate the feasibility and acceptability of pharmacist prescribing for HIV PrEP.

Methods: Participating pharmacists in NS were enabled to prescribe once-daily HIV PrEP (tenofovir disoproxil fumarate and emtricitabine) using a research protocol. Participants had appointments with a pharmacist for eligibility assessment, initial prescribing, follow-up, and referral appointments. Pharmacists provided participants with laboratory requisitions for bloodwork and STI monitoring and verified the results before prescribing or releasing medication refills. Participants were invited to complete an electronic questionnaire to collect demographic and satisfaction data. Descriptive statistics were used to analyze results.

Results: Ten pharmacies participated in an HIV PrEP prescribing demonstration project from February to October 2023. All 45 participants who attended the eligibility appointment met HIV PrEP criteria based on sexual risk factors; 51% of participants had never used PrEP before. All participants remained HIV-negative while enrolled in the study. Four co-infections, hepatitis B, syphilis, chlamydia, and gonorrhea, were identified through pharmacist monitoring and linked to care. All respondents believed PrEP prescribing should always be available in pharmacies, and 97% felt comfortable seeing the pharmacist and found the pharmacy accessible.

Conclusions: Pharmacists prescribing for HIV PrEP was successfully piloted in community pharmacies in NS. Participants reported positive experiences with the prescribing pharmacist.


Stanley Onyegbule
St. Michael's Hospital, Unity Health Toronto

Systematic Review of PrEP Clinical Trials & Cohort Studies to Inform Updated Canadian Guidelines

Abstract

Background: We conducted a systematic review of clinical trials and cohort studies on HIV pre-exposure prophylaxis (PrEP) to inform forthcoming updated Canadian guidelines.

Methods: Using PRISMA, we searched Medline and Embase (July 2017-July 2022) for studies reporting on at least one of; HIV acquisition, tolerability, toxicity, mental health benefits, drug resistance, and perinatal outcomes. Two reviewers independently screened abstracts and full articles, and extracted data from eligible articles.

Results: Of 5531 citations, we removed 397 duplicates, screened 5134 abstracts, reviewed 240 full-text articles, and included 79 articles. Studies included 39 (49%) prospective cohorts, 23 (29%) retrospective cohorts, 14 (18%) randomized trials and 3 (4%) non-randomized trials. Examined regimens included tenofovir disoproxil fumarate/emtricitabine (n=70 studies, 87%), cabotegravir (n=3, 4%), tenofovir alafenamide/emtricitabine (n=3, 4%), tenofovir gel (n=2, 3%), maraviroc (n=2, 3%) and dapivirine (n=1, 1%). HIV acquisition with daily TDF/FTC was the most reported outcome (n=53, 67%). HIV incidence was low with event-driven TDF/FTC and did not differ from daily TDF/FTC (n=9, 90%). Long-acting injectable cabotegravir had superior prevention efficacy to TDF/FTC in two studies in gay and bisexual men, and cis-gender women. TAF/FTC was non-inferior to TDF/FTC in two articles on the DISCOVER trial. MVC-containing regimens were non-inferior to TDF-containing regimens in a phase 2 trial in cisgender women. Higher adherence was associated with optimal prevention. Older age (n=5), white race (n=2), recent PrEP start (n=5), and higher socioeconomic class were associated with PrEP adherence while younger age (n=4) and Black/African American race (n=3) were associated with lower adherence. The most examined adverse event was renal toxicity (n=20, 95%), with 15 studies (75%) reporting declines in creatinine clearance with TDF/FTC. DISCOVER found that TAF/FTC was superior to TDF/FTC in bone and renal safety.

Conclusion: Several PrEP regimens were effective in preventing HIV acquisition in diverse populations and will inform upcoming Canadian guidelines.


Lawrence Mbuagbaw
Associate Professor
McMaster University

Barriers and facilitators to improving the cascade of HIV care in Ontario: a mixed methods study

Abstract

Background:
Engagement in care is important for people living with HIV (PLH) to achieve optimal outcomes. Several strategies have been developed to improve client flow through the HIV care cascade, specifically targeting initiation of treatment, adherence to antiretroviral therapy (ART), retention in care, and engagement in care. We have previously identified effective care cascade strategies in a systematic review. The aim of this mixed methods study was to investigate barriers and facilitators to implementing effective interventions in HIV clinics in Ontario, Canada.

Methods:
We conducted a sequential explanatory mixed methods study. In the quantitative strand, we administered a survey to health workers who provide care to PLH to identify barriers and facilitators. In the qualitative strand, we conducted semi-structured interviews informed by the theoretical domains framework (TDF) with health workers and with PLH to explain our quantitative findings. Qualitative and quantitative data were merged to create meta-inferences.

Results:
Twenty health workers from 8 clinics in 9 cities in Ontario took the survey. Nine PLH and 10 health workers participated in the qualitative interviews. Clinics in Ontario implemented all the effective interventions identified from the literature for initiation of treatment, adherence to ART, and retention in care despite concerns about resources. Barriers to physical and financial access to care, the workload for tailored care, and expertise were identified by both health workers and PLH. Key facilitators were virtual care and client preparedness through education and peer support.

Conclusion:
Clinics in Ontario appear to implement several evidence-based strategies to improve PLH engagement. There is a need for more health workers with skills to address unique PLH needs. Virtual care is beneficial to both health workers and PLH.


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Patrick Gauthier Kamgang
Intern
Institut National De Santé Publique Du Québec (inspq)

Factors Associated With Reported Use of Needles/syringes already Used by Someone else among People Who Inject Drugs (PWID) in the SurvUDI network, February 2011 to March 2020

Abstract

Objective: To examine the correlates of reported use of needles/syringes already used by someone else (NSS) among PWID in the SurvUDI network.

Methods: From February 2011 to March 2020, participants (having injected in the past six months) were recruited mainly through harm reduction programs across the Province of Quebec and in Ottawa. Multiple participations were allowed (at least six months apart), with an interviewer-administered questionnaire completed each time. Questions about behaviours referred to the past 6 months unless stated otherwise. Regression analyses were performed using generalized estimating equations taking into account multiple participations, excluding missing values in univariate and multivariate models (8.6% questionnaires excluded). Variables, entered in the model based on a literature review, were retained if their p-value was <0.1 in univariate models. Significant variables (p-value <0.05) were retained in the multivariate model.

Results: Data from 4,077 participants (7,353 visits) were included. At their most recent visit, their mean age was 40.5 years (standard deviation=11.2 years) and the prevalence of NSS was 16.2%. Table 1 shows factors significantly associated with NSS.

Conclusion: Prevalence of NSS is relatively higher among PWID who were female at birth, are younger, live in semi-urban/rural sites, report “sex work”, inject frequently, use crack other than by injection or report difficulties accessing needles/syringes programs. These analyses are based on a convenience sample (prone to biases) and the observed associations might not be causal. However, they suggest a need for targeted interventions for these subgroups to increase the availability of sterile needles/syringes and for tailored counselling.


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