Background: Human immunodeficiency virus (HIV) remains a leading cause of morbidity worldwide, with over 50% of infections occurring in women. The vaginal microbiome has been shown to play a key role in mediating susceptibility. Specifically, a polymicrobial environment coupled with reduced Lactobacillus colonization is associated with bacterial vaginosis (BV), and increased risk of HIV infection. This study aimed to improve vaginal health among African/Caribbean/Black (ACB) women using intravaginal estrogen and/or probiotic interventions.

Methods: Forty-one ACB women completed a 30-day intervention, randomized to one of four treatment groups: RepHresh™ Pro-B™ probiotic delivered vaginally in combination with the intravaginal estradiol Estring®, oral probiotics with the Estring, vaginal probiotics alone, or the Estring alone. Feasibility was evaluated through enrolment, retention, and intervention protocol (IP) adherence rates, while safety was assessed according to adverse events (AEs) and comprehensive blood panels. In addition, genomic DNA was extracted from cervicovaginal lavage (CVL) samples for microbiome analysis.

Results: The enrolment and retention rates were 0.81 and 0.83 respectively, with an IP adherence greater than 0.70 for those that completed the study. Microbiome data revealed a positive treatment response in 41% (n=17) of participants, with no significant microbial shift occurring in an additional 41% (n=17) of participants. Intervention groups including the Estring and oral probiotic, along with the vaginal probiotic alone had the highest positive responses of 50% and 54% respectively. Amongst participants with a positive treatment response, an overall 13% increase in Lactobacillus spp. from baseline was observed one-week post-treatment. Furthermore, differential abundance analysis indicated a significant reduction in several polymicrobial species associated with BV including, Anaerobius and Prevotella.

Conclusion: Our results demonstrate acceptable enrolment, retention, and adherence, with no severe AEs reported. Preliminary findings also suggest the administration of intravaginal estrogen and probiotics are associated with beneficial shifts in the microbial microenvironment.

CTN 308; Clinicaltrials.gov NCT03837015

Background
Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are established methods of HIV prevention through the use of antiretroviral medications. However, the suitability of these tools for individuals with infrequent, higher-risk HIV exposures might be limited due to cost, high pill burden and/or barriers to care. PEP-in-pocket (PIP) involves prospectively identifying such individuals, proactively prescribing them 28 days of PEP medication, and providing instructions on when to initiate medications and how to follow up with care. We present long-term follow-up of a cohort of patients using PIP for HIV prevention.

Methods
We conducted a retrospective evaluation of the clinical characteristics and outcomes of patients using PIP for HIV prevention. Patients referred for PrEP or PEP care were offered PIP if they reported a low frequency (0-4 per year) of high-risk HIV exposures of any type. HIV prevention method was chosen through shared decision-making between patients and clinicians and was outside the realm of this study. Patients were followed at regular 4-6 months intervals.

Results
We followed 112 patients aged 20-69 for a total of 183.8 patient-years. 108 (96%) patients were assigned male at birth. Thirty-five (31%) patients self-initiated a total of 64 courses of PIP during the observation period. Patients transitioned between HIV prevention modalities as circumstances warranted: 34 (31%) changed from PIP to PrEP, and 33 (30%) changed from PrEP to PIP. There were 18 episodes of bacterial sexually transmitted infections in 13 individuals (12%). No HIV seroconversions were detected.

Conclusions
PIP is an innovative HIV prevention strategy for individuals with a low frequency of higher-risk exposures, and provides patients with autonomy and agency over their care. Patients may transition between PIP and PrEP based on evolving risk. PIP should be included with PEP and PrEP as a biomedical HIV prevention option for individuals at risk for infection.

Background: Pre-exposure prophylaxis (PrEP) using oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) has been a standard of care HIV prevention intervention since Health Canada approval in 2016, but many scientific advances have occurred since Canadian guidelines were published in 2017.
Methods: We conducted a systematic review of PrEP clinical trials and cohort studies published from July 2017-July 2022. We searched Medline and Embase 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 publications; data from eligible articles were extracted onto a standardized form. Here we summarize study designs, PrEP regimens, and populations included in the first 45 eligible manuscripts.
Results: Of 5531 abstracts identified, we removed 395 duplicates, screened 5136 abstracts, reviewed 241 full-text articles, and deemed 104 eligible for inclusion. The first 45 eligible studies reported on 75841 participants, and included 25 (56%) prospective cohorts, 16 (36%) randomized trials, 2 (4%) non-randomized trials and 2 (4%) retrospective cohorts. The primary or novel regimen examined was most commonly TDF/FTC (n=45, 67%), followed by tenofovir alafenamide/emtricitabine (n=7, 16%), long-acting injectable cabotegravir (n=3, 7%), tenofovir gel (n=2, 4%), maraviroc (n=2, 4%) and dapivirine (n=1, 2%). Studies covered most key populations including gay, bisexual and other men who have sex with men (n=24, 53%), transgender women (n=15, 33%), heterosexual women (n=18, 40%), heterosexual men (n=7, 16%) and transgender men (n=4, 9%), though none so far have addressed people who inject drugs. Most were conducted in Africa (n=15, 33%), followed by North America (n=10, 22%), Europe (n=3, 7%), Asia (n=3, 7%) and Australia (n=3, 7%); multiple continents were included for n=10 (22%) studies.
Conclusions: Preliminary findings suggest an expansive literature on multiple PrEP regimens in most key populations to inform forthcoming Canadian guidelines.

HIV guidelines offer switch strategies for virologically suppressed people with HIV-1 (PWH), but long-term clinical follow-up after the regimen switch is often lacking. We present 96-week (W) outcomes on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in an open-label extension (OLE) that followed 144W of blinded DTG-based treatment in two treatment-naïve studies.

2 randomized, double-blind, phase 3 studies of B/F/TAF were conducted in PWH initiating first-line therapy – Study 1489: B/F/TAF vs dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) and Study 1490: B/F/TAF vs DTG+F/TAF. We examined cumulative results for participants who were originally randomized/treated with either DTG/ABC/3TC or DTG+F/TAF for 144W and then switched to 96W of B/F/TAF in an OLE (total of 240W of follow-up). Efficacy analysis included HIV-1 RNA <50 copies/mL at each visit after starting B/F/TAF (missing=excluded [M=E] analysis); safety by adverse events (AEs) and laboratory results.

In 1489, 254/315 (81%) participants randomized to DTG/ABC/3TC entered the OLE. In 1490, 265/325 randomized to DTG+F/TAF entered the OLE. After switch to B/F/TAF, efficacy was >96% at every visit through W240 (M=E). Eleven participants had HIV-1 RNA ≥ 50 copies/mL at time of switch, two of whom were later found to have M184V while on blinded DTG/ABC/3TC and resuppressed on B/F/TAF. No resistance detected to any components of B/F/TAF. Across both studies (1489: n=254, 1490: n=265), 2/519 (0.4%) switch participants experienced an AE leading to drug discontinuation during the OLE, none were renal. Grade 3 drug-related AE occurred in one participant, no Grade 4 AEs. Participants switching from DTG/ABC/3TC had numerically greater weight increases 2.4 kg (-0.4, 5.6) than those switching from DTG+F/TAF 1.3 (-1.9, 5.0).

Over 5 years of follow-up, adults initially taking DTG/ABC/3TC or DTG+F/TAF who then switched to B/F /TAF maintained high virologic suppression and few discontinuations. These results confirm long-term safety and efficacy of B/F/TAF in those who switch from a DTG-containing regimen.

Lenacapavir (LEN), a potent first-in-class inhibitor of HIV-1 capsid function, is approved in Canada as a long-acting agent for treatment and in development for prevention of HIV-1.

CAPELLA is an ongoing, phase 2/3 study in heavily treatment-experienced (HTE) people with HIV-1 (PWH) with multidrug-resistance. 36 participants randomized (2:1) to add oral LEN or placebo to their failing regimen. At D15, oral LEN arm received subcutaneous (SC) LEN (Q6M); placebo arm started the oral LEN lead-in, followed by SC Q6M. All randomized participants initiated an investigator selected, optimized background regimen (OBR) at D15. An additional 36 participants started OBR concurrent with LEN (oral lead-in SC) in a non-randomized cohort. We report the Week (W) 52 efficacy and safety results from both cohorts

Of 72 participants enrolled, 64% had CD4 < 200 cells/μL, 46% had HIV-1 resistant to all 4 major classes (NRTI, NNRTI, PI, INSTI), and 53% had OBR with 1 or no fully active agents. 78% (56/72) achieved VL< 50 c/mL and 82% (59/72) achieved VL< 200 c/mL. CD4 count increased by a median 84 cells/μL (Q1 to Q3: 21 to 153) and the proportion of participants with CD4 count ≥200 cells/ul increased from 36% at baseline to 68%. Ten participants had emergent LEN resistance (8 previously reported); 4 of 10 subsequently suppressed. One participant discontinued due to injection site nodule (Grade 1). The most common injection site reaction (ISR) was swelling (28% [20/72] and 17% [12/70] after the 1 and 2 SC doses, respectively) and were mild or moderate. The most common AEs (excluding ISRs) were nausea and diarrhea (14% each).

In HTE PWH, LEN was well tolerated and in combination with OBR led to high and sustained rate of virologic suppression at W52. These results support the potential role for LEN for treatment of multidrug resistant HIV-1 infection.

Objectives: The Choosing Wisely Guideline from the Association of Medical Microbiology and Infectious Disease Canada suggests not repeating CD4 measurements in patients with HIV infection if the CD4 count is above 500 /µL with suppressed HIV viral loads for 2 years. A chart audit in the HIV clinic at our centre found that 67% of CD4 orders were deemed to be unnecessary based on current guidelines. Our objective was to reduce CD4 count testing per patient visit in the HIV clinic by 25%.

Methods: A fishbone framework for root cause analysis revealed several potential causes underlying frequent ordering of CD4 counts. A series of Plan-Do-Study-Act (PDSA) cycles were undertaken, starting with education sessions for health care providers, followed by creation of a computerized clinical decision support (CCDS) pop up that would trigger when a CD4 count was ordered less than a year since the last one. Frequency of CD4 count testing per patient visit to our clinic was the primary outcome measure. The number of times the pop up triggered per month was the process measure. The number of patients who required a CD4 count with their routine blood work but did not get one was a balancing measure.

Results: After implementation, there was a 52% reduction in CD4 count testing per patient visit, with no adverse outcomes for patients. The CCDS was more effective than education, consistent with previous studies. The intervention represents >$23,000 annualized savings.

Conclusion: We present a novel and straightforward intervention that can implemented in HIV clinics and results in substantial cost savings in addition to aligning patient care with best practices.