Challenges recruiting and retaining people at risk for HIV who use methamphetamine in a randomized PrEP adherence trial in Seattle, WA.

BACKGROUND: Methamphetamine is associated with increased HIV risk and suboptimal adherence to pre-exposure prophylaxis (PrEP). Interventions to support PrEP adherence for people who use methamphetamine are needed. METHODS: We evaluated peer navigation to support adherence among people initiating PrEP who use methamphetamine. The HIV Prevention in Methamphetamine Users (HMU!) study enrolled participants from May 2018-January 2022 in Seattle, WA, and followed them for 6 months. Surveys collected sociodemographic, drug use, and sexual behavior data at enrollment, month 3, and month 6. Dried blood spots (DBS) were collected at months 1, 3, and 6 to measure PrEP adherence. RESULTS: We enrolled 21 participants of a target sample of 40, of whom 20 were prescribed PrEP. Nine participants (43%) received peer navigation and 12 (57%) received standard of care or text messaging. At baseline, most participants reported at least weekly methamphetamine use (17, 81%) and condomless receptive anal intercourse (CRAI) (16, 76%). One-third reported CRAI with a partner with HIV. Among those who provided a DBS, 78% and 50% had results commensurate with ≥4 pills/week at the month 3 and 6 visit, respectively. More than half of those prescribed PrEP completed a month 6 visit (11, 55%). Retention was not associated with peer support compared to standard of care or text messaging (p = .20). CONCLUSIONS: We enrolled half our target sample size despite extensive recruitment efforts. As expected, participants had challenges with PrEP adherence and persistence. While peer navigation interventions should be studied further, additional interventions are likely needed to support PrEP uptake, adherence, and persistence among people who use methamphetamine.

Barriers and facilitators to implementing a Pharmacist, Physician, and Patient Navigator-Collaborative Care Model (PPP-CCM) to treat hepatitis C among people who inject drugs.

BACKGROUND: Direct-acting antivirals (DAAs) offer an unprecedented opportunity to eliminate hepatitis C virus (HCV) infection, yet barriers among people who inject drugs (PWID) remain. Having pharmacists provide care through collaborative drug therapy agreements (CDTAs) offers a promising solution. We developed and piloted a Pharmacist, Physician, and Patient Navigator-Collaborative Care Model (PPP-CCM) which utilized pharmacists to directly deliver HCV care at community organizations serving PWID. We conducted formative evaluation of the PPP-CCM pilot to characterize implementation experiences. METHODS: The PPP-CCM was implemented from November of 2020 through July of 2022. Formative evaluation team members observed implementation-related meetings and conducted multiple site visits, taking detailed fieldnotes. Fieldnotes were iteratively reviewed to identify barriers and facilitators to implementation and used to inform 7 key informant interviews conducted with programmatic staff at the end of the pilot. All data were analyzed using a Rapid Assessment Process (RAP) guided by the Consolidated Framework for Implementation Research (CFIR). The formative evaluation team shared results with program stakeholders (pharmacists, physicians, and other site staff) to verify and expand on learnings. RESULTS: Evaluation of PPP-CCM revealed 5 themes, encompassing all CFIR domains: 1) PPP-CCM was feasible but challenging to deliver efficiently; 2) the pharmacist role and characteristics (e.g., being flexible, available, and patient-centered) were key to PPP-CCM successes; 3) the PPP-CCM team met challenges engaging patients over time, but some team-based strategies helped; 4) community site characteristics (e.g., existing trusting relationships with PWID and physical space that enabled program visibility) were important contributors; and 5) financial barriers may limit PPP-CCM scale-up and sustainability. CONCLUSION: PPP-CCM is a novel and promising approach to HCV care delivery for PWID who may previously lack engagement in traditional care models, but careful attention needs to be paid to financial barriers to ensure scalability and sustainability.

Qualitative inquiry into perceptions of HIV pre-exposure prophylaxis among people who inject drugs living with hepatitis C in Seattle, WA, USA.

BACKGROUND: The incidence of HIV among persons who inject drugs (PWID) in the USA has been increasing since 2014, signaling the need to identify effective ways to engage PWID in HIV prevention services, namely pre-exposure prophylaxis (PrEP). Yet, the uptake of PrEP in this population is minimal compared to other populations at risk of HIV acquisition. In this work, we sought to explore knowledge, attitudes, and perspectives of PrEP acceptability among PWID. METHODS: In the context of a pilot study to explore the acceptability of pharmacy-based hepatitis C virus (HCV) treatment, we conducted semi-structured interviews (n = 24) and focus groups (n = 4, 16 participants) with people who were living with HCV and reported active injection drug use (≤ 90 days since last use). Participants were asked open-ended questions about their familiarity with and motivation to use PrEP. As part of a sub-analysis focused on PrEP, qualitative data were analyzed using a Rapid Assessment Process, where three coders used structured templates to summarize qualitative data and iteratively reviewed coded templates to identify themes. Participants also completed short quantitative questionnaires regarding drug use history and attitudes toward health concerns. RESULTS: Forty-seven percent of participants expressed having little or no concern regarding HIV acquisition. Targeted analyses focused on HIV prevention identified three themes, which help characterize behavioral determinants of nonadoption. First, knowledge of PrEP was limited among PWID and influenced by infrequent open community discussions around HIV risk. Second, PWID perceived sexual behaviors-but not injection drug use-as a motivator for HIV risk prevention. Finally, PWID identified many individual and environmental barriers that hinder PrEP uptake. CONCLUSION: Among PWID, PrEP is rarely discussed and concerns about the feasibility of using daily PrEP are common. Taken with the prevalent perception that drug use is not a high risk for HIV acquisition, our findings point to opportunities for public health work to target PrEP education to PWID and to leverage other successful interventions for PWID as an opportunity to provide PrEP to this vulnerable population.

Health care-seeking experiences for people who inject drugs with hepatitis C: Qualitative explorations of stigma.

INTRODUCTION: People who inject drugs (PWID) have complex health needs and often experience poor health outcomes. For PWID, intersectional experiences of stigma and other social vulnerabilities may influence their experiences navigating medical care. We conducted a targeted subanalysis of qualitative interview data collected to inform development of a community-pharmacist care model for hepatitis C (HCV) among PWID to explore intersectional influences on health care-seeking experiences. METHODS: The study recruited participants from community organizations in Seattle, Washington, and participants were eligible if they reported injection drug use within 3 months and having HCV. Study staff conducted semi-structured interviews and two independent coders transcribed and initially analyzed them using a Rapid Assessment Process, guided by the Consolidated Framework for Implementation Research. Themes emerged regarding intersections of stigma and social vulnerabilities; thus, we conducted a targeted subanalysis guided by Fundamental Cause Theory and Earnshaw et al.'s Stigma Framework. RESULTS: Forty participants (65% male; 47% non-white) reported multiple social vulnerabilities (e.g., regarding unstable housing and food insecurity). Qualitative analysis identified that receiving health care in the context of social vulnerability is challenging and burdensome (Theme 1); health care interactions are fraught with stigma stemming from intersectional vulnerabilities (Theme 2); and the belief that abstaining from drug use is needed to prove worthiness for care (Theme 3). PWID described experiencing multiple social vulnerabilities (e.g., unmet basic needs) that made seeking health care burdensome. Interactions with health care teams further reinforced participants' feelings of shame about their drug use, which influenced how participants expressed their care preferences and felt heard by providers. And as PWID navigated health care, they felt that their status as an active drug user was used to control and sometimes coerce their access to services, discouraging PWID from seeking needed care. CONCLUSIONS: Stigma and social vulnerabilities play a pervasive and intersecting role in the health care-seeking experiences of PWID and negatively impact their ability to navigate and receive care they need. Evidence-based stigma reduction interventions at multiple levels, coupled with person-centered approaches to care delivery, may help to mitigate negative impacts.

'Treat my whole person, not just my condition': qualitative explorations of hepatitis C care delivery preferences among people who inject drugs.

BACKGROUND: The advent of direct-acting antivirals (DAAs)-a form of hepatitis C (HCV) treatment associated with shorter treatment course and greater efficacy-offers an unprecedented opportunity to eliminate HCV, but only if care delivery systems are developed to extend treatment to people who inject drugs (PWID). To support the design of a community-pharmacy program, we explored perspectives of PWID with chronic HCV with regard to barriers, motivators, preferences, and prior experiences related to HCV treatment and pharmacists. METHODS: We conducted semi-structured interviews with people living with HCV who reported active injection drug use. Participants were recruited from local community service and clinical organizations in the Seattle, Washington region, and focus groups and interviews were conducted in-person or via phone/video-conference. Rapid Assessment Process was used to analyze qualitative data. Dual coders used structured templates to summarize findings and engaged in iterative review to identify themes. RESULTS: Among the 40 participants, 65% were male, 52.5% were white, and 80% were not stably housed. On average, participants had been injecting drugs for 14 years and living with HCV for 6 years. Analyses revealed 3 themes: (1) limited knowledge regarding HCV and DAA treatments; (2) barriers/motivators for receiving treatment included fear of side effects, prior stigmatizing behaviors from physicians, and desire to protect relatives and the PWID community from HCV transmission; and (3) preferences for HCV care delivery, including a need for person-centered, low-barrier, and collaborative treatment integrated with other care (e.g. primary care and addiction treatment) for PWID. Participants were generally receptive to a community-pharmacy model for HCV treatment, but prior interactions with pharmacists were mixed and there were some concerns expressed that care delivered by pharmacists would not be equivalent to that of physicians. CONCLUSIONS: Even in the direct-acting antivirals era, people who inject drugs still face major barriers to hepatitis C treatment which may be reduced by providing low-barrier points of access for care through pharmacists. Key recommendations for community-pharmacy design included providing care team training to reduce stigma and ensuring care team structures and culture target PWID-specific needs for education and engagement.

Patient-Focused Selection of PrEP Medication for Individuals at Risk of HIV: A Narrative Review.

Pre-exposure prophylaxis (PrEP) medication is a key component of the HIV prevention strategy in the US, which has been demonstrated to be highly effective in preventing HIV acquisition among individuals at risk. Two PrEP medications are currently approved: emtricitabine/tenofovir disoproxil fumarate (Truvada®; F/TDF) was approved by the US Food and Drug Administration in 2012, followed by emtricitabine/tenofovir alafenamide (Descovy®; F/TAF) in 2019. An ongoing randomized, double-blind, Phase 3 study (DISCOVER) demonstrated that F/TAF had non-inferior efficacy to F/TDF. While both medications have been found to be efficacious and well tolerated, several studies have identified that important differences exist with regards to pharmacokinetics, bone and renal safety profiles, and other factors. In this narrative review, we conducted a comprehensive evaluation of the populations at risk of HIV who may also be affected by, or at risk of, bone or renal conditions. We reviewed the safety profiles of F/TDF and F/TAF to develop an evidence-based algorithm for selecting the appropriate PrEP medication, based on biological, behavioral, and health characteristics of an individual at risk of HIV, and considered how the choice of PrEP medication may or may not compound safety concerns for these individuals. We identified that the introduction of F/TAF provides a valuable alternative to F/TDF, allowing the personalization of PrEP. F/TAF may be the preferred medication for cisgender men and transgender women at risk of HIV infection who are predisposed to, or already have, bone or renal conditions. While the approval of F/TAF is the first step in personalization of PrEP, additional options are still warranted to help accommodate the wide spectrum of individuals at risk of HIV with different lifestyles, medical histories, preferences, and requirements.

Pre-exposure prophylaxis (or PrEP) prevents HIV acquisition in individuals at risk of HIV infection. There are currently two approved options for PrEP in the US; both are oral medications. The first option, approved in 2012, is a combination of two drugs called emtricitabine/tenofovir disoproxil fumarate­also known as Truvada^® or F/TDF. The second option, approved in 2019, is a combination of emtricitabine and a different prodrug, tenofovir alafenamide­this combination is called Descovy^® or F/TAF. Both options are 99% effective in preventing HIV if taken daily. While the risk of serious side effects from taking either of the PrEP medications is low, F/TAF has demonstrated less effect on bone and kidney health, and may be the preferred option in people with bone or kidney conditions, or in those at risk of developing osteoporosis or having risk factors for kidney disease, such as people living with diabetes or high blood pressure. As the risk of HIV sometimes overlaps with risks to bone and renal health according to race/ethnicity, poverty, alcohol/substance use, smoking tobacco, and taking other medications, F/TAF as an alternative PrEP medication allows the PrEP choice to depend on the broader health conditions of the individual. 'Personalized medicine' means that medicines can be chosen to suit an individual's biology, behavior, lifestyle, and overall health. The approval of F/TAF is the first step in personalization of PrEP medication, while additional options need to be researched to meet the requirements of all individuals at risk of HIV.

The Role of Pharmacies in the HIV Prevention and Care Continuums: A Systematic Review.

The role of pharmacists in the treatment of HIV has expanded beyond medication dispensing to include a host of cost-effective, evidence-based strategies across the HIV prevention and care continuums. However, wide-scale adoption of pharmacy-based HIV prevention and treatment interventions has been slow. We conducted a systematic review to evaluate the evidence on the role of pharmacists across the HIV prevention and care continuums. Thirty-two studies were identified, most of which provided evidence of feasibility of HIV testing and efficacy of non-prescription syringe sale services in pharmacies. However, only two studies implemented an experimental design to rigorously test pharmacy-based strategies. Notably, no pharmacy-based strategies have specifically targeted the highest HIV risk populations such as black and Latinx men who have sex with men, women, or trans populations. Efficacy trials and effectiveness studies should rigorously test existing pharmacy-based strategies to build greater support for wide-scale adoption and implementation. Moreover, in order to integrate pharmacies into the strategy to end the HIV epidemic, studies are needed to ensure that pharmacy-based HIV prevention and treatment services can reach the highest risk populations.

Implementation of a community pharmacy-based pre-exposure prophylaxis service: a novel model for pre-exposure prophylaxis care.

Background National guidelines for the provision of HIV pre-exposure prophylaxis (PrEP) to reduce a person's risk of acquiring HIV were made available in 2014. We created a pharmacist-managed HIV PrEP clinic in a community pharmacy setting at Kelley-Ross Pharmacy in Seattle, WA, USA. METHODS: The clinic operates under a collaborative drug therapy agreement based on these guidelines. This allows pharmacists to initiate and manage tenofovir disoproxil fumarate/emtricitabine under the supervision of a physician medical director. RESULTS: Between March 2015 and February 2018, 714 patients were evaluated and 695 (97.3%) initiated PrEP. Five hundred and thirteen (74%) patients began medication the same day as their initial appointment. Of the prescriptions filled in our pharmacy, 90% of patients had a mean proportion of days covered (PDC) greater than 80%, and 98% had a zero-dollar patient responsibility per month, including uninsured individuals. 19% of patients were lost to follow up, with an effective drop-out rate of 25%. Two hundred and seven diagnoses of sexually transmissible infections were made. There were no HIV seroconversions in the service. CONCLUSION: The pharmacist-managed PrEP clinic proved to be a successful alternative model of PrEP care, with high initiation rates and low drop-out and lost-to-follow-up rates. This may benefit individuals who do not access PrEP in traditional health care settings or where PrEP access is scarce. Financial sustainability of the model was dependent on the ability of pharmacists in the clinic to bill insurance plans for their services in accordance with Washington State legislative changes requiring commercial insurances to recognise pharmacists as providers.

Role of carbonic anhydrase II in ectopic calcification.

INTRODUCTION: Osteopontin (OPN) is a potent inhibitor of ectopic calcification. Previous studies suggested that, in addition to blocking apatite crystal growth, OPN promoted regression of ectopic calcification by inducing the expression of acid-generating carbonic anhydrase II (CAR2) in monocyte-derived cells. METHODS: To test this hypothesis, OPN and CAR2 expression and calcification of subcutaneously implanted glutaraldehyde-fixed bovine pericardium (GFBP) were studied in CAR2 mutant mice. RESULTS: Consistent with previous studies in Black Swiss mice, GFBP calcified to a greater extent in OPN-deficient mice compared to wild types on the C57Bl/6 background. GFBP implanted in CAR2-deficient mice (CAR2(-/-)) were significantly more calcified than those implanted into wild-type mice (CAR2(+/+)) [37+/-5 vs. 20+/-6.5 microg Ca/mg tissue, respectively, at 30 days (P<.001), and 42+/-5 versus 20+/-4 microg Ca/mg tissue at 60 days, respectively (P<.001)]. On the other hand, OPN levels within and surrounding the implants were similar in CAR2(+/+) and CAR2(-/-) mice, suggesting that OPN expression in the absence of CAR2 was not sufficient to mitigate ectopic calcification. CONCLUSIONS: These results indicate that CAR2 expression is an important regulator of ectopic calcification, potentially by facilitating OPN mediated mineral regression.

Mitigation of ectopic calcification in osteopontin-deficient mice by exogenous osteopontin.

Ectopic calcification is a major cause of bioprosthetic heart valve failure. New therapeutic opportunities are offered by the growing understanding that ectopic calcification is an actively regulated process involving several key gene products. One of these products, osteopontin (OPN), is a glycosylated phosphoprotein previously shown to inhibit apatite crystal formation, induce carbonic anhydrase II, and promote mineral resorption. In this study, OPN-deficient mice (OPN-/-) were utilized as an in vivo model to stimulate the ectopic calcification of glutaraldehyde-fixed bovine pericardium (GFBP) tissue and to examine OPN delivery and structure-function relationships with respect to its anti-calcific activity. Significant calcification of GFBP tissue was obtained within 7 days of subcutaneous implantation in OPN-/- mice. Direct rescue of the calcification phenotype was achieved by the administration of exogenous recombinant rat, histidine-fused OPN (rat His-OPN) to the implant site via soluble injection (up to 72% mitigation achieved) or adsorption onto the implant materials (up to 91% mitigation achieved). Effects were specific, since neither fibronectin nor polyhistidine alone could mitigate calcification of GFBP. The maximum anti-calcific effect was achieved only when rat His-OPN was adequately phosphorylated and contained a functional arginine-glycine-aspartate (RGD) cell adhesive domain. Furthermore, CAII levels in host cells surrounding GFBP were greatest when phosphorylated, RGD-containing rat His-OPN was adsorbed. These data suggest that both physical inhibition, mediated by phosphorylation sites in OPN, as well as the induction of CAII and mineral regression, mediated by the RGD domain, contribute to the unique ability of OPN to mitigate ectopic calcification of bioprosthetic valve tissue.

Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo.

Osteopontin (OPN) is abundantly expressed in human calcified arteries. To examine the role of OPN in vascular calcification, OPN mutant mice were crossed with matrix Gla protein (MGP) mutant mice. Mice deficient in MGP alone (MGP(-/-) OPN(+/+)) showed calcification of their arteries as early as 2 weeks (wk) after birth (0.33 +/- 0.01 mmol/g dry weight), and the expression of OPN in the calcified arteries was greatly up-regulated compared with MGP wild-types. OPN accumulated adjacent to the mineral and colocalized to surrounding cells in the calcified media. Cells synthesizing OPN lacked smooth muscle (SM) lineage markers, SM alpha-actin and SM22alpha. However, most of them were not macrophages. Importantly, mice deficient in both MGP and OPN had twice as much arterial calcification as MGP(-/-) OPN(+/+) at 2 wk, and over 3 times as much at 4 wk, suggesting an inhibitory effect of OPN in vascular calcification. Moreover, these mice died significantly earlier (4.4 +/- 0.2 wk) than MGP(-/-) OPN(+/+) counterparts (6.6 +/- 1.0 wk). The cause of death in these animals was found to be vascular rupture followed by hemorrhage, most likely due to enhanced calcification. These studies are the first to demonstrate a role for OPN as an inducible inhibitor of ectopic calcification in vivo.