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Background: Antiretroviral therapy (ART) through universal test and treat (UTT) and HIV pre-exposure prophylaxis (PrEP) substantially reduces HIV-related mortality and incidence. Effective ART based prevention has not translated into population-level impact in southern Africa due to sub-optimal coverage among youth. We aim to investigate the effectiveness, implementation and cost effectiveness of peer-led social mobilisation into decentralised integrated HIV and sexual reproductive health (SRH) services amongst adolescents and young adults in KwaZulu-Natal (KZN)., Methods: We are conducting a type 1a hybrid effectiveness/implementation study, with a cluster randomized stepped-wedge trial (SWT) to assess effectiveness and a realist process evaluation to assess implementation outcomes. The SWT will be conducted in 40 clusters in rural KZN over 45 months. Clusters will be randomly allocated to receive the intervention in period 1 (early) or period 2 (delayed). 1) Intervention arm: Resident peer navigators in each cluster will approach young men and women aged 15-30 years living in their cluster to conduct health, social and educational needs assessment and tailor psychosocial support and health promotion, peer mentorship, and facilitate referrals into nurse led mobile clinics that visit each cluster regularly to deliver integrated SRH and differentiated HIV prevention (HIV testing, UTT for those positive, and PrEP for those eligible and negative). Standard of Care is UTT and PrEP delivered to 15-30 year olds from control clusters through primary health clinics. There are 3 co-primary outcomes measured amongst cross sectional surveys of 15-30 year olds: 1) effectiveness of the intervention in reducing the prevalence of sexually transmissible HIV; 2) uptake of universal risk informed HIV prevention intervention; 3) cost of transmissible HIV infection averted. We will use a realist process evaluation to interrogate the extent to which the intervention components support demand, uptake, and retention in risk-differentiated biomedical HIV prevention., Discussion: The findings of this trial will be used by policy makers to optimize delivery of universal differentiated HIV prevention, including HIV pre-exposure prophylaxis through peer-led mobilisation into community-based integrated adolescent and youth friendly HIV and sexual and reproductive health care., Trial Registration: ClinicalTrials.gov Identifier-NCT05405582. Registered: 6th June 2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Long-acting formulations of the potent antiretroviral prodrug tenofovir alafenamide (TAF) hold potential as biomedical HIV prevention modalities. Here, we present a rigorous comparison of three animal models, C57BL/6 J mice, beagle dogs, and merino sheep for evaluating TAF implant pharmacokinetics (PKs)., Methods: Implants delivering TAF over a wide range of controlled release rates were tested in vitro and in mice and dogs. Our existing PK model, supported by an intravenous (IV) dosing dog study, was adapted to analyze mechanistic aspects underlying implant TAF delivery., Results: TAF in vitro release in the 0.13 to 9.8 mg d -1 range with zero order kinetics were attained. Implants with equivalent fabrication parameters released TAF in mice and sheep at rates that were not statistically different, but were 3 times higher in dogs. When two implants were placed in the same subcutaneous pocket, a two-week creep to C max was observed in dogs for systemic drug and metabolite concentrations, but not in mice. Co-modeling IV and TAF implant PK data in dogs led to an apparent TAF bioavailability of 9.6 in the single implant groups (compared to the IV group), but only 1.5 when two implants were placed in the same subcutaneous pocket., Conclusions: Based on the current results, we recommend using mice and sheep, with macaques as a complementary species, for preclinical TAF implant evaluation with the caveat that our observations may be specific to the implant technology used here. Our report provides fundamental, translatable insights into multispecies TAF delivery via long-acting implants., (© 2022. The Author(s).)

Background: Long-acting injectable cabotegravir (CAB-LA) represents a new additional option for HIV prevention in people at substantial risk of HIV infection that may fill the gaps in pre-exposure prophylaxis (PrEP) uptake, adherence, and retention in users having difficulty with oral PrEP. Data from clinical trials demonstrated that CAB-LA was safe, highly effective, and well-accepted for HIV prevention. However, the occurrence of breakthrough HIV infections despite timely injections, HIV seroconversion timing and patterns, risk of selection and dissemination of resistance-associated mutations to integrase inhibitors, complexity of follow-up, logistical considerations, and its cost effectiveness compared with oral PrEP constitute significant issues for the integration of CAB-LA into clinical routine., Findings: These concerns need to be addressed before moving forward with large-scale implementation programmes. Pilot and implementation projects are required in the following areas: HIV testing algorithms, patient education, clinic procedures, protocols for switching and discontinuation, efficacy and safety in populations not included in clinical trials, and demedicalization processes. The development of models to increase the uptake of, adherence to, and persistence with and after CAB-LA injections will also be of paramount importance for success. Lessons learned from these projects will increase experience, staff expertise, and organizational and training capacities to support the roll-out of this new agent as part of HIV prevention programmes., Conclusion: CAB-LA has not yet achieved its full potential in HIV prevention, and strong commitment from all stakeholders is required to push CAB-LA as a game-changer in HIV response., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Despite efficacy in HIV prevention, Pre-exposure Prophylaxis (PrEP) is underutilized in the US, especially among populations at highest risk. PrEP-related stigma may play a role. We developed measures of PrEP-related stigma dimensions and PrEP adherence. We administered them to current PrEP users. We hypothesized that PrEP-related stigma would negatively impact PrEP adherence. Questionnaire measures were developed using data from previous qualitative work and existing validated HIV-related stigma measures. The resultant survey was administered to current PrEP users from two Birmingham, Alabama PrEP clinics. Plasma tenofovir disoproxil fumarate levels were collected to measure PrEP adherence. Exploratory factor analyses were performed to determine the factor structure of each PrEP-related stigma dimension (internalized, perceived, experienced, anticipated, disclosure concerns). Separate binary logistic (or linear) regressions were performed to assess associations between PrEP-related stigma dimensions and adherence (treatment adherence self-efficacy, self-reported adherence, and plasma tenofovir levels), adjusting for education, race, and time on PrEP. In 2018, 100 participants completed the survey, with 91 identifying as male and 66 as white. Only internalized stigma was associated with lower self-reported PrEP adherence. Exploratory mediation analyses suggested that the association between all stigma dimensions and self-reported PrEP adherence is mediated by PrEP adherence self-efficacy. No associations were found between any PrEP-related stigma measures and plasma tenofovir levels. Internalized PrEP stigma may reduce PrEP adherence, possibly by reducing PrEP adherence self-efficacy among experienced PrEP users. Further investigation of how stigma dimensions affect PrEP adherence in populations at risk for HIV may shed light on drivers of PrEP underutilization., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

User costs constitute a barrier to the uptake of HIV pre-exposure prophylaxis (PrEP), but their magnitude appears rarely assessed. In this prospective observational study, we assessed self-reported out-of-pocket expenses (OOPE) and time spent on clinic visits during a PrEP demonstration project in Eswatini. At six public primary care clinics, 240 PrEP users and other clinic attendees were interviewed after a clinic visit. Among the 79.2% of clinic attendees reporting any medical OOPE (e.g., expenses for consultations or drugs) and/or non-medical OOPE (e.g., expenses for transport, food, or phone use), the median total OOPE was $1.36 (IQR 0.91-1.96). Non-medical OOPE occurred mostly due to transport expenses. The median travel time for a clinic visit was 1.0 h (IQR 0.67-2.0). The median time spent in the clinic was 2.0 h (IQR 1.15-3.0). The median opportunity cost of a clinic visit was $7.54 (IQR 5.42-11) when valuing time spent on a clinic visit with Eswatini's per-capita gross domestic product. Our findings can guide measures to reduce the user costs of PrEP in Eswatini and other contexts in which oral PrEP is provided through health care facilities., (© 2022. The Author(s).)

Although roll-out of HIV pre-exposure prophylaxis (PrEP) has been reported to have changed contexts of HIV risk in areas where it was well-implemented. The rate of its uptake and retention amongst young females has not been described in Gauteng Province. This paper aimed at assessing PrEP uptake and retention among young females in Gauteng Province. Total of young females who tested HIV across five clinics from 01/January/2017 to 31/December/2020 was 19,671 with 17,937 tested HIV negative. Of the HIV tested negative, PrEP was initiated to 1307 (7%). The analysis revealed that 27% of young females returned for their first follow up visit after PrEP initiation, while third month declined to 14%, fourth month to 11%, and fifth month to 3%, sixth month to 2% and seventh month at 1% and from the eighth month, the rate of follow up was 0%. Uptake and retention of PrEP was low among young females as measured against the total tested HIV negative., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: HIV rates are increasing in rural areas, and adolescents are disproportionately affected. HIV pre-exposure prophylaxis (PrEP) is a daily pill that is effective at preventing HIV; however, PrEP uptake among adolescents is low. PrEP is dependent on primary care providers (PCPs) prescribing it, but research has overwhelmingly sampled urban PCPs. This study compared the PrEP awareness, practices, and comfort between rural and urban family medicine physicians., Methods: A total of 256 family medicine physicians in the United States were recruited from a Qualtrics panel to complete an online cross-sectional survey between July 15 and August 9, 2022. Participants completed items assessing their demographic characteristics and PrEP awareness, practices, and comfort. A chi-square test of independence and multiple logistic regression were used to determine rural/urban differences., Findings: Rural family medicine physicians were less comfortable than urban family medicine physicians in providing sexual risk reduction counseling to adolescents, telling an adolescent patient their HIV test result was HIV positive, and implementing all of the PrEP clinical activities for adolescents., Conclusions: Education, skill-building, and collaborative partnership interventions could improve the comfort levels of rural family medicine physicians in implementing the PrEP guidelines for their adolescent patients. Future research is needed to understand the factors that explain the differences in PrEP-related attitudes and practices between urban and rural family medicine physicians. Results from such studies could inform provider-based interventions that ultimately increase PrEP use and decrease HIV rates among rural adolescents., (© 2022 National Rural Health Association.)

Introduction: Fewer than a quarter of people considered to have factors associated with HIV acquisition are prescribed pre-exposure prophylaxis (PrEP) in the United States. Prior studies demonstrate disparities in provider comfort and knowledge regarding PrEP, suggesting a need for provider capacity building to support widespread PrEP availability. This study examined real-world PrEP clinical questions/cases from providers to a teleconsultation service to identify knowledge gaps and improve PrEP-related training materials and clinical guidelines. Methods: The National Clinician Consultation Center (NCCC) PrEPline provides educational teleconsultation services on clinical decision-making related to PrEP for U.S. health care providers. The NCCC PrEP consultation data collected between 2017 and 2020 were reviewed and systematically categorized by clinical topics, subtopics, and complexity levels (low, moderate, and high). Results: Within the study period, the PrEPline provided 1,754 teleconsultations. More than three quarters came from advanced practice nurses and physicians. The topics of questions commonly focused on medication-based HIV prevention strategies (22.7%), PrEP laboratory ordering/monitoring (17.4%), and side effects and contraindications (14.6%). The majority of teleconsultations (57.9%) involved sharing information that was directly available/addressed in the Centers for Disease Control and Prevention (CDC) 2017 PrEP Guidelines (i.e., low complexity). Discussion: The low frequency of consultations from nonphysician and non-nurse practitioner providers may suggest a need for increased training and collaborative opportunities for other types of providers. The high percentage of low-complexity inquiries may reveal a desire for capacity-building materials specifically designed for practicing providers (e.g., abridged versions of guidelines). This study may inform future research, best clinical practices, and aid in the development of training materials to increase providers' HIV prevention comfort and knowledge.

MTN-025/HOPE was an open-label trial of the dapivirine vaginal ring conducted in four African countries between 2016 and 2018. Women were first offered one ring monthly (at baseline, months 1 and 2), thereafter, transitioned to a more applicable real-world dispensation schedule, - 3 rings quarterly (at months 3, 6 and 9). Logistic regression analysis was used to assess correlates of ring acceptance at baseline and through follow-up. A total of 1456 women (median age 31 years) enrolled, 1342 (92.2%) accepted the ring at baseline and 1163 (79.9%) accepted the ring(s) at all visits. Changing ring dispensation from a monthly to a quarterly schedule had no negative effect on acceptance. Having a primary partner and him knowing about the ring being offered in HOPE, use of long-acting contraception (implants, injections, IUDs) or sterilization were associated with ring acceptance, along with prior strong intention to use the ring in the future. Efforts should consider these factors when rolling out the ring for HIV prevention., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: HIV disproportionally affects persons who inject drugs (PWID), but engagement with HIV pre-exposure prophylaxis (PrEP) is low. We describe the rationale and study design for a new study, "Contingency Management and Pre-Exposure Prophylaxis (PrEP) Adherence Support Services (CoMPASS)," a hybrid type 1 effectiveness-implementation trial to promote HIV risk reduction among PWID., Methods: In four community-based programs in the northeastern United States, PrEP-eligible PWID (target n = 526) are randomized to treatment as usual or Contingency Management (CM) and, as indicated, stepped up to PrEP Adherence Support Services (CoMPASS) over 24 weeks. During CM sessions, participants receive timely tangible rewards for verifiable activities demonstrating 1) PrEP initiation and adherence, and 2) engagement with medications for opioid use disorder (MOUD) and other OUD-related care. Participants who do not have high levels of biomarker-confirmed PrEP adherence at week 12 will be stepped up to receive PrEP Adherence Support Services (PASS) consisting of strengths-based case management over 12 weeks. Interventions are delivered by trained PrEP navigators, staff embedded within the respective sites. The primary outcome is sustained PrEP adherence by dried blood spot testing at 24 weeks. To inform future implementation, we are conducting implementation-focused process evaluations throughout the clinical trial., Conclusions: Results from this protocol are anticipated to yield novel findings regarding the impact and scalability of CoMPASS to promote HIV prevention among PWID in partnership with community-based organizations. http://ClinicalTrials.gov identifier: NCT04738825., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose. POC: Point of Care., (Published by Elsevier Inc.)

Background: Topical on-demand forms for HIV pre-exposure prophylaxis (PrEP) may be a desirable alternative for people that prefer not to use daily PrEP. CONRAD has developed inserts containing tenofovir alafenamide (TAF) and elvitegravir (EVG) for on-demand vaginal or rectal pericoital use. We assessed the pharmacokinetics (PK) and pre-exposure efficacy of rectally applied TAF/EVG inserts in macaques., Methods: PK was assessed in 12 pigtailed macaques. Tenofovir (TFV) and EVG levels were assayed in rectal biopsies and secretions, and tenofovir-diphosphate (TFV-DP) levels in biopsies and peripheral blood mononuclear cells (PBMC). Drug biodistribution was evaluated in 10 animals at necropsy 4 h post-dosing. For efficacy assessments, one or two TAF/EVG inserts were administered to macaques (n = 6) 4 h before repeated rectal SHIV162p3 challenges., Findings: One TAF/EVG insert resulted in rapid and high EVG and TFV-DP in rectal tissue 4 h after application. Adding a second insert led to a 10-fold increase in EVG and TFV-DP in rectal tissue. Efficacy of one and two TAF/EVG inserts were 72.6% (CI 24.5%-92.6%) and 93.1% (CI 73.3%-99.2%), respectively., Interpretation: Although high TFV-DP and EVG levels were observed with one rectal TAF/EVG insert, it only conferred partial protection from rectal SHIV challenges. Adding a second insert led to an increase in TFV and EVG in rectal tissues resulting in higher (>90%) efficacy. These results highlight the high efficacy of TAF/EVG inserts as topical on-demand rectal PrEP, as well as the need for appropriate drug coverage in the deep rectum and colon to achieve high protection., Funding: The work related to animal studies was funded by CDC intramural funds and an interagency agreement between CDC and USAID (USAID/CDC IAA AID-GH-T-15-00002). The work related to the insert formulation was funded by U.S. PEPFAR through USAID under a Cooperative Agreement (AID-OAA-A-14-00010) with CONRAD/Eastern Virginia Medical School. The findings and conclusions of this manuscript are those of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention (CDC), USAID, President's Emergency Plan for AIDS Relief (PEPFAR), Eastern Virginia Medical School (EVMS), or the US government., Competing Interests: Declaration of interests J.G.G-L and W.H. are named in the US. Government (USG) patents on “Inhibition of HIV infection through chemoprophylaxis” and “HIV post-exposure prophylaxis” and a patent application on “HIV pre-exposure prophylaxis”. W. H. and J. G. G.-L. report royalties or licenses from Mylan, Laurus Generics, TAD Pharma, and CIPLA Limited. M.M.P., V.A., G.F.D., and M.R.C. are named in patent applications on “Pharmaceutical compositions and methods of making on-demand solid dosage formulations,” inventions that were developed under US Agency for International Development (USAID)-funded cooperative agreement. N.M., T.S., J. M., A.H., C.D., M.M., Y.P., and J.M.S., declare no competing interest. The findings and conclusions of this manuscript are those of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention (CDC), USAID, President's Emergency Plan for AIDS Relief (PEPFAR), Eastern Virginia Medical School (EVMS), or the USG., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The global expansion of HIV pre-exposure prophylaxis (PrEP) includes health systems that face a shortage of skilled health care workers (HCWs). We estimated the human resource needs and costs for providing PrEP in nurse-led primary care clinics in Eswatini. Furthermore, we assessed potential cost savings from task sharing between nurses and other HCW cadres., Methods: We conducted a time-and-motion and costing study in a PrEP demonstration project between August 2017 and January 2019. A form for recording time and performed activities ("motion") was filled by HCWs of six primary care clinics. To estimate the human resource needs for specific PrEP activities, we allocated recorded times to performed PrEP activities using linear regression with and without adjusting for a workflow interruption, that is, if a client was seen by different HCWs or by the same HCW at different times. We assessed a base case in which a nurse provides all PrEP activities and five task shifting scenarios, of which four include workflow interruptions due to task sharing between different HCW cadres., Results: On average, PrEP initiation required 29 min (95% CI 25-32) of HCW time and PrEP follow-up 16 min (95% CI 14-18). The HCW time cost $4.55 (uncertainty interval [UI] 1.52-9.69) for PrEP initiation and $2.54 (UI 1.07-4.64) for PrEP follow-up when all activities were performed by a nurse. Time costs were $2.30-4.25 (UI 0.62-9.19) for PrEP initiation and $1.06-2.60 (UI 0.30-5.44) for PrEP follow-up when nurses shared tasks with HCWs from lower cadres. Interruptions of the workflow added, on average, 3.4 min (95% CI 0.69-6.0) to the time HCWs needed for a given number of PrEP activities. The cost of an interrupted workflow was estimated at $0.048-0.87 (UI 0.0098-1.63) depending on whose time need increased., Conclusions: A global shortage of skilled HCWs could slow the expansion of PrEP. Task shifting to lower-cadre HCW in nurse-led PrEP provision can free up nurse time and reduce the cost of PrEP provision even if interruptions associated with task sharing increase the overall human resource need., (© 2022. The Author(s).)

Shared decision making is a collaborative process intended to develop a treatment plan that considers both the patient's preferences and the health provider's medical recommendations. It is one approach to reducing healthcare disparities by improving patient-provider communication and subsequent health outcomes. This study examines shared decision making about HIV pre-exposure prophylaxis (PrEP) with Black transgender women in Chicago, Illinois, USA, given high prevalence of HIV and disparities in PrEP use. Black transgender women were recruited online and in-person to participate in semi-structured interviews ( n  = 24) and focus groups (2; n  = 14 total), conducted between 2016 and 2017. Iterative thematic content analysis took place. Analysis revealed that internalised transphobia and racism, combined with stigma from service providers, prevented disclosure of gender and sexual identity to providers. Stigma about PrEP as it relates to Black transgender women results in stereotype threat, which undermines patient-provider trust and deters shared decision making for PrEP. Shared decision making promotes cultural competence and humility and builds trust within the patient-provider relationship, leading to better communication and less stigma. The involvement of peers may be one way to mitigate stigma for Black transgender women around PrEP, promote cultural competence within organisations, and empower engagement in shared decision making for HIV prevention.

HIV pre-exposure prophylaxis (PrEP) has shown high efficacy and effectiveness for HIV prevention; however, many individuals with PrEP indications are not receiving PrEP. PrEP Coordinators work closely with patients and health care providers to increase PrEP access, and they provide unique insights into the inner workings of PrEP care and service delivery. In this study, we discuss key challenges and recommendations for improved PrEP service delivery (including training PrEP Coordinators to manage PrEP panels, making PrEP a part of routine care and optimizing electronic health records, designating a PrEP "champion" who can strengthen communication and leadership, using a proactive approach to increase PrEP retention, and training providers and PrEP Coordinators to meet youth-specific needs) from our discussions with the PrEP Coordinators who led PrEP panel management in San Francisco Department of Public Health primary care clinics.

The DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored, Safe) Initiative works to reduce HIV infection among adolescent girls and young women (AGYW) through prevention interventions including Pre-Exposure Prophylaxis (PrEP). Pamoja CBO in Kisumu, Kenya implemented DREAMS. We describe PrEP initiation and persistence in 549 AGYW who started PrEP through Pamoja and factors associated with discontinuation. Median persistence time was 308 days (95% CI 245, 382) with 59% of AGYW discontinuing by the end of the study. The most common reasons for stopping PrEP were lack of perceived risk (27.9%) and relocation (18.7%). In the multivariable model, only age < 18 was associated with stopping PrEP. Younger age was associated with shorter time to discontinuation. Implementing PrEP through DREAMS was successful in supporting initiation of PrEP for AGYW. However, low rates of persistence at 1 year emphasizes the need for strategies to support PrEP persistence if HIV elimination is to be achieved., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite growing availability, HIV pre-exposure prophylaxis (PrEP) uptake and adherence remains suboptimal among female sex workers (FSW) in the United States. Using cross-sectional data from a survey of 236 street-based cisgender FSW in Baltimore, Maryland, we examined interest in event-driven and long-acting PrEP formulations. Latent class analysis identified discrete patterns of interest in five novel PrEP agents. Multinomial latent class regression then examined factors associated with probabilistic class membership. A three-class solution emerged as the best-fit latent class model: Injectable Acceptors (~ 24% of sample), Universal Acceptors (~ 18%), and Non-Acceptors (~ 58%). Compared to Non-Acceptors, Universal Acceptors had significantly (p < 0.05) higher odds of reporting condomless vaginal sex with clients, client condom coercion, and client-perpetrated physical violence. Relative to Non-Acceptors, Injectable Acceptors were distinguished by significantly higher rates of condomless vaginal sex with clients and injection drug use. Expanding PrEP options for FSW could help overcome barriers to PrEP initiation and persistence., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The objective was to perform a survey-based service evaluation of our telephone PrEP clinic (Tele-PrEP), which was instituted during the COVID-19 pandemic, to inform future service delivery., Methods: We administered parallel, web-based, anonymous surveys to PrEP-users who had a Tele-PrEP appointment between 13.11.2020 and 17.12.2020 and all healthcare professionals (HCPs) conducting Tele-PrEP clinics. We used descriptive statistics to summarise demographic and qualitative data, and thematically categorised free text responses using the Framework for a Systems Approach to Healthcare Delivery., Results: 62/117 (53%) PrEP-users and 8/9 (89%) HCPs completed the surveys. Tele-PrEP was rated 'excellent' or 'good' by 61/62 (98%) PrEP-users. All HCPs felt that Tele-PrEP allowed them to assess patients safely and confidently. 10/62 (16%) PrEP-users and 1 (11%) HCP expressed a preference for face-to-face care. Using the Framework for a Systems Approach to Healthcare Delivery we identified key areas important to respondents who highlighted the rapid changes as a result of COVID-19, which required an increase in dedicated resources. HCPs valued teamwork, support/supervision and convenience in achieving quality care for the patient, who in turn, valued convenient, holistic and individualised management to meet their sexual healthcare needs., Conclusion: Tele-PrEP is feasible and acceptable. While most respondents rated the service highly, others identified a need/preference for face-to-face appointments.

In August 2021, a man who has sex with men was diagnosed with HIV-1 infection despite using event-driven pre-exposure prophylaxis for over 2 years with self-reported excellent adherence. Sequencing identified resistance-associated mutations (RAM) M184V and K65R, conferring resistance to emtricitabine and tenofovir, and RAM V108I and E138A. Background RAM prevalence was two of 164 (1.2%) new HIV diagnoses in Amsterdam (2017-19). We reiterate the need for frequent HIV testing among PrEP users and additional testing in case of symptoms.

Background: Underutilization of HIV pre-exposure prophylaxis (PrEP) in the Southern United States (US) is well-documented. Urgent care (UC) centers are positioned as communityfacing access points to PrEP, but the feasibility of integrating PrEP services into this setting is unclear. We conducted a survey of UC clinicians in the Southern US to better understand their perceptions of the feasibility of providing PrEP in their practice setting., Objective: The study aims to determine the feasibility and acceptability of providing PrEP services in the UC setting through a cross-sectional survey of UC clinicians., Methods: We conducted a 48-item cross-sectional survey of UC clinicians in the Southern US, between July and September 2020. The survey was distributed through the Urgent Care Association (UCA) and American Academy of Urgent Care Medicine (AAUCM) professional listservs as well as directly to publicly listed e-mail addresses., Results: Eighty-two clinicians responded to the survey. Most clinicians had familiarity with PrEP (97%). All respondents rated PrEP as an effective way to prevent HIV. However, less than half felt UC facilities were an appropriate place to prescribe PrEP. Few respondents (8%) expressed doubts that expansion of PrEP access would decrease the incidence of HIV in their community., Conclusion: These findings show UC clinicians are familiar with PrEP, and many believe it would benefit their patients; however, provider opinions on the appropriateness of providing PrEP in the UC setting differ. Further studies on PrEP implementation in UC centers are needed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Black adolescent girls and young women (AGYW) are disproportionately affected by HIV in the southern U.S.; however, PrEP prescriptions to Black AGYW remain scarce. We conducted in-depth interviews (IDIs) with Black AGYW ages 14-24 in Alabama to explore opportunities for and barriers to sexual health care including PrEP prescription. Twelve AGYW participated in IDIs with median age 20 (range 19-24). All reported condomless sex, 1-3 sexual partners in the past 3 months, and 6 reported prior STI. Themes included: 1) Stigma related to sex contributes to inadequate discussions with educators, healthcare providers, and parents about sexual health; 2) Intersecting stigmas around race and gender impact Black women's care-seeking behavior; 3) Many AGYW are aware of PrEP but don't perceive it as an option for them. Multifaceted interventions utilizing the perspectives, voices, and experiences of Black cisgender AGYW are needed to curb the HIV epidemic in Alabama and the U.S. South.

Introduction: Evidence indicates HIV oral pre-exposure prophylaxis (PrEP) is highly efficacious and effective. Substantial early discontinuation rates are reported by many programs, which may be misconstrued as program failure. However, PrEP use may be non-continuous and still effective, since HIV risk fluctuates. Real-world PrEP use phenomena, like restarting and cyclical use, and the temporal characteristics of these use patterns are not well described. The objective of our study was to characterize and identify predictors of use patterns observed in large PrEP scale-up programs in Africa., Methods: We analysed demographic and clinical data routinely collected during client visits between 2017 and 2019 in three Jhpiego-supported programs in Kenya, Lesotho and Tanzania. We characterized duration on/off PrEP and, using ordinal regression, modelled the likelihood of spending additional time off and identified factors associated with increasing cycle number. The Andersen-Gill model was used to identify predictors of time to PrEP discontinuation. To analyse factors associated with a client's first return following initiation, we used a two-step Heckman probit., Results: Among 47,532 clients initiating PrEP, approximately half returned for follow-up. With each increase in cycle number, time off PrEP between use cycles decreased. The Heckman first-step model showed an increased probability of returning versus not by older age groups and among key and vulnerable population groups versus the general population; in the second-step model older age groups and key and vulnerable populations were less likely in Kenya, but more likely in Lesotho, to return on-time (refill) versus delayed (restarting)., Conclusions: PrEP users frequently cycle on and off PrEP. Early discontinuation and delays in obtaining additional prescriptions were common, with broad predictive variability noted. Time off PrEP decreased with cycle number in all countries, suggesting normalization of use with experience. More nuanced measures of use are needed than exist for HIV treatment if effective use of PrEP is to be meaningfully measured. Providers should be equipped with measures and counselling messages that recognize non-continuous and cyclical use patterns so that clients are supported to align fluctuating risk and use, and can readily restart PrEP after stopping, in effect empowering them further to make their own prevention choices., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Competing Interests: Competing interests: None declared.

Background: While the introduction of HIV Pre-Exposure Prophylaxis (PrEP) as an HIV prevention strategy has allowed women to exercise more control over the reduction of HIV transmission rates, adolescent girls and young women in Sub-Saharan Africa continue to experience higher rates of HIV infections and bear the greatest disease burden. Understanding progress in PrEP uptake among adolescent girls and young women would enhance risk reduction in this vulnerable population. The Determined, Resilient, AIDS-Free, Mentored and Safe women (DREAMS) Initiative plays a key role in this risk reduction strategy., Methods: We performed a qualitative study to explore facilitators and barriers to PrEP implementation and assess factors effecting initiation and persistence on PrEP among adolescent girls and young women enrolled in the DREAMS Initiative at Pamoja Community Based Organization in Kisumu, Kenya. We conducted key informant interviews (n = 15) with Pamoja Community Based Organization staff, health care providers and community leaders. Additionally, we conducted focus group discussions with young women receiving PrEP and peer mentors (n = 40). We performed a directed content analysis using the Consolidated Framework for Implementation Research to organize the identified facilitators and barriers., Results: We found that the use of the safe space model, decentralization of PrEP support and delivery, peer mentors, effective linkage to local health care facilities, the sensitization of parents and male sexual partners, disclosure of PrEP use by beneficiaries, active stakeholder involvement and community engagement were among some of the facilitators to PrEP uptake. Barriers to PrEP implementation, initiation and persistence included stigma associated with the use of anti-retroviral drugs, drug side effects, frequent relocation of beneficiaries, limited resources for routine screening and medication monitoring, and a limited number of qualified health care workers for PrEP distribution and administration., Conclusion: Overall, the community roll-out of PrEP within the DREAMS Initiative was successful due to a number of key facilitating factors, which ultimately led to successful PrEP implementation, increased PrEP initiation and enhanced persistence among adolescent girls and young women. The identified barriers should be addressed so that a larger scale-up of PrEP roll-out is possible in the future.

While HIV infections among men who have sex men (MSM) have started to decline in the United States, Black MSM continue to experience disproportionate rates of HIV infection. The purpose of this secondary analysis is to examine risk perception and its influence on PrEP adherence among Black MSM from HPTN 073. Risk perception was measured using the adapted Perceived Vulnerability to HIV Scale. The associations between risk perception and PrEP adherence were tested using generalized estimation equation model for time-variant repeated measures. Risk perception was not significantly associated with PrEP adherence. These findings suggest an there was no risk compensation among PrEP users, and inconsistency in perceived risk for HIV. Future studies should investigate the rationale for long term adherence to PrEP among Black MSM.

Background: Adult women account for >19% of all new HIV diagnoses in the United States, but receive only 7%-8% of new prescriptions for HIV pre-exposure prophylaxis (PrEP), and report low awareness of PrEP even within communities with high risk of HIV transmission. Family planning (FP) programs are a promising, underutilized setting for the provision of PrEP counseling to women, especially the 40% of women FP clients who receive no other form of health care. This study tested the feasibility of integrating routine PrEP counseling in a high-volume FP clinic with no previous PrEP experience. Materials and Methods: Trained FP counselors at a FP clinic in Philadelphia surveyed women about knowledge and attitudes related to PrEP, then provided a brief PrEP counseling intervention. After counseling, knowledge and attitudes were reassessed. In response to counselor requests, we developed the Women's PrEP Counseling Checklist (WPCC) tool to structure and standardize each counseling session. We then compared baseline and postintervention data among participants overall and in two cohorts: those receiving unguided counseling (initial design) and those receiving WPCC-guided counseling (enhanced design). Results: Both cohorts displayed significant ( p  < 0.0001) gains in PrEP knowledge and acceptability after counseling. Participants receiving WPCC-guided counseling reported higher knowledge scores postintervention ( p  = 0.031) and greater gains in PrEP acceptability ( p  = 0.000) than their peers receiving unguided counseling. Conclusions: Introducing PrEP counseling into routine FP care is feasible, and effectively improves knowledge and attitudes about PrEP within a large population of women, broadening access to PrEP on individual and population levels. The WPCC tool both enhances the impact of counseling on patients and reduces the work burden on providers.

Introduction: HIV incidence remains high among African adolescent girls and young women (AGYW), who would benefit from pre-exposure prophylaxis (PrEP). Strategies to increase PrEP adherence and persistence need to be evaluated in African AGY, including incentives conditional on high adherence., Methods: The 3Ps for Prevention Study was a 12-month prospective cohort of 200 women ages 16 to 25 initiating PrEP in South Africa from 2017 to 2018. Participants received retrospective feedback about drug levels at Months 1, 2 and 3; half was randomized to receive a 200 Rand shopping voucher ($13 US) at Months 2, 3 and 4, conditioned on high intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots (≥500 fmol/punch at Month 1, ≥700 fmol/punch at Months 2 and 3). The primary analysis was intention-to-treat, comparing the proportion with high PrEP adherence (≥700 fmol/punch) at Month 3 by randomized group, based on 100% efficacy among men who have sex with men., Results: Median age of the 200 women was 19 years (interquartile range [IQR] 17, 21); 86% had a primary sexual partner. At Month 3, the mean TFV-DP level was 822 fmol/punch (SD 522) in the incentive group and 689 fmol/punch (SD 546) in the control group (p = 0.11). Forty-five (56%) of 85 women in the incentive group and 35 (41%) of 85 women in the control group had TFV-DP levels ≥700 fmol/punch (RR 1.35; 95% CI 0.98, 1.86; p = 0.067), which declined to 8% and 5% in the incentive and control groups at Month 12 (no significant difference by arm). 44% refilled PrEP without gaps, 14% had a gap of ≥3 weeks in coverage subsequently restarted PrEP and 54% accepted at the final dispensing visit at Month 9. No new HIV infections were observed after PrEP initiation., Conclusions: Among South African AGYW initiating PrEP, drug levels indicated high PrEP adherence in almost half of women at Month 3, with a non-statistically significant higher proportion with high adherence among those in the incentive group. Over half persisted with the 12-month PrEP programme although high adherence declined after Month 3. Strategies to support PrEP adherence and persistence and longer-acting PrEP formulations are needed., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: Tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) is used for HIV pre-exposure prophylaxis (PrEP). TDF may affect bone mineral density (BMD), particularly in youth who are at a stage of peak bone mass accrual. The objective of this study was to evaluate the effect of vitamin D and calcium supplementation on BMD among Thai youth receiving daily oral PrEP., Methods: This open-label randomized trial was conducted in male youth aged between 15 and 24 years. Participants were randomized to Arm A who received once-daily TDF/FTC plus vitamin D3 and calcium supplementation with meals twice daily (400 units of vitamin D3 and 1200 mg of elemental calcium/day) or Arm B who received once-daily TDF/FTC only. PrEP users were defined as taking at least two tablets/week (tenofovir-diphosphate level of >350 fmol/punch). Adherence to vitamin D/calcium supplementation was defined as self-reported adherence of >50%. Lumbar spine (L2-L4) BMD (LSBMD) was evaluated by dual-energy X-ray absorptiometry scan zero and six months after PrEP initiation., Results: From March 2019 to March 2020, 100 youth were enrolled. Baseline characteristics between the two arms were similar. Median (IQR) age was 18 (17 to 20) years. At entry, median (IQR) LSBMD z-score was -0.8 (-1.5 to -0.3), 17% had low LSBMD (Z-score < -2). The median amount of calcium intake from nutritional three-day recall was 167 (IQR 94 to 272) mg/day, 39% of participants had vitamin D deficiency, defined as 25(OH)D levels <20 IU/mL. At six months, 79 participants were evaluated. Of these, 42 (52%) were PrEP takers and 25 of 38 (66%) of arm A participants had good adherence to vitamin D/calcium supplementation. Significantly higher proportions of youth in arm A compared to arm B had >3% increase in LSBMD at month 6 compared to baseline (67.6% vs. 42.9% respectively; p = 0.03). There were significantly higher increases in LSBMD among youth with vitamin D deficiency who were supplemented; arm A + 0.05 (0 to 0.05) compared to arm B + 0.03 (-0.1 to 0.03), p = 0.04., Conclusions: Increases in LSBMD over six months among youth using PrEP who received vitamin D/calcium supplementation was greater than those not supplemented. Long-term follow-up should be considered to explore long-term outcomes., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objectives: Recent evidence shows that patients using HIV pre-exposure prophylaxis (PrEP) have an increased rate of bacterial STIs, including syphilis, chlamydia and gonorrhoea. Our study aimed to describe the acquisition and the susceptibility for macrolides of Mycoplasma genitalium in men who have sex with men (MSM) on PrEP., Methods: We studied all MSM who started PrEP in the AZ Sint-Jan Hospital Bruges from 1 June 2017 to 31 March 2019 with at least one follow-up visit. Patients were screened for M. genitalium and other STIs with pooled rectal swabs, pharyngeal swabs and first-voided urine, and blood samples at baseline and quarterly intervals after initiating PrEP. TaqMan Array Card technology was used to detect M. genitalium and determine macrolide-resistance mediating mutations in region V of the 23S rRNA gene (A2058G, A2059G, A2058C and others). Patients with an STI were treated based on a national guideline., Results: 131 MSM (median age 40 years, range 20-79) were included in the study. The median follow-up time was 12 months (IQR 6.1-17). Baseline prevalence of M. genitalium was 6.9% and incidence rate after PrEP initiation was 28.8 per 100 person-years (95% CI 21.7 to 37.2), without significant differences in proportions between the first four quarterly intervals. All but one acquisitions were asymptomatic. Younger age and positivity for M. genitalium at baseline were significantly associated with incident M. genitalium acquisition. The observed proportion of macrolide resistance increased not significantly from 44% at baseline to 57%-86% after PrEP initiation. None of the 27 macrolide-resistant M. genitalium acquisitions could be linked to azithromycin exposure in the three preceding months., Conclusions: After initiation of PrEP, we found a stable incidence of almost exclusively asymptomatic M. genitalium . However, a non-significant trend of an increased percentage of macrolide-resistant strains was observed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Various disparities exist in HIV transmission among men who have sex with men (MSM). Pre-exposure prophylaxis (PrEP) has been shown to decrease the acquisition of HIV, but there is variation in uptake within the MSM population. We aim to characterise PrEP use and correlates of self-reported PrEP use in a large national sample of urban MSM in the USA., Methods: Using data from a geosocial-networking application, a national sample (n=3744) from the largest 50 metropolitan centres in the USA was obtained., Results: We found 18.1% (95% CI 16.8 to 19.3) of profiles reported using PrEP, with decreased reported PrEP use in younger MSM aged 18-24 years (adjusted OR (aOR)=0.5, 95% CI 0.3 to 0.7), obese MSM (aOR=0.5, 95% CI 0.3 to 0.9), black MSM (aOR=0.6, 95% CI 0.4 to 0.9) and MSM in the South (aOR=0.7, 95% CI 0.5 to 0.9)., Conclusion: Significant disparities exist in PrEP reporting by age and among black, Southern US and obese MSM. More research is needed to better understand these disparities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite being a promising prevention strategy for populations at risk for HIV acquisition, there has not been rapid uptake of HIV antiretroviral pre-exposure prophylaxis (PrEP). Yet, HIV clinics within the Mount Sinai Health System in New York City have successfully incorporated PrEP. HIV care providers ( n  = 18), who practice in these clinics and were early PrEP adopters, participated in a survey and semistructured interview. Qualitative thematic analysis revealed that barriers and facilitators to PrEP uptake were identified on multiple levels from broader systemic to provider-and-patient-level concerns. The following themes were identified: (1) to reach a greater proportion of patients at risk for HIV and address racial/ethnic and gender disparities, PrEP should be available in a variety of settings and provided by different types of providers within proximity to affected populations; (2) financial support is needed beyond addressing medication cost; and (3) multidisciplinary teams and population-specific clinic protocols can assist providers in conducting high-quality visits and addressing these barriers to PrEP.

Introduction: Among men who have sex with men (MSM) and transgender women (TW), stimulant use is high and has been associated with an increased risk of HIV infection, suicide and cardiovascular disease (CVD) mortality. We used epidemic modelling to investigate these intersecting health harms among MSM/TW in Lima, Peru and assess whether they could be mitigated by prioritizing HIV pre-exposure prophylaxis (PrEP) and harm reduction interventions among MSM/TW who use stimulants., Methods: We adapted a dynamic model of HIV transmission among MSM/TW in Lima to incorporate stimulant use and increased HIV risk, suicide and CVD mortality. Among 6% to 24% of MSM/TW using stimulants (mostly cocaine), we modelled an increased risk of unprotected anal sex (RR = 1.35 [95%CI: 1.17 to 1.57]) obtained from local data, and increased risk of suicide (SMR = 6.26 [95%CI: 2.84 to 13.80]) and CVD (SMR = 1.83 [95%CI: 0.39 to 8.57]) mortality associated with cocaine use based on a global systematic review. We estimated the proportion of health harms occurring among MSM/TW who use stimulants in the next year (01-2020/01-2021). We also investigated the 10-year impact (01-2020/01-2030) of: (1) PrEP prioritization for stimulant-using MSM/TW compared to random allocation, and (2) integrating PrEP with a theoretical intervention halving stimulant-associated risk., Results: MSM/TW in Lima will experience high HIV incidence, suicide mortality and CVD mortality (1.6/100 py, and 0.018/100 py, 0.13/100 py respectively) in 2020. Despite stimulant using MSM/TW comprising an estimated 9.5% (95%CI: 7.8 to 11.5) of all MSM/TW, in the next year, 11% 95%CI (i.e. 2.5% to 97.5% percentile) 10% to 13%) of new HIV infections, 39% (95%CI: 18% to 60%) of suicides and 15% (95%CI: 3% to 44%) of CVD deaths could occur among this group. Scaling up PrEP among all stimulant using MSM/TW could prevent 19% (95%CI: 11% to 31%) more HIV infections over 10 years compared to random allocation. Integrating PrEP and an intervention to halve stimulant-associated risks could reduce new HIV infections by 20% (95%CI: 10% to 37%), suicide deaths by 14% (95%CI: 5% to 27%) and CVD deaths by 3% (95%CI: 0% to 16%) over a decade., Conclusions: MSM/TW who use stimulants experience a disproportionate burden of health harms. Prioritizing PrEP based on stimulant use, in addition to sexual behaviour/gender identity criteria, could increase its impact. Integrated substance use, harm reduction, mental health and HIV care among MSM/TW is needed., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Purpose: Sexual transmission of HIV has been clinically proven to be preventable with a once-daily oral tablet; however, missed doses dramatically increase the risk of HIV infection. Long-acting subcutaneous implants do not allow the user to miss a dose. A desirable long-acting drug-eluting implant can deliver a constant amount of drug, adjust the delivered dose, and be readily manufactured. We present a long-acting, subcutaneous implant design composed of tenofovir alafenamide hemifumarate (TAF) pellets loaded in a sealed polyether urethane tube for the prevention of HIV transmission., Methods: Implants were prepared with pressed drug pellets and extruded polyurethane tubing. In vitro release rate of implants using different pellet formulations, rate-controlling membranes, and geometries were measured., Results: Tenofovir alafenamide release appeared to be governed by a pseudo-steady state and followed a mass transport model of release from a cylindrical drug reservoir. Implant seal integrity was tested and confirmed using mechanical testing. The inclusion of sodium chloride in the pellet increased the release rate and reduced initial lag. The release was sustained for 100 days., Conclusions: The release rate of tenofovir alafenamide mechanistically varied with geometry and rate controlling membrane composition. The polyether urethane implant presented herein is modular and tunable to adjust the release rate and duration of the TAF release.

Purpose: Pre-exposure prophylaxis (PrEP) is a pillar of the US Department of Health and Human Services "Ending the HIV Epidemic" (EHE) initiative in 50 EHE jurisdictions (48 U.S. counties and two U.S. cities) and seven U.S. states with high numbers of HIV diagnoses rates in rural areas. Current data systems do not provide data on PrEP uptake in counties or cities., Methods: We report on PrEP users at the county level. Data from a large, commercial pharmacy database were used; we applied the U.S. Census Bureau's method to allocate PrEP users within a ZIP3 into counties and validated the results. We report counts and rates of PrEP users in 2018 for all EHE jurisdictions. We used joinpoint regression to model the estimated annual percent change in PrEP use for each jurisdiction and state., Results: 93,156 people in the 50 EHE jurisdictions used PrEP in 2018; 94% were men and 39% were aged 25-34 years. There was more than an 80-fold difference in the range of rates of PrEP use per 100,000 population among the EHE jurisdictions (range: 8-644 per 100,000 population; median 93 per 100,000 population). PrEP use increased from 2012 to 2018 in all EHE counties and states. At current rates of growth of PrEP use, 94% of EHE counties and jurisdictions will reach their National HIV/AIDS Strategy goals of a 500% increase in PrEP use in 2020. EHE states had less variation in rates of PrEP use (range: 29-51/100,000 population; median 32/100,000 population)., Conclusions: At the outset of a major U.S. government program to reduce HIV infections, rates of PrEP use are highly variable among the 50 EHE jurisdictions. Data from commercial prescription databases will be a useful public resource to understand progress in promoting use of PrEP as part of the EHE initiative and evaluating progress in PrEP use across health jurisdictions., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Pre-exposure prophylaxis (PrEP) is an effective tool for preventing HIV infection among men who have sex with men (MSM), but its cost-effectiveness has varied across settings. Using an agent-based model, we projected the cost-effectiveness of a statewide PrEP program for MSM in Rhode Island over the next decade. In the absence of PrEP, the model predicted an average of 830 new HIV infections over ten years. Scaling up the existing PrEP program to cover 15% of MSM with ten or more partners each year could reduce the number of new HIV infections by 33.1% at a cost of $184,234 per quality-adjusted life-year (QALY) gained. Expanded PrEP use among MSM at high risk for HIV infection has the potential to prevent a large number of new HIV infections but the high drug-related costs may limit the cost-effectiveness of this intervention.

Uptake of pre-exposure prophylaxis (PrEP) has been limited among black and Latino men who have sex with men (MSM), especially in the southern United States. Public health departments and federally qualified health centers (FQHCs) serving predominantly uninsured populations are uniquely positioned to improve access. We evaluated a novel PrEP collaboration between a public health department and an FQHC in North Carolina (NC). In May 2015, a PrEP program was initiated that included no-cost HIV/sexually transmitted infection screening at a public health department, followed by referral to a colocated FQHC for PrEP services. We profiled the PrEP continuum for patients entering the program until February 2018. PrEP initiators and noninitiators were compared using Wilcoxon rank-sum test for continuous variables and chi-square or Fisher's exact tests for categorical variables. Of 196 patients referred to the FQHC, 60% attended an initial appointment, 43% filled a prescription, 38% persisted in care for >3 months, and 30% reported >90% adherence at follow-up. Among those presenting for initial appointments ( n  = 117), most were MSM ( n  = 95, 81%) and black ( n  = 62, 53%); 21 (18%) were Latinx and 9 (8%) were trans persons. Almost half ( n  = 55) were uninsured. We found statistically significant differences between PrEP initiators versus noninitiators based on race/ethnicity ( p  = 0.02), insurance status ( p  = 0.05), and history of sex work ( p  = 0.05). In conclusion, this collaborative model of PrEP care was able to reach predominantly black and Latino MSM in the southern United States. Although sustainable, program strategies to improve steps along the PrEP care continuum are vital in this population.

Implants are in the pre-clinical stage for long-acting HIV pre-exposure prophylaxis (PrEP), with an opportunity to solicit end-users' feedback early in development. Health care providers (HCPs) have been key gatekeepers for contraceptive implant uptake, and uniquely understand both technical considerations and the social context of use. Given their influential role, we gathered South African HCP perspectives on contraceptive implant implementation and features of PrEP implant prototypes that may influence future provider and patient acceptability. We conducted in-depth interviews with 30 HCPs (20 nurses and 10 doctors) in Cape Town and Soshanguve, South Africa. Interviews were conducted by a bioengineer and later transcribed, coded, and analyzed for key themes. HCPs described health system barriers such as understaffed clinics and inadequate training on contraceptive implant removal as major influences to their PrEP implant design preferences. They preferred a PrEP implant that is long lasting (>6 months) to minimize patient-clinic interactions, biodegradable to avoid need for removal, and flexible (but still palpable in case of removal). Commenting on negative experiences with contraceptive implant rollout, they recommended prioritizing both HCP and community education on the PrEP implant, with emphasis on expected side effects, and planning ahead for adequate training of HCPs before rollout. Challenges experienced with past contraceptive implant rollout may taint perspectives on future PrEP implants and must be carefully considered during product development and planning for clinical studies. Particular consideration should be given to the health system context of future distribution, including staff who would be providing and monitoring implants.

We examined associations of 25-hydroxy vitamin D (25-OHD), tenofovir disoproxil fumarate (TDF), and bone toxicity. We studied TDF/emtricitabine (FTC) HIV pre-exposure prophylaxis (PrEP) in young men who have sex with men (YMSM). Bone toxicity was predefined using bone mineral density/content change from baseline to week 48. Baseline serum 25-OHD was dichotomized as <20 ng/mL (insufficient/deficient) versus ≥20 (sufficient), and week 48 dried blood spot tenofovir diphosphate (TFV-DP) as >700 fmol/punch (protective against HIV acquisition) versus ≤700. Associations were examined by univariate and multivariable logistic regression, reporting crude and adjusted odds ratios (ORs), with 95% confidence intervals (CIs). Of 101 enrolled, 69 had complete bone assessments and 25-OHD; of these, 59 had week 48 TFV-DP data. Median (Q1-Q3) age was 20 (18-21) years; 54% were black/African American. In univariate analysis, participants with baseline 25-OHD <20 ng/mL (OR = 5.4; 95% CI = 1.9-16.5) and blacks (OR = 4.9; 95% CI = 1.7-15.2) had greater odds of bone toxicity than those with 25-OHD ≥20 or other races. TFV-DP was not associated with bone toxicity (OR = 1.6; 95% CI = 0.5-5.5). In multivariable analysis, compared with those with 25-OHD ≥20 and TFV-DP ≤700, those with 25-OHD ≥20 and TFV-DP >700 (OR = 11.5; 95% CI = 1.4-169.6), 25-OHD <20 and TFV-DP ≤700 (OR = 19.4; 95% CI = 3.0-228.7), and 25-OHD <20 and TFV-DP >700 (OR = 32.3; 95% CI = 3.3-653.6) had greater odds of bone toxicity after adjusting for race. In multivariable models, 25-OHD insufficiency, protective TFV-DP concentrations, and black race were significantly associated with bone toxicity after 48 weeks of TDF/FTC PrEP in YMSM. Clinical Trials Registration: NCT01769469.

Aims: To explore the factors that position nurse practitioners (NPs) to lead the implementation of HIV pre-exposure prophylaxis., Background: The HIV epidemic represents a global health crisis. Reducing new HIV infections is a public health priority, especially for Black and Latino men who have sex with men (MSM). When taken as directed, co-formulated emtricitabine and tenofovir have over 95% efficacy in preventing HIV; however, substantial gaps remain between those who would benefit from pre-exposure prophylaxis (PrEP) and current PrEP prescribing practices., Design: This is a position paper that draws on concurrent assessments of research literature and advanced practice nursing frameworks., Method: The arguments in this paper are grounded in the current literature on HIV PrEP implementation and evidence of the added value of nurse-based models in promoting health outcomes. The American Association of Colleges of Nursing's advanced nursing practice competencies were also included as a source of data for identifying and cross-referencing NP assets that align with HIV PrEP care continuum outcomes., Conclusions: There are four main evidence-based arguments that can be used to advance policy-level and practice-level changes that harness the assets of nurse practitioners in accelerating the scale-up of HIV PrEP., Relevance to Clinical Practice: Global public health goals for HIV prevention cannot be achieved without the broader adoption of PrEP as a prevention practice among healthcare providers. NPs are the best hope for closing this gap in access for the populations that are most vulnerable to HIV infection., (© 2018 John Wiley & Sons Ltd.)

Purpose: Pre-exposure prophylaxis (PrEP) is an effective strategy to prevent HIV. However, low uptake of daily oral PrEP since Food and Drug Administration approval and low medication adherence among users have stimulated the investigation of other modalities for delivery, such as injectable PrEP and on-demand PrEP. The objective of this study was to determine the demographic and behavioral predictors of willingness to try alternative PrEP delivery mechanisms among young men who have sex with men (YMSM) who stated that they were unwilling to try daily oral PrEP., Methods: YMSM in California were recruited through geosocial networking applications; we analyzed a subsample who stated that they were either ambivalent about trying or unwilling to try daily oral PrEP (n = 265). We used chi-square and Fisher's exact tests to determine characteristics associated with willingness to try injectable PrEP, willingness to try on-demand PrEP, and willingness to try either alternative form., Results: For individuals who stated that they would not be willing to try daily oral PrEP, ∼85% were willing to try on-demand and/or injectable PrEP. Individuals who reported some college or more reported greater willingness to try injectable PrEP (adjusted odds ratio [aOR]: 2.92; 95% confidence interval [CI]: 1.32-6.46), on-demand PrEP (aOR: 2.28; 95% CI: 1.06-4.90), or either method (aOR: 5.54; 95% CI: 1.78-17.22)., Conclusion: Future research should determine how to enhance uptake of emerging forms of PrEP among the individuals most at risk for HIV.

Background: Gay, bisexual and other men who have sex with men (gbMSM) in Canada continue to experience high rates of incident HIV. Pre-exposure prophylaxis (PrEP, the regular use of anti-HIV medication) reduces HIV acquisition and could reduce incidence. However, there are too few physicians with expertise in HIV care to meet the projected demand for PrEP. To meet demand and achieve greater public health impact, PrEP delivery could be 'decentralized' by incorporating it into front-line prevention services provided by family physicians (FPs) and sexual health clinic nurses., Methods: This PrEP decentralization project will use two strategies. The first is an innovative knowledge dissemination approach called 'Patient-Initiated CME' (PICME), which aims to empower individuals to connect their family doctors with online, evidence-based, continuing medical education (CME) on PrEP. After learning about the project through community agencies or social/sexual networking applications, gbMSM interested in PrEP will use a uniquely coded card to access an online information module that includes coaching on how to discuss their HIV risk with their FP. They can provide their physician a link to the accredited CME module using the same card. The second strategy involves a pilot implementation program, in which gbMSM who do not have a FP may bring the card to designated sexual health clinics where trained nurses can deliver PrEP under a medical directive. These approaches will be evaluated through quantitative and qualitative methods, including: questionnaires administered to patients and physicians at baseline and at six months; focus groups with patients, FPs, and sexual health clinic staff; and review of sexual health clinic charts. The primary objective is to quantify the uptake of PrEP achieved using each decentralization strategy. Secondary objectives include a) characterizing barriers and facilitators to PrEP uptake for each strategy, b) assessing fidelity to core components of PrEP delivery within each strategy, c) measuring patient-reported outcomes including satisfaction with clinician-patient relationships, and d) conducting a preliminary costing analysis., Discussion: This study will assess the feasibility of a novel strategy for disseminating knowledge about evidence-based clinical interventions, and inform future strategies for scale-up of an underutilized HIV prevention tool.

There is a lack of data on ability and willingness of men who have sex with men (MSM) to self-fund HIV pre-exposure prophylaxis (PrEP). We aimed to explore how many eligible (PROUD study criteria) men may want PrEP and how many lower-risk MSM would be willing and able to self-fund this intervention. A self-completed anonymous questionnaire was distributed to MSM populations attending services. Of 377 participants, 81.5% were aware of PrEP. Fifty-three (15.5 %) were eligible, of whom 43 (81%) were very/extremely likely to want it. Of those ineligible, 229 (80%) were aware of PrEP and 106 (37.3%) were very/extremely likely to want it. Of eligible respondents 23% would be willing and able to pay at least £50 a month for PrEP. Of ineligible respondents this proportion was 21%. Our survey revealed high levels of awareness, understanding and willingness to take PrEP among MSM at high and lower risk of HIV acquisition. It indicated that over 70% of high-risk men would be unwilling or unable to self-fund PrEP, should it not be available on the NHS. For lower-risk MSM we estimated that capacity requirements for monitoring self-funded PrEP will be 50% higher than numbers eligible for PrEP. These factors will need to be taken into account when planning services.

HIV pre-exposure prophylaxis (PrEP) was FDA approved in 2012, but uptake remains low. To characterize what would facilitate health care providers' increased PrEP prescribing, we conducted a 10-city, online survey of 525 primary care providers (PCPs) and HIV providers (HIVPs) to assess awareness, knowledge, and experience with prescribing PrEP; and, comfort with and barriers to PrEP-related activities. Fewer PCPs than HIVPs had heard of PrEP (76 vs 98%), felt familiar with prescribing PrEP (28 vs. 76%), or had prescribed it (17 vs. 64%). PCPs were less comfortable than HIVPs with PrEP-related activities such as discussing sexual activities (75 vs. 94%), testing for acute HIV (83 vs. 98%), or delivering a new HIV diagnosis (80 vs. 95%). PCPs most frequently identified limited knowledge about PrEP and concerns about insurance coverage as prescribing barriers. PCPs and HIVPs differ in needs that will facilitate their PrEP prescribing. Efforts to increase PrEP uptake will require interventions to increase the knowledge, comfort, and skills of providers to prescribe PrEP.

The pharmacokinetics (PK) of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP), the active anabolites of tenofovir disoproxil fumarate (TDF), and emtricitabine (FTC) in blood, genital, and rectal compartments was determined in HIV-positive and seronegative adults who undertook a 60-day intensive PK study of daily TDF/FTC (plus efavirenz in HIV positives). Lymphocyte cell sorting, genital, and rectal sampling occurred once per subject, at staggered visits. Among 19 HIV-positive (3 female) and 21 seronegative (10 female) adults, TFV-DP in peripheral blood mononuclear cells (PBMC) accumulated 8.6-fold [95% confidence interval (CI): 7.2-10] from first-dose to steady-state concentration (Css) versus 1.7-fold (95% CI: 1.5-1.9) for FTC-TP. Css was reached in ∼11 and 3 days, respectively. Css values were similar between HIV-negative and HIV-positive individuals. Css TFV-DP in rectal mononuclear cells (1,450 fmol/10 6 cells, 898-2,340) was achieved in 5 days and was >10 times higher than PBMC (95 fmol/10 6 cells, 85-106), seminal cells (22 fmol/10 6 cells, 6-79), and cervical cells (111 fmol/10 6 cells, 64-194). FTC-TP Css was highest in PBMC (5.7 pmol/10 6 cells, 5.2-6.1) and cervical cells (7 pmol/10 6 cells, 2-19) versus rectal (0.8 pmol/10 6 cells, 0.6-1.1) and seminal cells (0.3 pmol/10 6 cells, 0.2-0.5). Genital drug concentrations on days 1-7 overlapped with estimated Css, but accumulation characteristics were based on limited data. TFV-DP and FTC-TP in cell sorted samples were highest and achieved most rapidly in CD14 + compared with CD4 + , CD8 + , and CD19 + cells. Together, these findings demonstrate cell-type and tissue-dependent cellular pharmacology, preferential accumulation of TFV-DP in rectal mononuclear cells, and rapid distribution into rectal and genital compartments., Competing Interests: Author Disclosure Statement Peter Anderson receives contract work and grant support from Gilead Sciences, paid to his institution. All other authors report no competing financial interests exit.

The new generation humanized mice (hu-mice) that permit continuous de novo generation of human hematopoietic cells have led to novel strategies in studying HIV-1 pathogenesis, prevention and therapies. HIV-1 infection of hu-mice results in chronic viremia and CD4+ T cell loss, thus mimicking key aspects of the disease progression. In addition, the new generation hu-mice are permissive for HIV-1 sexual transmission by vaginal and rectal routes thus allowing in vivo efficacy testing of new anti-HIV-1 drugs for prevention. Two leading models are currently being used, namely the hu-HSC mice and the BLT mice. Here we describe the methodology for generating both hu-HSC and BLT mice and their use in the study of HIV-1 transmission and prevention of infection by topical and oral administration of anti-retroviral drugs. Practical aspects of the methodologies are emphasized.

Objectives: This study evaluated the relationship between intracellular tenofovir diphosphate concentrations in peripheral blood mononuclear cells and prophylactic efficacy in a macaque model for HIV pre-exposure prophylaxis (PrEP)., Methods: Macaques were challenged with simian HIV (SHIV) via rectal inoculation once weekly for up to 14 weeks. A control group (n=34) received no drug, a second group (n=6) received oral tenofovir disoproxil fumarate/emtricitabine 3 days before each virus challenge and a third group (n=6) received the same dosing plus another dose 2 h after virus challenge. PBMCs were collected just before each weekly virus challenge. The relationship between tenofovir diphosphate in PBMCs and prophylactic efficacy was assessed with a Cox proportional hazards model., Results: The percentages of animals infected in the control, one-dose and two-dose groups were 97, 83 and 17, respectively. The mean (SD) steady-state tenofovir diphosphate concentration (fmol/10(6) cells) was 15.8 (7.6) in the one-dose group and 30.7 (10.1) in the two-dose group. Each 5 fmol tenofovir diphosphate/10(6) cells was associated with a 40% (95% CI 17%-56%) reduction in risk of SHIV acquisition, P=0.002. The tenofovir diphosphate concentration associated with a 90% reduction in risk (EC90) was 22.6 fmol/10(6) cells (95% CI 13.8-60.8)., Conclusions: The prophylactic EC90 for tenofovir diphosphate identified in macaques exposed rectally compares well with the EC90 previously identified in men who have sex with men (MSM; 16 fmol/10(6) cells, 95% CI 3-28). These results highlight the relevance of this model to inform human PrEP studies of oral tenofovir disoproxil fumarate/emtricitabine for MSM., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Cisgender women and transgender men are less likely to be assessed for PrEP eligibility, prescribed PrEP, or retained in PrEP care. Thus, this pilot PrEP educational intervention was tailored for healthcare providers (HCPs) in obstetrics/gynecology who provide care to cisgender women and transgender men in an academically-affiliated, public hospital women's health clinic. The three-lecture educational curriculum designed for HCPs focused on PrEP eligibility and counseling, formulations and adherence, and prescription and payment assistance programs. Pre- and post-intervention surveys assessed HCP knowledge and barriers to PrEP counseling and prescription. Among n = 49 participants (mean age = 32.8 years; 85.7% cisgender women, mean years practicing = 4.2 years) pre-intervention, 8.7% had prior PrEP training and 61.2% felt very/somewhat uncomfortable prescribing PrEP. Post-intervention, knowledge of PrEP contraindications, eligibility, follow-up care, and assistance programs all increased. HCPs identified key barriers to PrEP care including lack of a dedicated PrEP navigator, culturally and linguistically appropriate patient materials on PrEP resources/costs, and PrEP-related content integrated into EHRs. Ongoing PrEP educational sessions can provide opportunities to practice PrEP counseling, including information on financial assistance. At the institutional level, incorporating PrEP screening in routine clinical practice via EMR prompts, facilitating PrEP medication monitoring, and enhancing telehealth for follow-up care could enhance PrEP prescription. [ABSTRACT FROM AUTHOR]