Impact of Primary Letermovir Prophylaxis Versus Preemptive Antiviral Therapy for Cytomegalovirus on Economic and Clinical Outcomes after Hematopoietic Cell Transplantation.

Preemptive therapy (PET) historically has been the primary strategy to reduce early-onset cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplantation (HCT) but is associated with antiviral-associated toxicities and increases in healthcare resource utilization and cost. Despite its high cost, letermovir (LTV) prophylaxis has largely supplanted PET due to its effectiveness and tolerability. Direct comparisons between LTV and PET approaches on economic and clinical outcomes after allogeneic HCT remain limited. Objective: To compare total cost of care (inpatient and outpatient) between LTV prophylaxis and PET through day+180 after allogeneic HCT. Adult allogeneic CMV seropositive (R+) HCT recipients who initiated LTV <30 days after HCT between 01/01/18 and 12/31/18 were matched 1:1 to allogeneic CMV R+ HCT recipients between 01/01/15 and 12/31/17 (PET cohort). Patients were grouped into high-risk (HR) or standard-risk (SR) for CMV to compare the LTV and PET cohorts. Direct costs for each patient's index HCT admission and all subsequent inpatient and outpatient care through day+180 after HCT were determined and converted into 2021 US dollars and then to Medicare proportional dollars (MPD). A secondary analysis using 2019 average wholesale price was conducted to specifically evaluate anti-CMV medication costs. There were a total of 176 patients with 54 HR CMV pairs and 34 SR CMV pairs. No differences in survival between LTV and PET for both HR and SR CMV groups were observed. The rate of clinically significant CMV infection decreased for both HR CMV (11/54, 20.4% versus 38/54, 70.4%, P < .001) and SR CMV (1/34, 2.9% versus 12/34, 35.3%, P < .001) patients who were given LTV prophylaxis with corresponding reductions in val(ganciclovir) and foscarnet (HR CMV only) use. Among HR CMV patients, LTV prophylaxis was associated with reductions in CMV-related readmissions (3/54, 5.6% versus 18/54, 33.3%, P < .001) and outpatient visits within the first 100 days after HCT (20 versus 25, P = .002), and a decreased median total cost of care ($36,018 versus $75,525, P < .001) in MPD was observed. For SR CMV patients on LTV, a significant reduction in the median inpatient cost ($15,668 versus $27,818, P < .001) was found, but this finding was offset by a higher median outpatient cost ($26,145 versus $20,307, P = .030) that was not CMV-driven. LTV prophylaxis is highly effective in reducing clinically significant CMV reactivations for both HR and SR HCT recipients. In this study, LTV prophylaxis was associated with a decreased total cost of care for HR CMV patients through day+180. Specifically, reductions in CMV-related readmissions, exposure to CMV-directed antiviral agents, and outpatient visits in the first 100 days after HCT were observed. SR CMV patients receiving LTV prophylaxis benefited by having a reduced inpatient cost of care due to lowered room and pharmacy costs.

Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies - insights from the German NeuroTransData registry.

BACKGROUND: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have shown good efficacy in migraine prophylaxis. However, a subset of patients does not respond to the first mAb treatment and switches among the available mAbs. The goal of this study is to characterize the switching pattern of migraine patients treated with anti-CGRP(-receptor, -R) mAbs, and to describe the headache burden of those who did not switch, switched once, and switched twice. METHODS: This study used real world data from the NeuroTransData Cohort, a registry of migraine patients treated at outpatient neurology clinics across Germany. Patients who had received at least one anti-CGRP(-R) mAb were included. Headache diaries were collected at baseline and during treatment, along with quality of life measures every three months. Results were summarized for the subgroups of patients who did not switch and those with one and two switches. RESULTS: Of the 655 eligible patients, 479 did not switch, 135 switched once, 35 twice, and 6 three or more times. The ≥ 50% response rates for monthly migraine days were 64.7%, 50.7%, and 25.0% for the no switch, one switch, and two switches groups in their last treatment cycles, respectively. Quality of life measures improved for the no switch and one switch groups, but not for the two switches group. CONCLUSION: Patients who switched among anti-CGRP(-R) mAbs during the course of their treatment still benefited overall but to a lesser extent than those who did not switch. Treatment response in patients who switched twice was markedly lower compared to the no switch and one switch subgroup.

The efficacy and safety of hydroxychloroquine for COVID-19 prophylaxis and clinical assessment: an updated meta-analysis of randomized trials.

Background: Coronavirus disease 2019 (COVID-19), a disease that affected tens of millions of people, upended the lives of countless individuals around the globe. The chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) were the most frequently cited as potential treatments and preventatives against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The primary aim of this investigation was to scrutinize the effectiveness and safety of HCQ for COVID-19 prevention and to present powerful evidence and reference for clinical practice. Methods: PubMed, Ovid and the Cochrane COVID-19 Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 31, 2022. Randomized controlled trials (RCTs) trials that included participants who were SARS-CoV-2 negative at the time of registration were enrolled in this meta-analysis. The intervention group took HCQ or CQ orally. The control group was not blinded by quinine or placebo. Pooled relative risk (RR) of SARS-CoV-2 infection, mortality, hospitalization, adverse events, and compliance were calculated. The software tools utilized for statistical analyses were Stata 14 and Review Manager 5.3. Results: A total of 9 studies including 7,825 participants were enrolled. Bias of individual studies were assessed as low risk. The pooled RR for SARS-CoV-2 infection was 0.75 [95% confidence interval (CI): 0.68-0.83] (z=-4.01, P<0.0001; I2=11%). The pooled RR for hospitalization was 0.72 (95% CI: 0.35-1.50) (z=0.87, P=0.39; I2=0.0%). The pooled RR for mortality and adverse events were 3.26 (95% CI: 0.13-79.74) (z=0.72, P=0.47; I2=0.0%) and 1.90 (95% CI: 1.20-3.02) (z=2.73, P=0.0063; I2=94%). Conclusions: Results of this meta-analysis indicated significant impact of HCQ on SARS-CoV-2 infection with higher risk of adverse events. These findings must be considered with caution, and further research is necessary to delineate the specific circumstances where HCQ may be effective for COVID-19 prevention.

Utility of beta-lactam allergy assessment in patients receiving vancomycin for surgical prophylaxis.

Background: Beta-lactam antibiotics are first-line agents for most patients receiving antimicrobial prophylaxis in surgical procedures. Despite evidence showing low cross-reactivity between penicillins and cephalosporins, patients with beta-lactam allergies commonly receive vancomycin as an alternative to avoid allergic reaction. Methods: Adult patients receiving vancomycin for surgical prophylaxis with a reported beta-lactam allergy at our institution between August 2017 to July 2018 were retrospectively evaluated for potential eligibility for penicillin allergy testing and/or receipt of standard prophylaxis. Results: Among 830 patients who received vancomycin for surgical prophylaxis, 196 reported beta-lactam allergy and were included in the analysis. Approximately 40 % of surgeries were orthopedic. Of patients receiving vancomycin as first-line therapy, 189 (96.4 %) were potentially eligible for beta-lactam prophylaxis. Conclusions: Patients with beta-lactam allergies often qualify for receipt of a first-line antibiotic. An opportunity exists for improved allergy assessment as an antimicrobial stewardship intervention in surgical prophylaxis.

High Rates of Missed HIV Testing Among Oral PrEP Users in the United States From 2018-2021: A National Assessment on Compliance With HIV Testing Recommendations of the CDC PrEP Guidelines.

Background: The US Centers for Disease Control and Prevention recommends HIV testing every 3 months in oral PrEP users. We performed a national assessment of HIV testing compliance among oral PrEP users. Methods: We analyzed 408 910 PrEP prescriptions issued to 39 809 PrEP users using a national insurance claims database that contained commercial and Medicaid claims. We identified PrEP use based on pharmacy claims and outpatient diagnostic coding. We evaluated the percentage of PrEP prescription refills without HIV testing (identified by CPT codes) within the prior 3, 6, and 12 months using time to event methods. We performed subgroup and multivariate analyses by age, gender, race, insurance type, and geography. Results: Of 39 809 persons, 36 197 were commercially insured, 3612 were Medicaid-insured, and 96% identified as male; the median age (interquartile range) was 34 (29-44) years, and the Medicaid-insured PrEP users were 24% Black/African American, 44% White, and 9% Hispanic/Latinx. Within the prior 3, 6, and 12 months, respectively, the percentage of PrEP prescription fills in individuals without HIV Ag/Ab testing was 34.3% (95% CI, 34.2%-34.5%), 23.8% (95% CI, 23.7%-23.9%), and 16.6% (95% CI, 16.4%-16.7%), and the percentage without any type of HIV test was 25.8% (95% CI, 25.6%-25.9%), 14.6% (95% CI, 14.5%-14.7%), and 7.8% (95% CI, 7.7%-7.9%). Conclusions: Approximately 1 in 3 oral PrEP prescriptions were filled in persons who had not received an HIV Ag/Ab test within the prior 3 months, with evidence of health disparities. These findings inform clinical PrEP monitoring efforts and compliance with national HIV testing guidance to monitor PrEP users.

Life and Disability Insurance for People with or at Risk of HIV: Aligning Policy with Evidence.

Antiretroviral medications have substantially improved life expectancy for people with HIV. These medications are also highly effective in preventing HIV acquisition in people who do not have HIV, a strategy known as HIV preexposure prophylaxis (PrEP). Despite these advances, some life and disability insurers continue to deny or limit coverage for people with HIV, and some have even refused to cover people who are using PrEP to protect themselves. These policies unfairly deny people with HIV, PrEP users, and their families the peace of mind and financial protection that can come with life and disability insurance coverage. This article summarizes the current evidence on HIV treatment and prevention, arguing that underwriting decisions by life and disability insurers should not be made based on HIV status or use of PrEP.

Assessment of antimicrobial prescribing patterns, guidelines compliance, and appropriateness of antimicrobial prescribing in surgical-practice units: point prevalence survey in Malaysian teaching hospitals.

Objectives: This study sought to investigate the quality of antimicrobial prescribing among adult surgical inpatients besides exploring the determinants of non-compliance and inappropriate prescribing to inform stewardship activities. Methods: A cross-sectional point prevalence study employing Hospital National Antimicrobial Prescribing Survey (Hospital NAPS) was conducted in April 2019 at two teaching hospitals in Malaysia. Results: Among 566 surgical inpatients, 44.2% were receiving at least one antimicrobial, for a total of 339 prescriptions. Antimicrobials belonging to the World Health Organization's Watch group were observed in 57.8% of cases. Both hospitals exhibited similar types of antimicrobial treatments prescribed and administration routes. A significant difference in antimicrobial choice was observed between hospitals (p < 0.001). Hospital with electronic prescribing demonstrated better documentation practice (p < 0.001). Guidelines compliance, 32.8% (p = 0.952) and appropriateness, 55.2% (p = 0.561) did not significantly differ. The major contributors of inappropriateness were incorrect duration, (15%) and unnecessary broad-spectrum coverage, (15.6%). Non-compliance and inappropriate prescribing were found to be 2 to 4 times significantly higher with antimicrobial prophylaxis prescription compared to empirical therapy. Conclusion: Antimicrobial stewardship efforts to improve appropriate surgical prescribing are essential. These initiatives should prioritize surgical prophylaxis prescribing, focusing on reducing unnecessarily prolonged use and broad-spectrum antimicrobials, raising awareness among prescribers and promoting proper documentation.

Rabies death in an adolescent tribal girl diagnosed postmortem, in Kerala - the precious life, preventable loss and equity concerns.

BACKGROUND: Rabies is a neglected tropical disease endemic in 150 countries, including India where it is present in all states and union territories except Andaman and Nicobar Islands Lakshadweep. Kerala reports high incidence of animal bites. This article discusses the preventable death of a 17-year-old tribal girl due to rabies in Kerala and the equity concerns it raises. METHODS: The case study was conducted using qualitative methods such as rapid key informant interviews, interactions in tribal assembly meetings, unstructured participant observations, and document verification. Thematic analysis was used, and the results are presented as an ethnographic summary with the use of quotes to substantiate the observations. RESULTS: The girl had gone to a town with her sister for a few days when she developed difficulty in eating, behavioral abnormalities, and injuries on her body. She subsequently died, and a post-mortem revealed Negri bodies in her brain, confirming rabies as the cause of death. The girl had been bitten by a puppy from the forest eight months prior, but she did not receive post-exposure prophylaxis. Multiple dogs are kept in each household in the settlement, and the community takes good care of them since they protect them from wild animals. However, awareness about the need for post-exposure prophylaxis is low, and access to it is difficult for this population. The social problems in the settlement affect their quality of life and their interactions with the outside world. CONCLUSIONS: To prevent such deaths, it is essential to increase awareness and ensure equitable access to life-saving vaccines and immunoglobulin in hard-to-reach tribal areas. The cost-effectiveness of pre-exposure prophylaxis for children in high-risk areas such as this tribal settlement should be evaluated and compared with the WHO-recommended strategies of mass canine vaccination and One Health.

Experiences of oral pre-exposure prophylaxis use among heterosexual men accessing sexual and reproductive health services in South Africa: a qualitative study.

INTRODUCTION: South African men face a substantial burden of HIV and are less likely to test for HIV and initiate antiretroviral therapy if tested positive and more likely to die from AIDS-related causes than women. In addition to condoms and circumcision, guidelines provide for the use of daily oral pre-exposure prophylaxis (PrEP) as an HIV prevention intervention for any men who recognize their need and request PrEP. However, heterosexual men have not been a focus of PrEP programmes, and since its introduction, there is limited literature on PrEP use among men in South Africa. This study explores the experiences, motivators and barriers to oral PrEP use among heterosexual men accessing primary healthcare services in South Africa. METHODS: This study forms part of a mixed-methods implementation science study aimed at generating evidence for oral PrEP introduction and conducted in primary healthcare clinics in South Africa since 2018. Men aged ≥15 years who initiated oral PrEP and enrolled in a parent cohort study were purposefully invited to participate in an in-depth interview (IDI). Between March 2020 and May 2022, 30 men participated in IDIs exploring their motivators for PrEP use, and experiences with accessing health services. Interviews were audio recorded, transcribed and analysed thematically. RESULTS: The final analysis included 28 heterosexual men (18-56 years old). Motivations to initiate PrEP included fear of acquiring HIV, self-perceived vulnerability to HIV and mistrust in relationships; health systems factors which motivated PrEP use included the influence of healthcare providers, educational materials and mobile services. Perceived reduction in HIV vulnerability and changing proximity to partners were reasons for PrEP discontinuation. Side effects, daily-pill burden and stigma were noted as challenges to PrEP use. Health system barriers to PrEP use included limited PrEP availability, school and work demands, and inconsistent mobile clinic schedules. CONCLUSIONS: Our study reports on the experiences of heterosexual men accessing oral PrEP in real-world settings and contributes to the limited literature among this population. We highlight multiple levels which could be strengthened to improve men's PrEP use, including individual support, education among partners and communities, and addressing health system barriers to access.

Gynecological Cancer and Venous Thromboembolism: A Narrative Review to Increase Awareness and Improve Risk Assessment and Prevention.

The prevention and appropriate management of venous thromboembolism in cancer patients is of paramount importance. However, the literature data report an underestimation of this major problem in patients with gynecological cancers, with an inconsistent venous thromboembolism risk assessment and prophylaxis in this patient setting. This narrative review provides a comprehensive overview of the available evidence regarding the management of venous thromboembolism in cancer patients, focusing on the specific context of gynecological tumors, exploring the literature discussing risk factors, risk assessment, and pharmacological prophylaxis. We found that the current understanding and management of venous thromboembolism in gynecological malignancy is largely based on studies on solid cancers in general. Hence, further, larger, and well-designed research in this area is needed.

In the fight against HIV/AIDS: the arduous implementation of government-funded pre-exposure prophylaxis programme in Taiwan.

INTRODUCTION: The government-funded pre-exposure prophylaxis (PrEP) programme was targeted to those aged under 30 years or serodiscordant couples and implemented in September 2018-October 2020 in Taiwan. The study aimed to examine the effectiveness of the programme and the relationship between sexually transmitted disease (STD) and HIV seroconversion. METHODS: This study was a retrospective cohort analysis with questionnaires designed for participants who joined the aforementioned programme in the PrEP-designated hospitals. The questionnaires included sociodemographic factors, sexual risk behaviours, number and types of sexual partners, and usage of narcotics filled in at the beginning of the programme and every 3 months. The McNemar test was used for the paired questionnaire analysis. The HIV seroconversion status among STD-notified patients nationwide was confirmed by using the data linkage method, followed up until October 2021 with stratification of PrEP programme participation or not. RESULTS: The programme recruited 2155 people. 11 participants (0.5%) had seroconversion within the programme, while 26 (1.2%) had seroconversion after withdrawing from the programme. Overall, 1892 subjects with repeated questionnaires were included in the analysis for behaviour changes with median follow-up of 289 days. After joining the programme, 94.7% of them claimed that they had sexual behaviours: the rate of those who had condomless sex rose to 5.5% (p<0.001) and the rate of those who used narcotics decreased to 2% (p<0.001), compared with their response in the pre-questionnaire. Notably, the frequency of non-use of narcotics in recent 3 months increased from 16.9% to 38.4% in the pre-questionnaire and post-questionnaire responses, among the 177 who had claimed narcotics usage in recent 12 months (p=0.003). More HIV seroconversion was found among patients with STD who did not join the programme than those who joined the programme (8.7% vs 4.9%, p=0.031). CONCLUSIONS: The government-funded programme showed HIV case reduction and positive changes in health behaviours except for condomless sex which had increased prevalence. The reduction of HIV cases was also observed among people with STD. More resources should be allocated to the PrEP programme.

A quality improvement intervention on surgical prophylaxis impact in antibiotic consumption and cost in selected surgical procedures.

BACKGROUND: Improper compliance with antibiotic prophylaxis (AP) in surgery is associated with an increased risk of surgical site infection (SSI), and impacts the efficiency of healthcare. OBJECTIVE: Evaluate the impact of an intervention in compliance with AP in selected surgical procedures and its effect on antibiotic consumption and cost. METHODS: A prospective interventional study was performed in a community hospital from January to December 2022. The baseline period was considered January-April 2022 and the intervention period May-December 2022. All patients who underwent cesarean section, appendectomies, hernia surgery, open reduction and internal fixation (ORIF), abdominoplasty, and cholecystectomy during the study period were selected. The intervention includes staff education, pharmacy interventions, monitoring the quality of prescriptions and feedback, and improved role of anesthesia staff, and department champions. RESULTS: The study involved 192 and 617 surgical procedures in the baseline and intervention periods respectively. The compliance with timing, selection, dose, and discontinuation achieved 100%, 99.2%, and 97.6% from baseline figures of 92.7%, 95.8%, and 81.3%, respectively. The antibiotic consumption was reduced by 55.1% during the intervention with a higher contribution of other antibiotics (94.1% reduction) in comparison with antibiotics as per policy (31.2% reduction). The cost was reduced by 47.2% (antibiotic as per policy 31.9%, other antibiotics 94.2%). CONCLUSION: The implemented strategy was effective in improving the quality of antibiotic prophylaxis with a significant impact in reducing antibiotic consumption and cost.

Avoiding Shots in the Dark: Learning from the Past To Inform the Implementation of Long-Acting Injectable Pre-Exposure Prophylaxis for Black American Cisgender Women.

The FDA's approval of long-acting injectable cabotegravir pre-exposure prophylaxis (LAI PrEP) as an alternative to daily oral PrEP represents a crucial development in HIV prevention, particularly for American Black cisgender women who face high HIV-1 risks. Yet, uptake may be hindered by racial and gender inequities. Addressing these requires learning from the roll-out of oral PrEP, creating culturally tailored PrEP campaigns, and enhancing provider training to meet Black women's needs. Tools for discussing PrEP within personal relationships and product preference research tailored to Black women's needs are essential for effective LAI PrEP delivery. Deliberative implementation of LAI PrEP must employ strategies that are community-sensitive, -responsive, and -inclusive. It should prioritize the incorporation of Black women's voices in decision-making and should promote community-led strategies. By addressing historical injustices and fostering trust, healthcare systems can enhance LAI PrEP uptake by Black women. Emphasizing a community-centered approach that ensures health equity and acknowledges the crucial role that social media and Black-led organizations play in promoting PrEP awareness and adoption within Black communities is necessary for successful implementation.

Assessment of the appropriateness of stress ulcer prophylaxis use and its determinants among admitted surgical patients at Debre Berhan University Hakim Gizaw Hospital, Ethiopia. A hospital-based cross-sectional study.

Introduction: Pharmacological stress ulcer prophylaxis (SUP) has been recommended for many years to reduce the risk of clinically significant upper gastrointestinal (GI) bleeding caused by stress ulcers (SUs). Stress-related ulcer bleeding in surgical patients significantly increases morbidity and mortality. Therefore, preventing stress-induced hemorrhage is the most appropriate measure for patients who are at increased risk. However, the inappropriate use of SUP has increased in recent years, and its use in Ethiopian surgical patients has not been well studied. Objective: The aim of this study was to assess the appropriateness of SUP use and its determinants among admitted surgical patients at Debre Berhan University Hakim Gizaw Hospital (DBUHGH), Ethiopia. Methods: We randomly selected 230 patients from the whole cross-sectional group of all surgical patients at DBUHGH from 1 February to 30 June 2023. The risk of stress ulcer (SU) development was assessed using the modified American Society of Health-System Pharmacists (ASHP) guidelines. For data analysis, we used SPSS version 25. Results: The mean age of study participants was 47.2 years (SD ± 20.4), and out of the total of 230, 130 (56.5%) were women. Approximately 66% of study participants took inappropriate SUP based on ASHP guidelines criteria. The most commonly used drug class for SUP was histamine-2 receptor blockers 115 (50%). Study participants who have a Charlson Comorbidity Index Score of moderate and GI bleeding have been significantly associated with the inappropriate use of SUP. Conclusion: In our study, inappropriate SUP use was common in the surgical ward of DBUHGH. This may be an area that requires further and more focused working together among clinical pharmacists and medical professionals in an institution-specific SUP protocol that aids clinicians in identifying appropriate candidates for SUP medication.

Nirsevimab: Expansion of Respiratory Syncytial Virus Prevention Options in Neonates, Infants, and At-Risk Young Children.

OBJECTIVE: Review available data from clinical trials of nirsevimab for efficacy and safety in the setting of respiratory syncytial virus (RSV) prophylaxis in infants and children, while exploring nirsevimab's role in clinical practice and highlighting continuing questions. DATA SOURCES: A literature search of PubMed was conducted utilizing the phrases "nirsevimab" and "medi8897." Additional references were identified through found references. Organizational guidelines, medication labeling, and regulatory organization presentations were utilized. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials investigating nirsevimab in infants and children were included as well as other references on pharmacology, pharmacokinetics, and pharmacoeconomics. DATA SYNTHESIS: Nirsevimab, a once-a-season monoclonal antibody, demonstrated a 79.5% (95% CI, 65.9-87.7; P < 0.00001) lower incidence of RSV-associated medically attended lower respiratory tract infections (MA RSV-associated LRTI) and 77.3% (95% CI, 50.3-89.7; P = 0.0002) reduction in hospitalizations for RSV-associated MA-LRTI across 2 placebo-controlled studies. Nirsevimab demonstrated comparable safety to placebo with minor dermatologic reactions being the most common adverse event (0.9% vs 0.6%). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING AGENTS: Nirsevimab was approved by the US Food and Drug Administration, and recommended by the Advisory Committee on Immunization Practices and American Academy of Pediatrics for broad administration to infants entering their first RSV season and at risk patients during their second RSV season. Questions remain over efficacy in infants born < 29-week gestation and other economical considerations. CONCLUSIONS: Nirsevimab demonstrated clinical efficacy in reducing RSV-associated MA-LRTI and RSV-associated hospitalizations in infants and was well tolerated.

An HIV-1 risk assessment tool for women aged 15-49 in African countries: A pooled analysis across 15 nationally representative surveys.

BACKGROUND: Women in Africa disproportionately acquire HIV-1. Understanding which women are most likely to acquire HIV-1 can guide focused prevention with pre-exposure prophylaxis (PrEP). Our objective is to identify women at highest risk of HIV-1 and estimate PrEP efficiency at different sensitivity levels. METHODS: Nationally representative data were collected from 2015-2019 from 15 population-based household surveys. This analysis included women aged 15-49 who tested HIV-1 sero-negative or had recent HIV-1. Least absolute shrinkage and selection operator regression models were fit with 28 variables to predict recent HIV-1. Models were trained on the full population and internally cross-validated. Performance was evaluated using area under the receiver-operating-characteristic curve (AUC), sensitivity, and number needed to treat (NNT) with PrEP to avert one infection. RESULTS: Among 209,012 participants 248 had recent HIV-1 infection, representing 118 million women and 402,000 (95% CI: 309,000-495,000) new annual infections. Two variables were retained in the model: living in a subnational area with high HIV-1 viremia and having a sexual partner living outside the home. Full-population AUC was 0.80 (95% CI: 0.76-0.84); cross-validated AUC was 0.79 (95% CI: 0.75-0.84). At a sensitivity of 33%, up to 130,000 cases could be averted if 7.9 million women were perfectly adherent to PrEP; NNT would be 61. At a sensitivity of 67%, up to 260,000 cases could be averted if 25.1 million women were perfectly adherent to PrEP; the NNT would be 96. CONCLUSIONS: This risk assessment tool was generalizable, predictive, and parsimonious with tradeoffs between reach and efficiency.

Adapting mHealth Interventions (PrEPmate and DOT Diary) to Support PrEP Retention in Care and Adherence Among English and Spanish-Speaking Men Who Have Sex With Men and Transgender Women in the United States: Formative Work and Pilot Randomized Trial.

BACKGROUND: A growing number of mobile health (mHealth) technologies are being developed to support HIV preexposure prophylaxis (PrEP) adherence and persistence; however, most tools have focused on men who have sex with men (MSM), and few are available in Spanish. To maximize the potential impact of these tools in reducing gender and racial/ethnic disparities and promoting health equity, mHealth tools tailored to Spanish-speaking people and transgender women are critically needed. OBJECTIVE: The aim of this study is to adapt and tailor 2 mHealth technologies, PrEPmate and DOT Diary, to support daily PrEP adherence and persistence among Spanish-speaking MSM and English- and Spanish-speaking transgender women and to evaluate the feasibility and acceptability of these tools. METHODS: PrEPmate, an interactive, bidirectional, text messaging intervention that promotes personalized communication between PrEP users and providers, and DOT Diary, a mobile app that promotes self-management of PrEP use and sexual health through an integrated electronic pill-taking and sexual activity diary, were previously developed for English-speaking MSM. We conducted 3 focus groups with 15 English- and Spanish-speaking transgender women and MSM in San Francisco and Miami to culturally tailor these tools for these priority populations. We then conducted a 1-month technical pilot among 21 participants to assess the usability and acceptability of the adapted interventions and optimize the functionality of these tools. RESULTS: Participants in focus groups liked the "human touch" of text messages in PrEPmate and thought it would be helpful for scheduling appointments and asking questions. They liked the daily reminder messages, especially the fun facts, gender affirmations, and transgender history topics. Participants recommended changes to tailor the language and messages for Spanish-speaking and transgender populations. For DOT Diary, participants liked the adherence tracking and protection level feedback and thought the calendar functions were easy to use. Based on participant recommendations, we tailored language within the app for Spanish-speaking MSM and transgender women, simplified the sexual diary, and added motivational badges. In the technical pilot of the refined tools, mean System Usability Scale scores were 81.2/100 for PrEPmate and 76.4/100 for DOT Diary (P=.48), falling in the "good" to "excellent" range, and mean Client Satisfaction Questionnaire scores were 28.6 and 28.3 for PrEPmate and DOT Diary, respectively (maximum possible score=32). Use of both tools was high over the 1-month pilot (average of 10.5 messages received from each participant for PrEPmate; average of 17.6 times accessing the DOT Diary app), indicating good feasibility for both tools. CONCLUSIONS: Using a user-centered design approach, we culturally tailored PrEPmate and DOT Diary to support daily PrEP use among Spanish-speaking MSM and English- and Spanish-speaking transgender women. Our positive findings in a technical pilot support further testing of these mHealth interventions in an upcoming comparative effectiveness trial.

Addressing Unmet PrEP Needs in Women: Impact of a Laboratory-Driven Protocol at an Urban, Essential Hospital.

Background: HIV pre-exposure prophylaxis (PrEP) uptake in women remains low. We developed a laboratory result-driven protocol to link women with a positive bacterial sexually transmitted infection (STI) to HIV PrEP at an urban safety-net hospital. Methods: Electronic health records of women with positive chlamydia, gonorrhea, and/or syphilis tests were reviewed, and those eligible for PrEP were referred for direct or primary care provider-driven outreach. We assessed the proportion of women with STIs who received PrEP offers, acceptance, and prescriptions before (July 1, 2018-December 31, 2018) and after (January 1, 2019-June 30, 2020) implementation to evaluate changes in the delivery of key elements of the PrEP care cascade (ie, PrEP offers, acceptance, and prescribing) for women with STIs after protocol implementation. Results: The proportion of women who received PrEP offers increased from 7.6% to 17.6% (P < .001). After multivariable adjustment, only the postintervention period was associated with PrEP offers (odds ratio [OR], 2.49; 95% CI, 1.68-3.68). In subgroup analyses, PrEP offers increased significantly among non-Hispanic Black (OR, 2.75; 95% CI, 1.65-4.58) and Hispanic (OR, 5.34; 95% CI, 1.77-16.11) women but not among non-Hispanic White women (OR, 1.49; 95% CI, 0.54-4.05). Significant changes in PrEP acceptance and prescriptions were not observed in the sample overall. Conclusions: A laboratory result-driven protocol was associated with a significant increase in PrEP offers to Black and Hispanic women with STI. These results provide concrete suggestions for health systems seeking to increase PrEP access and equity among women.

Estimating the costs and perceived benefits of oral pre-exposure prophylaxis (PrEP) delivery in ten counties of Kenya: a costing and a contingent valuation study.

Background: Kenya included oral PrEP in the national guidelines as part of combination HIV prevention, and subsequently began providing PrEP to individuals who are at elevated risk of HIV infection in 2017. However, as scale-up continued, there was a recognized gap in knowledge on the cost of delivering oral PrEP. This gap limited the ability of the Government of Kenya to budget for its PrEP scale-up and to evaluate PrEP relative to other HIV prevention strategies. The following study calculated the actual costs of oral PrEP scale-up as it was being delivered in ten counties in Kenya. This costing also allowed for a comparison of various models of service delivery in different geographic regions from the perspective of service providers in Kenya. In addition, the analysis was also conducted to understand factors that indicate why some individuals place a greater value on PrEP than others, using a contingent valuation technique. Methods: Data collection was completed between November 2017 and September 2018. Costing data was collected from 44 Kenyan health facilities, consisting of 23 public facilities, 5 private facilities and 16 drop-in centers (DICEs) through a cross-sectional survey in ten counties. Financial and programmatic data were collected from financial and asset records and through interviewer administered questionnaires. The costs associated with PrEP provision were calculated using an ingredients-based costing approach which involved identification and costing of all the economic inputs (both direct and indirect) used in PrEP service delivery. In addition, a contingent valuation study was conducted at the same 44 facilities to understand factors that reveal why some individuals place a greater value on PrEP than others. Interviews were conducted with 2,258 individuals (1,940 current PrEP clients and 318 non-PrEP clients). A contingent valuation method using a "payment card approach" was used to determine the maximum willingness to pay (WTP) of respondents regarding obtaining access to oral PrEP services. Results: The weighted cost of providing PrEP was $253 per person year, ranging from $217 at health centers to $283 at dispensaries. Drop-in centers (DICEs), which served about two-thirds of the client volume at surveyed facilities, had a unit cost of $276. The unit cost was highest for facilities targeting MSM ($355), while it was lowest for those targeting FSW ($248). The unit cost for facilities targeting AGYW was $323 per person year. The largest percentage of costs were attributable to personnel (58.5%), followed by the cost of drugs, which represented 25% of all costs. The median WTP for PrEP was $2 per month (mean was $4.07 per month). This covers only one-third of the monthly cost of the medication (approximately $6 per month) and less than 10% of the full cost of delivering PrEP ($21 per month). A sizable proportion of current clients (27%) were unwilling to pay anything for PrEP. Certain populations put a higher value on PrEP services, including: FSW and MSM, Muslims, individuals with higher education, persons between the ages of 20 and 35, and households with a higher income and expenditures. Discussion: This is the most recent and comprehensive study on the cost of PrEP delivery in Kenya. These results will be used in determining resource requirements and for resource mobilization to facilitate sustainable PrEP scale-up in Kenya and beyond. This contingent valuation study does have important implications for Kenya's PrEP program. First, it indicates that some populations are more motivated to adopt oral PrEP, as indicated by their higher WTP for the service. MSM and FSW, for example, placed a higher value on PrEP than AGYW. Higher educated individuals, in turn, put a much higher value on PrEP than those with less education (which may also reflect the higher "ability to pay" among those with more education). This suggests that any attempt to increase demand or improve PrEP continuation should consider these differences in client populations. Cost recovery from existing PrEP clients would have potentially negative consequences for uptake and continuation.

Impact of national commissioning of pre-exposure prophylaxis (PrEP) on equity of access in England: a PrEP-to-need ratio investigation.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition. In England, NHS availability was limited to participants of the PrEP Impact Trial until late 2020. Some key populations at greater risk of HIV were under-represented in the trial suggesting inequities in trial PrEP access. We used the PrEP-to-need ratio (PnR; number of PrEP users divided by new HIV diagnoses) to investigate whether PrEP access improved following routine commissioning in October 2020 and identify populations most underserved by PrEP. METHODS: Aggregated numbers of people receiving ≥1 PrEP prescription and non-late new HIV diagnoses (epidemiological proxy for PrEP need) were taken from national surveillance data sets. We calculated the PnR across socio-demographics during Impact (October 2017 to February 2020; pre-COVID-19 pandemic) and post-commissioning PrEP era (2021) in England. RESULTS: PnR increased >11 fold, from 4.2 precommissioning to 48.9 in 2021, due to a fourfold reduction in non-late new HIV diagnoses and near threefold increase in PrEP users. PnR increased across genders, however, the men's PnR increased 12-fold (from 5.4 precommissioning to 63.9 postcommissioning) while the women's increased sevenfold (0.5 to 3.5). This increasing gender-based inequity was observed across age, ethnicity and region of residence: white men had the highest PnR, increasing >13 fold (7.1 to 96.0), while Black African women consistently had the lowest PnR, only increasing slightly (0.1 to 0.3) postcommissioning, suggesting they were the most underserved group. Precommissioning, the PnR was 78-fold higher among white men than Black women, increasing to 278-fold postcommissioning. CONCLUSIONS: Despite the overall increase in PrEP use, substantial PrEP Impact trial inequities widened postcommissioning in England, particularly across gender, ethnicity and region of residence. This study emphasises the need to guide HIV combination prevention based on equity metrics relative to the HIV epidemic. The PnR could support the optimisation of combination prevention to achieve zero new HIV infections in England by 2030.