Preexposure Prophylaxis to Prevent Acquisition of HIV: US Preventive Services Task Force Recommendation Statement.

Importance: An estimated 1.2 million persons in the US currently have HIV, and more than 760 000 persons have died of complications related to HIV since the first cases were reported in 1981. Although treatable, HIV is not curable and has significant health consequences. Therefore, effective strategies to prevent HIV are an important public health and clinical priority. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of preexposure prophylaxis with antiretroviral therapy for the prevention of HIV acquisition, and the diagnostic accuracy of risk assessment tools to identify persons at increased risk of HIV acquisition. Population: Adolescents and adults who do not have HIV and are at increased risk of HIV. Evidence Assessment: The USPSTF concludes with high certainty that there is a substantial net benefit from the use of effective antiretroviral therapy to reduce the risk of acquisition of HIV in persons at increased risk of acquiring HIV. Recommendation: The USPSTF recommends that clinicians prescribe preexposure prophylaxis using effective antiretroviral therapy to persons at increased risk of HIV acquisition to decrease the risk of acquiring HIV. (A recommendation).

Implementation of a national HIV pre-exposure prophylaxis service is associated with changes in characteristics of people with newly diagnosed HIV: a retrospective cohort study.

OBJECTIVES: To review characteristics of individuals newly diagnosed with HIV following implementation of a national pre-exposure prophylaxis (PrEP) programme (comprehensive PrEP services, delivered in sexual health clinics) to inform future delivery and broader HIV prevention strategies. METHODS: We extracted data from national HIV databases (July 2015-June 2018). We compared sociodemographic characteristics of individuals diagnosed in the period before and after PrEP implementation, and determined the proportion of 'potentially preventable' infections with the sexual health clinic-based PrEP delivery model used. RESULTS: Those diagnosed with HIV before PrEP implementation were more likely to be male (342/418, 81.8% vs 142/197, 72.1%, p=0.005), be white indigenous (327/418, 78.2% vs 126/197, 64.0%, p<0.001), report transmission route as sex between men (219/418, 52.4% vs 81/197, 41.1%, p=0.014), and have acquired HIV in the country of the programme (302/418, 72.2% vs 114/197, 57.9% p<0.001) and less likely to report transmission through heterosexual sex (114/418, 27.3% vs 77/197, 39.1%, p=0.002) than after implementation.Pre-implementation, 8.6% (36/418) diagnoses were 'potentially preventable' with the PrEP model used. Post-implementation, this was 6.6% (13/197), but higher among those with recently acquired HIV (49/170, 28.8%). Overall, individuals with 'potentially preventable' infections were more likely to be male (49/49, 100% vs 435/566, 76.9%, p<0.001), aged <40 years (37/49, 75.5% vs 307/566, 54.2%, p=0.004), report transmission route as sex between men (49/49, 100% vs 251/566, 44.3%, p<0.001), have previously received post-exposure prophylaxis (12/49, 24.5% vs 7/566, 1.2%, p<0.001) and less likely to be black African (0/49, 0% vs 67/566, 11.8%, p=0.010) than those not meeting this definition. CONCLUSIONS: The sexual health clinic-based national PrEP delivery model appeared to best suit men who have sex with men and white indigenous individuals but had limited reach into other key vulnerable groups. Enhanced models of delivery and HIV combination prevention are required to widen access to individuals not benefiting from PrEP at present.

Social Impact of Prophylactic Migraine Treatments in Germany: A State-Transition and Open Cohort Approach.

OBJECTIVES: Migraine is a highly prevalent neurological disorder. The most characteristic symptom of migraine is moderate to severe recurrent headache along with other neurological symptoms. In this study, we modeled the potential reduction in migraine days and corresponding avoided productivity losses if erenumab was prescribed to the patient population indicated for prophylactic migraine treatment (≥ 4 monthly migraine days [MMDs]) in Germany from 2020 to the end of 2027. METHODS: We simulated the incremental benefits of erenumab against the standard of care. Response rates, transition probabilities, discontinuation rates, and productivity estimates were derived from the erenumab clinical trial program. Patients had a probability of residing in 1 of 7 states, given the MMDs in addition to the probability of death. Based on accrued MMDs in every cycle, days of absenteeism and presenteeism for paid and unpaid work were derived. Paid work was monetized according to gross value added using the human capital approach, whereas unpaid work was valuated according to the proxy good method. In addition, downstream macroeconomic effects were captured using value-added multipliers. Direct medical costs were concomitantly calculated. RESULTS: Our results show that prescribing erenumab for the indicated population in Germany could lead to a reduction of 166 million migraine days annually and reduce productivity losses in the range of €27 billion. This includes €13.1 billion from direct productivity and €13.5 billion from economic value chain effects. CONCLUSIONS: This study highlights the macroeconomic effects of a systematic introduction of novel inhibitors of the calcitonin gene-related peptide pathway for migraine in Germany.

Drug dosing in the critically ill obese patient: a focus on medications for hemodynamic support and prophylaxis.

Medications used for supportive care or prophylaxis constitute a significant portion of drug utilization in the intensive care unit. Evidence-based guidelines are available for many aspects of supportive care but drug doses listed are typically for patients with normal body habitus and not morbid obesity. Failure to account for the pharmacokinetic changes that occur with obesity can lead to an incorrect dose and treatment failure or toxicity. This paper is intended to help clinicians design initial dosing regimens in critically ill obese patients for medications commonly used for hemodynamic support or prophylaxis. A detailed literature search of medications used for supportive care or prophylaxis listed in practice guidelines was conducted with an emphasis on obesity, pharmacokinetics and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided. For medications used for hemodynamic support, a similar strategy can be used as in non-obese patients. Similarly, medications for stress ulcer prophylaxis do not need to be adjusted. Anticoagulants for venous thromboembolism prophylaxis, on the other hand, require an individualized approach where higher doses are necessary.

US Guideline Criteria for Human Immunodeficiency Virus Preexposure Prophylaxis: Clinical Considerations and Caveats.

Clinical guidelines for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) developed by the US Centers for Disease Control and Prevention have been instrumental in the implementation of PrEP in medical practices throughout the country. However, the eligibility criteria contained within may inadvertently limit PrEP access for some patients. We describe the following key considerations and caveats related to these criteria: promotion of a selective vs universal approach to sexual health education involving PrEP; misalignment between criteria stated in the table and text boxes; problematic categorization and confounding of sexual orientation, gender identity, and risk behavior; underemphasis of network/community-level drivers of HIV transmission; oversimplification of serodiscordant risk; and lack of clarity surrounding the relevance of condoms to PrEP eligibility. We offer concrete recommendations to address the identified issues and strengthen future iterations of the guidelines, applying these recommendations in an alternative table of "criteria."

A Cross-sectional Survey of Internal Medicine Resident Knowledge, Attitudes, Behaviors, and Experiences Regarding Pre-Exposure Prophylaxis for HIV Infection.

BACKGROUND: Pre-exposure prophylaxis (PrEP) for HIV is effective, yet many providers continue to lack knowledge and comfort in providing this intervention. It remains unclear whether internal medicine (IM) residents receive appropriate training in PrEP care and if this affects their future practices. OBJECTIVE: We sought to evaluate the relationship between current IM residents' prior PrEP training and knowledge, comfort, and practice regarding the provision of PrEP. DESIGN AND PARTICIPANTS: We created an online survey to assess IM residents' knowledge, attitudes, and behaviors related to PrEP. The survey was distributed among five IM programs across the USA. KEY RESULTS: We had a 35% response rate. Of 229 respondents, 96% (n = 220) had heard of PrEP but only 25% (n = 51) had received prior training and 11% (n = 24) had prescribed PrEP. Compared with those without, those with prior training reported good to excellent knowledge scores regarding PrEP (80% versus 33%, p < 0.001), more frequent prescribing (28% versus 7%, p = 0.001), and higher comfort levels with evaluating risk for HIV, educating patients, and monitoring aspects of PrEP (75% versus 26%, 56% versus 16%, and 47% versus 8%, respectively; all p values < 0.0001). While only 25% (n = 51) had received prior training, 75% (n = 103) of respondents reported that training all providers at their continuity clinic sites would improve implementation. CONCLUSIONS: We found that prior training was associated with higher levels of self-reported PrEP knowledge, comfort, and prescribing behaviors. Given the significant need for PrEP, IM residents should be trained to achieve adequate knowledge and comfort levels to prescribe it. This study demonstrates that providing appropriate PrEP training for IM residents may lead to an increase in the pool of graduating IM residents prescribing PrEP.

A Mixed Methods Evaluation of an Inclusive Sexual History Taking and HIV Prevention Curriculum for Trainees.

BACKGROUND: Health disparities exist in HIV risk in the USA among the lesbian-gay-bisexual-transgender-queer (LGBTQ) community. There is also scarce literature on curricula for HIV prevention and pre-exposure prophylaxis (PrEP) for trainees. AIM: To create a curriculum to train residents to perform inclusive sexual history taking and HIV prevention care. The curriculum covers sexual history, LGBTQ health, sexually transmitted infections, and HIV risk assessment and risk reduction counseling including use of PrEP. SETTING: A dedicated PrEP Clinic was created within an Academic Medical Center Outpatient HIV Clinic. Patients were primarily LGBTQ identified, but also included HIV sero-discordant couples, cisgender individuals, heterosexual invididuals, and those with experience of homelessness, sex work, and substance abuse. PARTICIPANTS: Thirty-four internal medicine residents completed the course between November 2017 and May 2018. PROGRAM DESCRIPTION: The curriculum was delivered as Just in Time Teaching (JiTT) via online virtual patient cases followed by directly observed clinical care at a large urban PrEP clinic. PROGRAM EVALUATION AND RESULTS: The effectiveness of the curriculum was assessed through paired pre/post-self-assessment surveys (n = 19), additional post-surveys on the online modules (n = 22), and interviews (n = 9). Many respondents reported no prior training or inadequate prior training in the course content. As a result of the course, participants reported statistically significant increased confidence and comfort in all seven HIV prevention topic areas, with the greatest gains in safe sex counseling for LGBTQ patients and in discussing PrEP (mean changes of 1.21, 1.58 on 5-point Likert scale, respectively, p < 0.0001). Six of nine interviewees post-course had applied what they learned to patient care; five indicated their learning would benefit patients. DISCUSSION: An HIV prevention curriculum focused on cultural humility in care can improve trainee's skills in HIV risk reduction counseling, including PrEP, among all patients including those identifying as LGBTQ.

Are current guidelines adapted for patient eligibility to PrEP? A case report.

BACKGROUND: Despite effective antiretroviral therapy developed over the last decade, HIV infection remains a major worldwide public health problem. Recently, a promising preventive treatment has been made available for HIV prophylaxis, PrEP for pre-ExPosure Prophylaxis. Indeed, it was shown to significantly reduce the risk of HIV infection in patients exposed to high risk of infection such as men having sex with men (MSM), heterosexuals and people who inject drugs. Several issues pertaining to PrEP remain uncertain including short and long-term adverse events, drug resistance, risk compensation and resurgence of other sexually transmitted infections. CASE PRESENTATION: We report a case of a 52-year-old MSM eligible for PrEP as he was exposed to a high risk of HIV infection, presented no clinical symptoms of HIV primary infection and was seronegative for HIV. PrEP therapy was then initiated with fixed association of emtricitabine-tenofovir disoproxil. One month later, HIV tests using two different assays were positive, despite perfect compliance reported by the patient and confirmed by plasma drug level. A retrospective search for plasma viral RNA in the blood sample before PrEP initiation turned out positive. Genotyping and treatment sensitivity performed on sample after one month of PrEP showed a virus resistance to lamivudine and emtricitabine. Similar cases in the literature and pivotal studies have reported HIV infections in patients initiating or undergoing PrEP. These patients where either infected but still seronegative, displaying no clinical symptoms upon enrollment, or became infected during PrEP. Reasons are mainly poor compliance to treatment, resistance to PrEP, and lack of diagnosis before PrEP. Guidelines advocate safe sex behavior before initiation, search for clinical signs of HIV primary infection and two different serologic tests performed with one-month interval. DISCUSSION AND CONCLUSIONS: Our patient newly HIV infected received PrEP as he was still seronegative. Current recommendations fail to screen recently HIV infected, but still seronegative patients who are initiating PrEP. This issue raises strong concerns regarding the lack of adequate selection for eligibility to PrEP and may contribute to exposing partners to HIV infection and select viral mutations. Infection risk could be minimized by search for plasma viral HIV RNA at pre-inclusion, at least for patients suspected of unsafe behaviors such as non-respect of the non-exposure period before PrEP initiation.

The Society for Obstetric Anesthesia and Perinatology Consensus Statement on the Anesthetic Management of Pregnant and Postpartum Women Receiving Thromboprophylaxis or Higher Dose Anticoagulants.

Venous thromboembolism is recognized as a leading cause of maternal death in the United States. Thromboprophylaxis has been highlighted as a key preventive measure to reduce venous thromboembolism-related maternal deaths. However, the expanded use of thromboprophylaxis in obstetrics will have a major impact on the use and timing of neuraxial analgesia and anesthesia for women undergoing vaginal or cesarean delivery and other obstetric surgeries. Experts from the Society of Obstetric Anesthesia and Perinatology, the American Society of Regional Anesthesia, and hematology have collaborated to develop this comprehensive, pregnancy-specific consensus statement on neuraxial procedures in obstetric patients receiving thromboprophylaxis or higher dose anticoagulants. To date, none of the existing anesthesia societies' recommendations have weighed the potential risks of neuraxial procedures in the presence of thromboprophylaxis, with the competing risks of general anesthesia with a potentially difficult airway, or maternal or fetal harm from avoidance or delayed neuraxial anesthesia. Furthermore, existing guidelines have not integrated the pharmacokinetics and pharmacodynamics of anticoagulants in the obstetric population. The goal of this consensus statement is to provide a practical guide of how to appropriately identify, prepare, and manage pregnant women receiving thromboprophylaxis or higher dose anticoagulants during the ante-, intra-, and postpartum periods. The tactics to facilitate multidisciplinary communication, evidence-based pharmacokinetic and spinal epidural hematoma data, and Decision Aids should help inform risk-benefit discussions with patients and facilitate shared decision making.

Preventing HIV With PrEP.

In this JAMA Patient Page, the US Preventive Services Task Force provides a guide to determine patient risk for HIV, who should take PrEP, and which PrEP strategies are recommended.

Are Centers for Disease Control and Prevention Guidelines for Preexposure Prophylaxis Specific Enough? Formulation of a Personalized HIV Risk Score for Pre-Exposure Prophylaxis Initiation.

BACKGROUND: Preexposure prophylaxis (PrEP) has emerged as a human immunodeficiency virus (HIV) prevention tool for populations at highest risk for HIV infection. Current US Centers for Disease Control and Prevention (CDC) guidelines for identifying PrEP candidates may not be specific enough to identify gay, bisexual, and other men who have sex with men (MSM) at the highest risk for HIV infection. We created an HIV risk score for HIV-negative MSM based on Syndemics Theory to develop a more targeted criterion for assessing PrEP candidacy. METHODS: Behavioral risk assessment and HIV testing data were analyzed for HIV-negative MSM attending the Los Angeles LGBT Center between January 2009 and June 2014 (n = 9481). Syndemics Theory informed the selection of variables for a multivariable Cox proportional hazards model. Estimated coefficients were summed to create an HIV risk score, and model fit was compared between our model and CDC guidelines using the Akaike Information Criterion and Bayesian Information Criterion. RESULTS: Approximately 51% of MSM were above a cutpoint that we chose as an illustrative risk score to qualify for PrEP, identifying 75% of all seroconverting MSM. Our model demonstrated a better overall fit when compared with the CDC guidelines (Akaike Information Criterion Difference = 68) in addition to identifying a greater proportion of HIV infections. CONCLUSIONS: Current CDC PrEP guidelines should be expanded to incorporate substance use, partner-level, and other Syndemic variables that have been shown to contribute to HIV acquisition. Deployment of such personalized algorithms may better hone PrEP criteria and allow providers and their patients to make a more informed decision prior to PrEP use.

Executive summary: Pre-exposure prophylaxis for prevention of HIV infection in adults in Spain: July 2016.

Administration of antiretroviral drugs to individuals exposed to, but not infected by, HIV has been shown to reduce the risk of transmission. The efficacy of pre-exposure prophylaxis (PrEP) makes it obligatory to include it in an integral program of prevention of HIV transmission, together with other measures, such as use of the condom, training, counseling, and appropriate treatment of infected individuals. In this document, the AIDS Study Group (GeSIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [SEIMC]) provides its views on this important subject. The available evidence on the usefulness of PrEP in the prevention of transmission of HIV is presented, and the components that should make up a PrEP program and whose development and implementation are feasible in Spain are set out.

General lack of use of placebo in prophylactic, randomised, controlled trials in adult migraine. A systematic review.

BACKGROUND: The Clinical Trials Subcommittee of the International Headache Society (IHS) recommends that a placebo arm is included in comparative randomised clinical trials (RCTs) of multiple prophylactic drugs due to the highly variable placebo response in migraine prophylaxis studies. The use of placebo control in such trials has not been systematically assessed. METHODS: We performed a systematic review of all comparative RCTs of prophylactic drug treatment of migraine published in English from 2002 to 2014. PubMed was searched using the Cochrane Highly Sensitive Search Strategy for identifying reports of RCTs. RESULTS: A placebo arm was used in <10% (three of 31) of prophylactic RCTs in migraine. In only 7.1% (two of 28) of the comparative RCTs without placebo was one drug superior to another drug. Thus in 26 RCTs, including one study requiring more than 75,000 patient days, no difference was identified across treatment arms and conclusions regarding drug superiority could not be drawn. CONCLUSIONS: The majority of comparative, prophylactic migraine RCTs do not include a placebo arm. Failure to include a placebo arm may result in failure to demonstrate efficacy of potentially effective migraine-prophylactic agents. In order to benefit current and future patients, the current strong tendency to omit placebo-controls in these RCTs should be replaced by adherence to the guidelines of the IHS.

Prophylaxis and treatment recommendations for sinusoidal obstruction syndrome in adult and pediatric patients undergoing hematopoietic stem cell transplant: a review of the literature.

Sinusoidal obstruction syndrome, a complication occurring early after hematopoietic stem cell transplantation, is a concern for clinicians. There are no guidelines to direct clinicians on the optimal way to prevent and treat this disease. Newer data show that defibrotide is a promising drug both for prevention and treatment, although it is not yet FDA approved.

Total intravenous anaesthesia versus single-drug pharmacological antiemetic prophylaxis in adults: A systematic review and meta-analysis.

BACKGROUND: Postoperative nausea and vomiting (PONV) are among the most unfavourable anaesthetic outcomes attributed to the administration of inhaled anaesthetics. Accordingly, inhaled anaesthetics are frequently substituted by propofol when patients are at risk of PONV. As, on some occasions, inhalational anaesthesia may be favourable, the relative impact of propofol anaesthesia needs to be established based on robust data. OBJECTIVE: To compare the effectiveness of a single-drug pharmacological prophylaxis with total intravenous anaesthesia (TIVA) for prevention of PONV. DESIGN: Systematic review of randomised controlled trials with meta-analyses. DATA SOURCES: All available studies until 29 April 2015 were retrieved from MEDLINE, CENTRAL and EMBASE. ELIGIBILITY CRITERIA: Randomised controlled trials on adult patients undergoing general anaesthesia with at least one group receiving propofol-based intravenous anaesthesia without further antiemetic prophylaxis, and one group receiving inhalational anaesthesia with single-drug antiemetic prophylaxis. RESULTS: Fourteen studies involving 2051 patients were included. Compared with TIVA, after inhalational anaesthesia and single-drug antiemetic prophylaxis, there was no difference in the overall risk of PONV [relative risk (RR) 1.06, 95% confidence interval (CI) 0.85; 1.32, GRADE rating moderate], nor was there any difference in the risk of postoperative vomiting (RR 1.17, 95% CI 0.78; 1.76), need for rescue medication (RR 1.16, 95% CI 0.68; 1.99) or early PONV (RR 1.06, 95% CI 0.88; 1.27). However, TIVA was associated with an increased risk of late PONV (RR 1.41, 95% CI 1.10; 1.79, P = 0.006). Six studies investigated other side-effects associated with anaesthesia and found no differences between the two groups. Finally, there was evidence of a publication bias that included smaller studies favouring TIVA. CONCLUSION: This meta-analysis confirms the results from indirect comparisons in individual studies: instead of substituting inhalational anaesthesia with propofol-based TIVA, a similar antiemetic effect can be achieved by adding single-drug pharmacological prophylaxis to the inhalational anaesthetic. STUDY REGISTRATION: This systematic review with meta-analysis was registered at PROSPERO (www.crd.york.ac.uk/PROSPERO), study number CRD42015019571.

Prophylaxis and management of acute radiation-induced skin toxicity: a survey of practice across Europe and the USA.

Radiation-induced toxicity is a common adverse side effect of radiation therapy. Previous studies have demonstrated a lack of evidence to support common skincare advice for radiotherapy patients. The aim of the current study was to investigate the management of radiation-induced skin toxicity across Europe and the USA. Where previous surveys have focused on national practice or treatment of specific sites, the current study aimed to gain a broader representation of skincare practice. An anonymous online survey investigating various aspects of radiotherapy skincare management was distributed to departments across Europe and the USA (n = 181/737 responded i.e. 25%). The UK was excluded as a similar survey was carried out in 2011. The results highlight the lack of consistency in both the prevention and management of radiation-induced skin toxicity. Recommended products are often not based on evidence-based practice. Examples include the continued use of aqueous cream and gentian violet, as well as the recommendations on washing restrictions during treatment. To our knowledge, this is the most extensive survey to date on the current management of radiation-induced skin toxicity. This study highlights significant disparities between clinical practice and research-based evidence published in recent systematic reviews and guidelines. Ongoing large prospective randomised trials are urgently needed.

Exploratory survey of Florida pharmacists' experience, knowledge, and perception of HIV pre-exposure prophylaxis.

OBJECTIVE: To assess Florida pharmacists' experience, knowledge, and perception of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) and to identify areas for pharmacist training. DESIGN: Cross-sectional survey. SETTING: Florida in March through July 2013. PARTICIPANTS: Florida pharmacists. INTERVENTION: In-person and online anonymous survey. MAIN OUTCOME MEASURE: Florida pharmacists' experience, knowledge, and perceptions of PrEP. RESULTS: 225 completed surveys were analyzed. Survey respondents were predominantly community pharmacists with mean age of 45.7 years and less than 20 years of experience. Only 22% of respondents reported dispensing PrEP to patients. Although 75% had completed HIV-related continuing education in the last 2 years, 63% were unaware of Centers for Disease Control and Prevention PrEP guidelines and 71% answered that they did not have sufficient knowledge to counsel patients with PrEP prescriptions. Importantly, 47% of respondents answered they were uncomfortable counseling patients about PrEP. By self-report, most pharmacists agreed PrEP leads to risky behavior (68%) and increased rates of sexually transmitted infections (65%), and is too costly to promote patient access (92%). CONCLUSION: Surveyed Florida pharmacists reported limited understanding of PrEP. As a widely accessible health care counseling resource, pharmacists are positioned to improve patient understanding, promote medication adherence, and enhance PrEP efficacy. Especially during PrEP implementation, when patients may receive PrEP prescriptions from non-HIV specialist prescribers, improving pharmacists' PrEP education presents a salient opportunity.