Post-exposure Prophylaxis Regimens Research Articles

Scoping Review of Pre-Exposure Prophylaxis and Post-Exposure Prophylaxis in HIV Prevention in Türkiye

Abstract Background Pre-Exposure Prophylaxis (PrEP) is a medical -antiretroviral- prevention method that reduces the risk of HIV transmission during sexual intercourse or injection drug use. Post-exposure prophylaxis (PEP) refers to taking medicine after risky exposure. The European Centre for Disease Prevention and Control (ECDC) has recommended the integration of PrEP into the existing HIV prevention packages since 2015. In Türkiye, first PrEP Guideline was published in 2022. The aim of this study is to evaluate the literature gap on the PrEP and PEP for HIV prevention research in Türkiye. Methods This study was conducted in October 2023. Searches were performed using the keywords ‘HIV, AIDS’ and ‘Pre-exposure prophylaxis, PrEP, Post-exposure prophylaxis, PEP’ in PubMed, Web of Science, Scopus, TRDizin, and Dergipark for all years. ‘Türkiye, Turkey, Turkish’ were added into the keywords in international indexes, without using country filters. Inclusion criteria were research on PrEP or PEP for HIV, research conducted in or using data from Türkiye, publications in English/Turkish. Exclusion criteria were non-HIV topics, non-Turkish data, non-English/Turkish publications. Lists were merged, duplicates were removed. Inclusion-exclusion criteria were conducted at title and abstract level. Full texts of the included articles examined for bibliometric characteristics, study types, and key results. Results 1014 publications yielded, 993 evaluated, and 17 fully reviewed. Four discussed Türkiye’s PrEP practices (2018-2023); three analyzed PEP regimens; three were reviews on PrEP/PEP in Türkiye (2016-2022). Two original research articles explored PrEP awareness among Türkiye’s men having sex with men (2022) and infectious disease physicians’ attitudes toward PrEP (2020). Studies showed gaps in PrEP information and service access. Conclusions There are limited studies published on PrEP and PEP in HIV prevention in Türkiye. This study highlights the need for local research on the topic. Key messages • Evaluation of Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP) publications highlights gaps in HIV prevention research. • Limited literature on PrEP and PEP in HIV prevention emphasizing the need for further studies and improved access to PrEP information.

Safety of single-dose bedaquiline combined with rifampicin for leprosy post-exposure prophylaxis: A Phase 2 randomized non-inferiority trial in the Comoros Islands.

To reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP). From July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) <450 ms and liver enzyme tests (ALT/AST) below 3× the upper limit of normal (ULN), before they were individually randomized 1:1 in an open-label design. Recruitment was sequential, by age group. Pediatric dosages were weight adjusted. Follow-up was done at day 1 post-dose (including ECG) and day 14 (including ALT/AST), with repeat of ALT/AST on the last follow-up at day 30 in case of elevation on day 14. The primary outcome was non-inferiority of BE-PEP based on a <10 ms difference in QTc 24 h after treatment administration, both unadjusted and adjusted for baseline QTc. Of 408 screened participants, 313 were enrolled, starting with 187 adults, then 38 children aged 13 to 17 years, and finally 88 children aged 5 to 12 years, of whom 310 (99%) completed all visits. Across all ages, the mean QTc change on BE-PEP was from 393 ms to 396 ms, not significantly different from the change from 392 ms to 394 ms on SDR-PEP (difference between arms 1.8 ms, 95% CI -1.8, 5.3, p = 0.41). No individual's QTc increased by >50 ms or exceeded 450 ms after PEP administration. Per protocol, all children were analyzed together, with no significant difference in mean QTc increase for BE-PEP compared to SDR-PEP, although non-inferiority of BE-PEP in children was not demonstrated in unadjusted analysis, as the upper limit of the 95% CI of 10.4 ms exceeded the predefined margin of 10 ms. Adjusting for baseline QTc, the regression coefficient and 95% CI (3.3; -1.4, 8.0) met the 10 ms non-inferiority margin. No significant differences in ALT or AST levels were noted between the intervention and control arms, although a limitation of the study was false elevation of ALT/AST during adult recruitment due to a technical error. In both study arms, one serious adverse event was reported, both considered unlikely related to the study drugs. Dizziness, nausea, headache, and diarrhea among adults, and headaches in children, were nonsignificantly more frequently observed in the BE-PEP group. In this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampicin is comparable to rifampicin alone, although non-inferiority of QTc changes was demonstrated in children only after adjusting for the baseline QTc measurements. A Phase 3 cluster randomized efficacy trial is currently ongoing in the Comoros. ClinicalTrials.gov NCT05406479.

Occupational post-exposure prophylaxis among healthcare workers: a scoping review of factors affecting optimal utilization.

Post-exposure prophylaxis (PEP) is an efficacious prevention method when initiated promptly after an HIV exposure. Yet, PEP has been underutilized, even among healthcare workers (HCWs) with occupational exposure in sites with PEP policies and procedures and access to PEP medications. It is important to understand the dynamics of uneven PEP use in what appears to be an optimal context to better protect the health and wellbeing of HCWs. We conducted a scoping review to elucidate factors influencing HCWs' use of PEP after occupational exposure. We searched PubMed, PsychInfo and Google Scholar for peer-reviewed literature published in English from 2014 to 2022 using the terms HIV, postexposure/post-exposure prophylaxis, acceptability, healthcare workers, and values and preferences. An inductive narrative review of the resulting 53 studies identified core themes. Nearly all studies (96%) with various HCW types and settings occurred in low- and middle-income countries (LMICs) in Africa and Asia. Identified themes arrayed along a trajectory of PEP use experience: awareness/knowledge; acceptability; availability/access; uptake/use; adherence/completion. Across studies, awareness of PEP for HIV prevention was high, knowledge about drug regimens and healthcare facility policies was moderate to low; acceptability of PEP was moderate to high; PEP's perceived accessibility/availability was inconsistent and varied by geographic location and setting; HCWs' uptake of PEP was low, affected by not knowing how to report an exposure and being unaware of PEP availability; and adherence/completion of PEP regimens was moderate to low, impeded by side effects and a belief that completing regimens was unnecessary to avert seroconversion. HCWs consistently expressed concern about HIV stigma. Findings are limited by the inconsistent use of constructs across studies and a lack of clarity about reporting exposure events. Multi-level approaches are needed to address the interplay of individual, social and structural barriers that diminish HCWs' PEP use. Improved training, incident reporting, 24-hour access to non-stigmatizing PEP services and monitoring of adherence/completion are essential to optimizing HCWs' PEP use. Lessons from HCWs' experience in LMICs may inform understanding of PEP under-use among people in these settings with non-occupational exposures.

Immunogenicity of 4-dose Essen intramuscular regimen for rabies post-exposure prophylaxis: A multi-center cross-sectional study in China

BackgroundThe 4-dose Essen intramuscular (IM) regimen for rabies post-exposure prophylaxis (PEP) has been recommended by Advisory Committee on Immunization Practices (ACIP) and World Health Organization (WHO), but the large-sample clinical evidence is still limited. MethodRabies virus neutralizing antibodies of 11,752 patients were detected from 409 rabies prevention clinics in 27 provinces in China. Patients with serum collected before or no later than 1 h after injection on the day of the fifth dose (day 28) of 5-dose Essen regimen were included in Group A to observe the immune efficacy of 4-dose Essen IM regimen, and patients with serum collected 14–28 days after injection of the fifth dose were included in Group B to observe the immune efficacy of 5-dose Essen IM regimen. ResultsFinally, 2351 cases met the inclusion and exclusion criteria, including 2244 cases in Group A and 107 cases in Group B. The antibody titer of Group A was higher than that of Group B [12.21 (4.15, 32.10) IU/ml vs. 9.41 (3.87, 27.38) IU/ml] (P = 0.002). In Group A, the median antibody titers were 4.01IU/ml, 11.63IU/ml and 29.46IU/ml in patients vaccinated with purified hamster kidney cell vaccine (PHKCV), purified Vero cell vaccine (PVRV), and human diploid cell rabies vaccine (HDCV), respectively, with statistical significance (P < 0.001). ConclusionsThe 4-dose Essen IM regimen could provide satisfactory immune effect, and HDCV induced higher antibody titer than PHKCV or PVRV.

Postexposure prophylaxis for occupational exposure to selected pathogens for healthcare personnel.

Timely postexposure prophylaxis is important after an occupational exposure. Here we review select organisms, exposure opportunities in the healthcare setting, and postexposure prophylaxis regimens. Needlestick injuries pose a risk of exposure to bloodborne pathogens, such as HIV, Hepatitis B, and Hepatitis C. Risk mitigation strategies should be reexamined in light of newer vaccines and therapeutics. Increased vaccine hesitancy and vaccine denialisms may foster the re-emergence of some infections that have become extremely uncommon because of effective vaccines. With increasing occurrences of zoonotic infections and the ease of global spread as evidenced by COVID-19 and mpox, healthcare exposures must also consider risks related to emerging and re-emerging infectious diseases. Early recognition and reporting of occupational exposures to pathogens with available postexposure prophylaxis is key to mitigating the risk of transmission. Providers should be able to evaluate the exposure and associated risks to provide prompt and appropriate postexposure prophylaxis.

Safety and adherence of bictegravir/emtricitabine/tenofovir alafenamide for HIV post-exposure prophylaxis among adults in Guiyang China: a prospective cohort study

BackgroundThe effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens.MethodsIn this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG).ResultsThe PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events.ConclusionsBIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes.Trial registrationThe study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391).

A phase 2b, Randomized, double blinded comparison of the safety and efficacy of the monoclonal antibody mixture SYN023 and human rabies immune globulin in patients exposed to rabies

BackgroundSYN023 is an anti-rabies monoclonal antibody mixture administered as part of post-exposure prophylaxis regimens. The rabies virus neutralizing antibody (RVNA) concentration generally accepted as an adequate immune response to vaccination is ≥ 0.5 IU/mL. MethodsWithin 54 h of potential rabies exposure, 448 patients in two risk substrata of WHO Category III exposure were randomized to receive either 0.3 mg/kg SYN023 or 0.133 mL/kg human rabies immunoglobulin (HRIG) injected in and around the wound site(s) plus a course of rabies vaccination. Patients were followed for safety and absence of rabies for ≥ 365 days. ResultsGMT RVNA was higher with SYN023 throughout the 2-week post-treatment period. In the primary analysis group (n = 368), 99.4 % of SYN023 recipients versus 4.5 % of HRIG recipients had protective RVNA levels on Day 4. On Day 8, 98.1 % SYN023 versus 12.2 % HRIG recipients were protected. The SYN023:HRIG ratio of geometric mean titer of RVNA (RVNA GMTs) on Day 8 (19.42) exceeded the 10 % superiority margin (P < 0.0001) indicating higher Day 8 RVNA with SYN023. On Day 99, the SYN023:HRIG RVNA GMT ratio (0.66) was below the non-inferiority margin of 20 % (P = 0.9485) suggesting some moderation of vaccine immune response by SYN023 relative to HRIG. The ratio of percent SYN023:HRIG recipients achieving RVNA ≥ 0.5 IU/mL on Day 99 (0.98) met the non-inferiority margin of 20 % (P = 0.013) indicating anti-rabies immune response with SYN023 was non-inferior to HRIG despite this effect. There were no probable/confirmed rabies cases in any patient. Study regimens were well tolerated. ConclusionsSYN023 provided higher RVNA than HRIG soon after rabies exposure. By Day 99 post-treatment, GM RVNA with SYN023 was lower than HRIG, however, the percent of SYN023 recipients with a protective response was not inferior at this time point. No rabies cases were reported in the study. The SYN023 safety profile was acceptable.ClinicalTrials.gov ID: NCT03961555.

Immunogenicity and Safety of a Purified Vero Rabies Vaccine-Serum Free, Compared With 2 Licensed Vaccines, in a Simulated Rabies Post-Exposure Regimen in Healthy Adults in France: A Randomized, Controlled, Phase 3 Trial.

A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman-Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab) and the human diploid cell vaccine (HDCV; Imovax Rabies®). This dual-center, modified, double-blind, phase 3 study evaluated the immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG) versus PVRV + HRIG and HDCV + HRIG in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N = 640) were randomized 3:1:1:1 to PVRV-NG2 + HRIG, PVRV + HRIG, HDCV + HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, D3, D7, D14, and 28, with HRIG on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA) titers were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2 + HRIG and PVRV + HRIG/HDCV + HRIG was >-5% at D28. Safety was assessed up to 6 months after the last injection. Non-inferiority of PVRV-NG2 + HRIG compared with PVRV + HRIG and HDCV + HRIG was demonstrated. Nearly all participants (99.6%, PVRV-NG2 + HRIG; 100%, PVRV + HRIG; 98.7%, HDCV + HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines. In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines. NCT03965962.

The PEP++ study protocol: a cluster-randomised controlled trial on the effectiveness of an enhanced regimen of post-exposure prophylaxis for close contacts of persons affected by leprosy to prevent disease transmission

BackgroundLeprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP.MethodsThe PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 − 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 − 600 mg) and clarithromycin (150 − 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox’ proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome.DiscussionPast studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities.Trial registrationNL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060

Real-world evidence of rabies post-exposure prophylaxis in Serbia: Nation-wide observational study (2017–2019)

BackgroundRabies remains a deadly zoonotic disease, primarily prevalent in Eastern European countries, with a significant global burden in Asia and Africa. Post-exposure prophylaxis (PEP) is critical to prevent clinical rabies. Serbia, a country with a relatively low animal rabies incidence, has been implementing a 4-dose Essen PEP regimen for 13 years. This real-world study aimed to assess the effectiveness of the 4-dose Essen regimen, considering demographic and clinical factors, after WHO Category III exposure. MethodThe study included 601 patients who received the 4-dose Essen PEP and 79 who received an additional 5th dose. ResultsAge emerged as a critical factor influencing seroconversion rates after the 4-dose regimen, with older individuals exhibiting lower RVNA titers. Logistic regression indicated a 3.18% decrease in seroconversion odds for each added year of age. The Cox proportional hazards mixed model highlighted age-related risks, with age groups 45–60 and 75–92 at the highest risk of non-seroconversion. Human Rabies Immune Globulin (HRIG) administration was associated with lower RVNA values after the 4-dose regimen, suggesting interference with vaccine immunogenicity among people who received larger doses of HRIG. ConclusionsThis study provides valuable real-world evidence for rabies PEP in a non-homogeneous population with potential comorbidities. The results underscore the importance of optimizing PEP strategies, particularly in older individuals, and reconsidering HRIG dosing to improve seroconversion rates.

Compatible co-administration of BioThrax® vaccine and ciprofloxacin—Results of a randomized open-label drug-vaccine interaction trial

The recommended treatment for post-exposure prophylaxis (PEP) following known/suspected exposure to Bacillus anthracis involves immunization with anthrax vaccine adsorbed (AVA, i.e., BioThrax® vaccine) and a course of antimicrobial therapy. A drug-vaccine interaction clinical trial was conducted to determine whether this combined treatment might modify antimicrobial exposure or vaccine immunogenicity.A Phase 2, randomized, open-label, multi-center trial involving 154 healthy adult participants was completed to evaluate the effect of AVA immunization (three doses administered subcutaneously (SC) at weeks 0, 2 and 4) on the pharmacokinetics (PK) of ciprofloxacin, as well as the effect of ciprofloxacin administration (500 mg po bid) on the immunogenicity of AVA. PK parameters were derived using noncompartmental analysis of ciprofloxacin serum concentrations. Immunogenicity was assessed using a toxin neutralizing antibody (TNA) assay resulting in 50 % neutralization factor (NF50) values. Safety was assessed via reports of adverse events (AEs), clinically significant changes in laboratory parameters and vital signs, and collection of solicited local and systemic reactogenicity reactions.Statistical analyses of the steady state (SS) and single dose PK parameters Cmax and AUC0-–12h indicated that the AVA PEP regimen did not significantly modify ciprofloxacin exposure. Comparison of the geometric mean TNA NF50 values between participants receiving AVA + ciprofloxacin and those receiving AVA alone showed that the combined treatment was non-inferior to AVA alone. The trial met all prospectively defined success criteria for the primary PK endpoint and for the secondary PK and immunogenicity endpoints. There were no deaths, SAEs or AEs leading to drug discontinuation or study withdrawal during the trial.Overall, concomitant administration of ciprofloxacin and AVA produced no significant changes in the PK profile of ciprofloxacin nor in the immunogenicity of AVA. Furthermore, this trial demonstrated that the co-administration of ciprofloxacin and AVA was well tolerated in healthy adult participants.

Post-Exposure Prophylaxis for Varicella-Zoster Virus Exposure in High-Risk Children.

Post-exposure prophylaxis (PEP) with varicella immunoglobulin is recommended to minimize risk of varicella complications for high-risk children. However, providers frequently use alternatives like acyclovir or intravenous immunoglobulin. A retrospective cohort study was conducted of PEP for varicella in children from January 2009 to December 2019. Data were provided by 47 children's hospitals who participate in the Pediatric Health Information Systems database. Patients with clinical encounters for varicella exposure were reviewed. Choice of varicella PEP regimens, including differences by underlying condition and institution, and incidence of varicella disease were determined. A total of 1704 patients with first clinical encounters for varicella met inclusion criteria. Of these patients, 509 (29.9%) were prescribed PEP after varicella exposure, and 65 (3.8%) ultimately had a subsequent encounter for varicella disease. Of 509 patients who received PEP, acyclovir was most frequently prescribed (n = 195, 38.3%), followed by varicella immunoglobulin (n = 146, 28.7%), IVIG (n = 115, 22.6%), and combination therapy (n = 53, 10.4%). The highest proportion of varicella immunoglobulin use (10/20, 50%) was amongst children with diagnoses of rheumatological/gastrointestinal conditions. The highest proportion of acyclovir use (29/684, 4.2%) was amongst children with diagnoses of oncology/stem cell transplant conditions. The proportion of patients who subsequently had clinical encounters for varicella disease was highest for Acyclovir (30/195, 15.4%) followed by varicella immunoglobulin (5/146, 3.4%), combination therapy (2/53, 3.8%), and intravenous immunoglobulin alone (0/115) (P < .0001). Varicella PEP in high-risk children was highly varied among children's hospitals. In our dataset, use of acyclovir was associated with a higher rate of subsequent encounters for Varicella disease.

Specialty pharmacy interventions benefit patients receiving HIV postexposure prophylaxis

BackgroundSpecialty pharmacies service many different complex disease states that require high-cost medication, including the treatment of patients prescribed human immunodeficiency virus postexposure prophylaxis (PEP). PEP requires time-sensitive initiation and patient counseling for therapeutic efficacy. ObjectiveThis study aimed to examine all PEP referrals received at a specialty pharmacy and demonstrate how they aided in interventions including assisting in obtaining financial assistance, making clinical interventions, and offering counseling to patients. MethodsThis is an observational retrospective chart review of patients who received PEP from one specialty pharmacy. All patients who filled PEP at the pharmacy between January 1, 2017, and July 1, 2022, were included. Information was collected from documentation provided in the electronic medication record used by the pharmacy. The PEP regimen prescribed were raltegravir (RAL) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and dolutegravir (DTG) + FTC/TDF. ResultsA total of 52 patients were treated with PEP during the measurement period. Patients who received a PEP regimen of RAL + FTC/TDF experienced a total cost savings of $1692.60 and $218.40 for those who were fully insured and uninsured, respectively. Patients who received a PEP regimen of DTG + FTC/TDF experienced a total cost savings of $676.20 and $2725.50 for those who were fully insured and uninsured, respectively. Counseling by a pharmacist was offered to all patients and 74.5% of patients accepted. Pharmacists made clinical interventions on 29.4% of PEP referrals. ConclusionPEP medications are expensive and time sensitive and can require clinical interventions and specific patient counseling. This study indicates that specialty pharmacies can provide and ensure access to care in the areas of financial assistance, patient counseling, and clinical interventions.

Rabies experts on demand: A cross-sectional study describing the use of a rabies telehealth service.

Rabies expert on demand (REOD) telehealth service is provided by the U.S. Centers for Disease Control and Prevention (CDC) to assist public health practitioners, health providers, and the public to interpret national and international rabies prevention guidelines. REOD is staffed by subject matter experts of the CDC Poxvirus and Rabies Branch to assess each unique situation and provide evidence-based guidance to stakeholders. This study aims to describe the utilization of a rabies telehealth system and provide insight into common consultations. A cross-sectional study of the nature of inquiries to REOD was done using the data collected from September 1, 2017 to September 30, 2021. An inquiry tracking form and Microsoft Access database were developed to document all inquiries received. Inquired ones were summarized to determine the frequency of inquiries by month, category, and location. Over a 49-month period, REOD received 5228 inquiries. Peak inquiries (n = 108) occurred during August 2019. The most frequent inquiries received pertained to risk assessment and management of rabies exposures (n = 1109), requests for testing assistance (n = 912), consultation for suspected human rabies (n = 746), rabies exposures and post-bite treatment occurring internationally (n = 310), and consultation for deviations in the recommended pre- and postexposure prophylaxis regimen (n = 300). REOD is a global resource for consultation related to managing rabies exposures, diagnostic issues, and rabies control strategies. REOD is a regularly utilized CDC service, as the demand for up-to-date rabies guidance remains high. REOD fulfills a critical role for the interpretation and consultation on rabies prevention guidelines to stakeholder.

Active safety surveillance of rabies monoclonal antibody and rabies vaccine in patients with category III potential rabies exposure.

A vero cell-based inactivated Rabies Vaccine (Rabivax-S) and Rabies Human Monoclonal Antibody (Rabishield) have been approved since 2016. A post-marketing surveillance was conducted in India from 2020 to 2021 to gather real world safety data on Rabivax-S and Rabishield. This was non-interventional active surveillance in patients with category III potential rabies exposure who were administered a post-exposure prophylaxis (PEP) regimen (Rabishield and Rabivax-S) by their healthcare providers (HCPs) as per the dosages and regimens mentioned in the package insert approved by the Indian regulators. The approved schedule for PEP was local infiltration of Rabishield on Day 0 and five doses of Rabivax-S on Day 0, 3, 7, 14, and 28 (Intramuscular route, IM) or four doses of Rabivax-S on Day 0, 3, 7, and 28 (Intradermal route, ID). The primary objective of this surveillance was to generate real-world evidence on the safety and tolerability of Rabishield and Rabivax-S. All patients enrolled in the surveillance were required to report any adverse events (AEs) occurring up to Day 31 after initiation of PEP (administration of Rabishield and the first dose of Rabivax-S) to their HCP. A total of 1000 patients with category III potential rabies exposure were enrolled across India. 991 patients received the PEP regimen with IM Rabivax-S while 9 received a PEP regimen with the ID regimen. While 32% of the patients were <12 years of age, 11.8% were ≥12 to <18 years of age and 56.2% were ≥18 years of age. The entire PEP regimen was completed by 97.3% of the enrolled patients. A total of 69 AEs were reported in 64 patients. Out of these, 49 AEs in 47 patients were assessed as causally related to the study products (26 with Rabishield and 23 with Rabivax-S). The majority of the AEs were mild and all recovered without any sequelae. One serious adverse event (SAE) of fracture of the hand was reported which was not related to either Rabishield or Rabivax-S. No case of rabies was reported. Rabishield and Rabivax-S have an excellent safety profile and are well tolerated. No participant developed rabies during 31 day follow up. The PMS was funded by Serum institute of India Private Limited which is the manufacturer of the study products.

Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.

All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.

Cost analysis of implementation of a population level rabies control programme for children in India

BackgroundRabies is an endemic and major public health problem in India. This paper reports cost of implementation of various Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP) strategies at programmatic level to avert rabies deaths in children in India. MethodsThe cost of implementation of various PrEP + PEP and PEP only regimens recommended by WHO and national guidelines was calculated separately for the first year of implementation for children in the age group of 0–5 years (U-5) and 5–15 years (U-15). The cost was calculated at the level of health facility from government's perspective considering the implementation of the strategies under National Rabies Control Program. All costs were converted into 2020 Indian National Rupee and International Dollars' value using implicit price deflators for Purchasing Power Parities. Base case, scenario and one-way sensitivity analyses were conducted. ResultsThe cost of implementation of PrEP regimen is several times higher than all other PEP regimens in children in the age groups of 0–5 years and 5–15 years for the first year of implementation. However, the study also reported use of intradermal route of vaccination and local infiltration of ERIG in wounds only as a cost-saving approach to prevent rabies deaths in children in situations where PEP only strategies are implemented. ConclusionsThere is a need to conduct primary studies in order to obtain data for cost of implementation of shorter regimens in real-time settings.

Scenario of HIV infection in Pakistan

Human immunodeficiency virus (HIV) infection, which was previously lethal, has evolved into a chronic disease that may be treated and well-managed. HIV levels in the bloodstream may become undetectable with antiretroviral therapy (ART). All those providing care for people living with HIV should be aware of the risk factors, transmission, diagnosis, and treatment, acute HIV infection, possible opportunistic infections, and malignancies. Preexposure and postexposure prophylaxis regimens allow for preventive treatment. Home healthcare specialists can help people follow their drug schedules, assess the effectiveness of their treatments, and identify HIV problems and ART side effects. The ability to support, inform, and counsel people living with HIV and their families is most crucial [1].&#x0D; Approximately 38.9 million people worldwide were living with HIV, 25.4 million had access to antiretroviral therapy (ART), 1.7 million had just recently contracted the virus, and 690,000 had passed away from AIDS-related illnesses, according to a Joint United Nations Program on HIV/AIDS 2020 report. Although Pakistan's national HIV/AIDS control program was established in 1987, the number of new HIV/AIDS cases has been rising quickly ever since. In Pakistan, 160,000 people were living with HIV/AIDS as of 2018, yet only 10% of them were receiving ART. 3 Increasing people with HIV/AIDS' access to ART has a number of positive effects, including delaying the advancement of the disease, extending life expectancy, and enhancing people's quality of life and mental health [2].&#x0D; "More than 1,000 new HIV cases are reported each month from all four provinces, including the capitol city Islamabad, Azad Kashmir, and Gilgit Baltistan. This demonstrates unequivocally that homosexuals, persons who inject drugs, male, female, and transgender sex workers, and other critical demographics are now spreading HIV to the broader community. During the final 10 months of 2022, 9,773 people in Pakistan had HIV tests that were positive, casting significant doubt on HIV preventive and control initiatives and amply demonstrating the spread of HIV from important populations to the general public. New HIV infections account for a sizable portion of low-risk males, females, and clients of critical communities, showing an increase in HIV transmission to bridging populations [3].&#x0D; The increased rate of HIV in Pakistan pose a risk to a healthy population, blood recipients etc. Therefore, surrounding communities should also be checked for HIV. The government should direct public education campaigns in coordination with NGOs. To prevent any future epidemics, barbers and unlicensed health professionals in remote regions should receive training.

Survival of 21 Dogs after Post-exposure Prophylaxis using Intra-dermal Rabies Vaccine in the Pre-scapular Region and Emergency Use of Expired Equine Rabies Immunoglobulin for Local Wound Infiltration in Victims of a Rabid Dog Bite using One Health Approach

Rabies is a 100% fatal zoonotic disease and is preventable through timely and adequate Post-Exposure Prophylaxis (PEP). World Organization for Animal Health (WOAH) haven’t issued any guidelines for PEP for rabies in animals, still in certain Indian states like Himachal Pradesh (HP) PEP regimen with active immunization on 0,3,7,14 and 28 days mostly by Intramuscular Rabies Vaccine (IMRV) is being followed. Recently in Rampur Bushahar, a suspected rabid dog later laboratory confirmed had bitten 21 dogs, 2 cows, and 2 men. We employed PEP in animals using Raksharab vaccine intra-dermally (IDRV) (0.2 ml, pre-scapular region) on days 0, 3,7,14, and 28 along with only local wound infiltration of eRIG in 8 out of 11 bitten dogs with Category III exposure. Furthermore, 3 noncooperative dogs with Category III exposure were given IMRV (1ml) on day 0,3,7,14,28 with only wound infiltration of eRIG. 2 Cows were administered 0.2 ml IDRV in the skin at the middle of the neck with only wound infiltration of eRIG. Human bite victims also received 0.1 ml IDRV at 2 sites in the deltoid region on days 0,3, and 7 along with wound infiltration of eRIG at the nearby health center. Serum samples were collected for Rapid Fluorescent Focus Inhibition Test (RFFIT) for estimation of Rabies Vaccine Neutralizing Antibody (RVNA) titer after day 14 for 8 dogs, 2 cows, and human bite victims, and all had RVNA titer &gt;0.5 IU/ml on day 14 except one in IMRV group. None of the bitten victims had clinical manifestations of rabies even after 1 year of follow-up. This indicates wound infiltration with eRIG along with the vaccine could be a life-saving protocol. Also using expired eRIG in emergencies was safe and life saving in animals. Expired eRIG used was later tested and was found to be potent.

A Cost-Effectiveness Analysis of Pre-Exposure Prophylaxis to Avert Rabies Deaths in School-Aged Children in India.

Children contribute to one-half of the total painful rabies mortalities in India. The state-of-the-art rabies mortality averting strategies need exploration for the effective implementation of pre-exposure prophylaxis (PrEP) in India. This study reports on the economic evaluation of various PrEP and post-exposure prophylaxis (PEP) strategies to avert rabies mortalities in school-aged children in India. A decision tree model has been developed for children in the age group of 5-15 years to evaluate various PrEP + PEP and PEP only regimens. The 2-site intradermal regimen administered on day zero and seven was chosen as the intervention [PrEP (I)]. ICER was calculated from the quasi-societal and quasi-health systems' perspectives for the base case analysis, along with one-way sensitivity, and scenario analyses for each regimen. The incremental DALYs averted per million population with the implementation of PrEP (I) ranged between 451 and 85,069 in 2020. The ICER was reported in the range of USD 384-352/DALY averted (non-dominant) in comparison to PEP regimens from a quasi-societal perspective. PrEP (I) is reported to be 'very cost effective' in comparison with PEP regimens from the quasi-societal and quasi-health systems' perspectives and reduce deaths by up to 89.9%. This study concludes that the PrEP (I) regimen is a cost-effective and life-saving strategy to avert painful mortalities due to rabies in school-aged children in India.