Adherence to Post-Exposure Prophylaxis (PEP) and Incidence of HIV Seroconversion in a Major North American Cohort.
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ABSTRACT:
SUBMITTER: Thomas R
PROVIDER: S-EPMC4641668 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:IntroductionAntiretroviral-based HIV prevention, including pre-exposure prophylaxis (PrEP), is expanding in generalized epidemic settings, but additional prevention options are needed for individuals with periodic, high-risk sexual exposures. Non-occupational post-exposure prophylaxis (PEP) is recommended in global guidelines. However, in Africa, awareness of and access to PEP for sexual exposures are limited. We assessed feasibility, acceptability, uptake and adherence in a pilot study of a patient-centred PEP programme with options for facility- or community-based service delivery.MethodsAfter population-level HIV testing with universal access to PrEP for persons at elevated HIV risk (SEARCH Trial:NCT01864603), we conducted a pilot PEP study in five rural communities in Kenya and Uganda between December 2018 and May 2019. We assessed barriers to PEP in the population and implemented an intervention to address these barriers, building on existing in-country PEP protocols. We used community leaders for sensitization. Test kits and medications were acquired through the Ministry of Health supply chain and healthcare providers based at the Ministry of Health clinics were trained on PEP delivery. Additional intervention components were (a)PEP availability seven days/week, (b)PEP hotline staffed by providers and (c)option for out-of-facility medication delivery. We assessed implementation using the Proctor framework and measured seroconversions via repeat HIV testing. Successful "PEP completion" was defined as self-reported adherence over four weeks of therapy with post-PEP HIV testing.ResultsCommunity leaders were able to sensitize and mobilize for PEP. The Ministry of Health supplied test kits and PEP medications; after training, healthcare providers delivered the 28-day regimen with high completion rates. Among 124 persons who sought PEP, 66% were female, 24% were ≤25 years and 42% were fisherfolk. Of these, 20% reported exposure with a serodifferent partner, 72% with a new or existing relationship and 7% from transactional sex. 12% of all visits were conducted at out-of-facility community-based sites; 35% of participants had ≥1 out-of-facility visit. No serious adverse events were reported. Overall, 85% met the definition of PEP completion. There were no HIV seroconversions.ConclusionsAmong individuals with elevated-risk exposures in rural East African communities, patient-centred PEP was feasible, acceptable and provides a promising addition to the current prevention toolkit.
| S-EPMC8215805 | biostudies-literature
Project description:The efficacy of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19 was contentious. In this randomized control double-blind clinical trial, asymptomatic individuals with direct contact with laboratory-confirmed COVID-19 cases were randomized into PEP/HCQ (N = 574) and control/placebo (N = 594) group. The PEP/HCQ group received tablet HCQ 400 mg q 12 hourly on day one followed by 400 mg once weekly for 3 weeks, and the control/Placebo group received matching Placebo. The incidence of COVID-19 was similar (p = 0.761) in PEP [N = 24 out of 574, (4.2%)] and control [N = 27 out of 594, (4.5%)] groups. Total absolute risk reduction for the incidence of new-onset COVID-19 was -0.3% points with an overall relative risk of 0.91 (95% confidence interval, 0.52 to 1.60) and the number needed to treat (NNT) was 333 to prevent the incident of one case of COVID-19. The study found that, PEP with HCQ was not advantageous for the prevention of COVID-19 in asymptomatic individuals with high risk for SARS-CoV-2 infection. Though HCQ is a safer drug, the practice of irrational and indiscriminate use of HCQ for COVID-19 should be restrained with better pharmacovigilance.
| S-EPMC9825075 | biostudies-literature
Project description:Many drugs have been tried for the treatment/prevention of COVID-19 with limited success. Direct household contacts of COVID-19 patients are at highest risk for SARS-CoV-2 infection. Hydroxychloroquine (HCQ) has been tried against COVID-19 owing to its in vitro virucidal action against SARS-CoV-2, but the role of HCQ as post-exposure prophylaxis (PEP) remains inconclusive. In this open-label, controlled clinical trial, asymptomatic individuals who had direct contact with laboratory-confirmed COVID-19 cases or had undertaken international travel in the last 2 weeks were offered HCQ prophylaxis and assigned to PEP (n = 132) or control (n = 185) group. The PEP group received HCQ 800 mg on Day 1 followed by 400 mg once weekly for 3 weeks. Both groups undertook home quarantine for 2 weeks along with social distancing and personal hygiene. Over 4-week follow-up, 50/317 participants (15.8%) had new-onset COVID-19. The incidence of COVID-19 was significantly (P = 0.033) lower in the PEP (14/132; 10.6%) compared to the control (36/185; 19.5%) group (total absolute risk reduction, -8.9% points). The NNT to prevent the occurrence of 1 COVID-19 case was 12. Overall relative risk was 0.59 (95% CI 0.33-1.05). Compliance was good. The most common adverse event was epigastric discomfort with burning sensation (three participants), with no serious adverse events. PEP with HCQ has the potential for the prevention of COVID-19 in at-risk individuals. Until definitive therapy is available, continuing PEP with HCQ may be considered in suitable at-risk individuals. Further randomised clinical trials with larger samples are required for better evaluation of HCQ as PEP for COVID-19 prevention.
| S-EPMC7646370 | biostudies-literature
Project description:In Vietnam, rabies has been a notifiable disease for more than 40 years. Over the last five years, on average, more than 350,000 people per year have been bitten by dogs and cats while more than 80 human deaths have been reported yearly. No studies have been conducted to evaluate the geographical and temporal patterns of rabies in humans in Vietnam. Therefore, the main objective of this study was to assess the geographical and temporal distributions of rabies post exposure prophylaxis (PEP) incidence in humans in Vietnam from 2005 to 2015.Average incidence rabies (AIR) PEP rates for every 3 or 4 years (2005-2008, 2009-2012 and 2013-2015) were calculated to describe the spatial distribution of rabies PEP. Hotspot analysis was implemented to identify patterns of spatial significance using the Getis-Ord Gi statistic. For temporal pattern analysis, two regions [Mekong River Delta (MRD) and Southeast Central Coast (SCC)], with the highest incidence rates, and the seasonal-decomposition procedure based on loess (STL), were compared to assess their temporal patterns of rabies PEP.We found hotspots in southern Vietnam and coldspots in northern Vietnam during the study period. Rabies cases were limited to specific areas. In addition, the hotspot analysis showed that new risk areas were identified in each period which were not observed in incidence rate maps. The seasonal plots showed seasonal patterns with a strong peak in February/July and a minor peak in October/December in the MRD region. However, in the SCC, a small peak was detected at the early part of each year and a strong peak in the middle of each year.Our findings provide insight into understanding the geographical and seasonal patterns of rabies PEP in Vietnam. This study provides evidence to aid policy makers when making decisions and investing resources. Such information may also be utilized to raise public awareness to prevent rabies exposures and reduce unnecessary PEP.
| S-EPMC5892892 | biostudies-literature
Project description:With the rise of the second pandemic wave of the novel influenza A (H1N1) virus in the current season in the Northern Hemisphere, pandemic plans are being carefully re-evaluated, particularly for the strategic use of antiviral drugs. The recent emergence of oseltamivir-resistant in treated H1N1 patients has raised concerns about the prudent use of neuraminidase inhibitors for both treatment of ill individuals and post-exposure prophylaxis of close contacts.We extended an established population dynamical model of pandemic influenza with treatment to include post-exposure prophylaxis of close contacts. Using parameter estimates published in the literature, we simulated the model to evaluate the combined effect of treatment and prophylaxis in minimizing morbidity and mortality of pandemic infections in the context of transmissible drug resistance.We demonstrated that, when transmissible resistant strains are present, post-exposure prophylaxis can promote the spread of resistance, especially when combined with aggressive treatment. For a given treatment level, there is an optimal coverage of prophylaxis that minimizes the total number of infections (final size) and this coverage decreases as a higher proportion of infected individuals are treated. We found that, when treatment is maintained at intermediate levels, limited post-exposure prophylaxis provides an optimal strategy for reducing the final size of the pandemic while minimizing the total number of deaths. We tested our results by performing a sensitivity analysis over a range of key model parameters and observed that the incidence of infection depends strongly on the transmission fitness of resistant strains.Our findings suggest that, in the presence of transmissible drug resistance, strategies that prioritize the treatment of only ill individuals, rather than the prophylaxis of those suspected of being exposed, are most effective in reducing the morbidity and mortality of the pandemic. The impact of post-exposure prophylaxis depends critically on the treatment level and the transmissibility of resistant strains and, therefore, enhanced surveillance and clinical monitoring for resistant mutants constitutes a key component of any comprehensive plan for antiviral drug use during an influenza pandemic.
| S-EPMC2794871 | biostudies-other
Project description:To characterize adherence to post-exposure prophylaxis after non-forcible sexual exposure to HIV, we conducted a review of the literature and meta-analysis. Articles were considered if they contained primary adherence data following non-forcible sexual exposure. Random-effects meta-analysis was used to create pooled point estimates for adherence. Of 1,257 abstracts identified through our search algorithm, 17 were eligible for inclusion in this review, representing 3,634 patients enrolled in 3 randomized controlled trials (RCTs), 9 prospective and 5 retrospective observational studies. Pooled adherence, primarily assessed by self-report, was 77 % [95 % confidence interval (CI) 68-87] in prospective observational studies, 81 % (95 % CI 65-96) in retrospective studies, 78 % (95 % CI 65-91) in RCTs, and 78 % (95 % CI 72-85) overall. Overall adherence was moderately high, with high variability between studies. Assessment of adherence could be enhanced by the use of objective measurements.
| S-EPMC3864606 | biostudies-literature
Project description:The incidence of human immunodeficiency virus (HIV) infection continues to rise among core groups and efforts to reduce the numbers of new infections are being redoubled. Post-exposure prophylaxis (PEP) is the use of short-term antiretroviral therapy (ART) to reduce the risk of acquisition of HIV infection following exposure. Current guidelines recommend a 28-day course of ART within 36-72 hours of exposure to HIV. As long as individuals continue to be exposed to HIV there will be a role for PEP in the foreseeable future. Nonoccupational PEP, the vast majority of which is for sexual exposure (PEPSE), has a significant role to play in HIV prevention efforts. Awareness of PEP and its availability for both clinicians and those who are eligible to receive it are crucial to ensure that PEP is used to its full potential in any HIV prevention strategy. In this review, we provide current evidence for the use of PEPSE, assessment of the risk of HIV transmission, indications for PEP, drug regimens, and management of patients started on PEP. We summarize national and international guidelines for the use of PEPSE. We explore the place of PEP within the wider strategy of reducing HIV incidence rates in the era of treatment as prevention and pre-exposure prophylaxis. We also consider the implications of recent data from interventional and observational studies demonstrating significant reductions in the risk of HIV transmission within a serodiscordant relationship if the HIV-positive partner is taking effective ART upon PEP guidelines.
| S-EPMC4216036 | biostudies-other
Project description:Tenofovir diphosphate (TFV-DP) concentrations measured with dried blood spots (DBS) can be used to classify adherence to emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV pre-exposure prophylaxis (PrEP). A TFV-DP of 700 fmol/punch was previously associated with high PrEP efficacy, and was estimated to represent ≥4 doses/week on average. However, interindividual variability in TFV-DP concentrations may lead to adherence misclassification and decrease the precision of adherence-efficacy relationships. The purpose of this analysis was to evaluate sources of TFV-DP variability to improve the precision of TFV-DP for adherence assessments by incorporating individual characteristics. Data and samples from a 36-week study of TFV-DP in DBS, collected biweekly, among 48 HIV-negative volunteers (25 Females/26 Caucasian/10 African American/14 Hispanic) receiving F/TDF at 33%, 67%, and 100% of daily dosing under directly observed therapy were used for analysis. The simplest pharmacokinetic model to describe TFV-DP accumulation with acceptable performance was a one-compartment constant input model. Covariates, including laboratory values and demographics were ranked in importance of their association with post hoc pharmacokinetic (PK) parameters using random forest analyses. Weight and platelet count were included in the final model and simulations were conducted to generate benchmarks for <2, 2-3, 4-5, and 6-7 doses/week. Based on these simulations, the previously established protective TFV-DP concentration of ≥700 fmol/punch was observed in those taking 2-3 (in individuals ≤110 kg) and ≥4 (in individuals >110 kg) doses/week, amounting to a much lower rate of misspecification (17% vs. 30%) with this individualized model versus previous interpretations. Incorporating body weight and platelet count improved the precision of TFV-DP concentrations for adherence assessments. Previous benchmarks were conservative, indicating that the pharmacological forgiveness of F/TDF may be higher than currently recognized and supports continued investigation of intermittent PrEP dosing regimens. Clinical Trial Registration number, NCT02022657.
| S-EPMC8213008 | biostudies-literature
Project description:As pre-exposure prophylaxis (PrEP) effectiveness is strongly linked to adherence, we sought to determine if certain self-report measures could be used to inform objective PrEP adherence. We studied participants from the TAPIR study (a multicenter randomized study of daily text messages to support adherence to PrEP In At-Risk), a 48-week randomized controlled trial of HIV-uninfected men who have sex with men (MSM) randomized to receive text message to support adherence versus standard of care. Self-reported medication adherence was assessed using several validated measures modified for PrEP. Objective PrEP adherence was determined through dried blood spot (DBS) measurement of intracellular tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP). A summary of adherence was estimated using responses to the seven adherence items at weeks 12 and 48 using confirmatory factor analysis. Correlations between self-report questions and drug concentrations were estimated with Pearson's correlations for continuous outcomes and point-biserial correlations for dichotomous outcomes. Receiver operating characteristic (ROC) analyses were conducted to assess the performance of self-report measures in predicting protective or perfect TFV-DP concentrations. Of the 369 participants who completed week 12 or 48 visits, the mean age was 35 (standard deviation 9 years), with 79% White, 12% Black, and 29% Hispanic. Correlations between self-report measures of adherence (both individual items and the adherence factor) and quantifiable FTC-TP and continuous TFV-DP concentrations showed that all self-report measures were significantly associated with these objective measures. Compared to a summary measure of self-reported adherence, the 4-week percent taken question medication recall was the only self-report item similarly or more strongly associated with recent adherence and long-term protective and perfect adherence at weeks 12 and 48. ROC analysis also showed that 4-week percent taken question had a reasonable AUC (0.798 at week 12 and 0.758 at week 48) in predicting protective TFV-DP concentrations. All single-item self-report questions assessing PrEP adherence were significantly associated with biomarker quantification, with the 4-week percent taken question performing best. Therefore, in the absence of drug concentration measurements, a 4-week self-report percent taken question may be a good single-item measure of PrEP adherence.
| S-EPMC6624646 | biostudies-literature
Project description:From a healthcare perspective, infection due to the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and the ensuing syndrome called COVID-19 (coronavirus disease 2019) represents the biggest challenge the world has faced in several decades. Particularly worrisome are the high contagiousness of the virus and the saturation of hospitals' capacity due to overwhelming caseloads. Non-pharmaceutical interventions such as quarantine and inter-personal distancing are crucial to limiting the spread of the virus in the general population, but more tailored interventions may be needed at an individual level on a case-by-case basis. In this perspective, the most insidious situation is when an individual has contact with a contagious subject without adequate protection. If rapidly recognized afterwards, this occurrence may be promptly addressed through a post-exposure chemoprophylaxis (PEP) with antiviral drugs. This strategy has been implemented for other respiratory viruses (influenza above all) and was successfully used in South Korea among healthcare workers against the Middle East respiratory syndrome (MERS) coronavirus, by providing people who were exposed to high-risk contacts with lopinavir-ritonavir plus ribavirin. Initial experiences with the use of hydroxychloroquine to prevent COVID-19 also seem promising. Post-exposure chemoprophylaxis might help mitigate the spread of SARS-CoV-2 in the current phase of the COVID-19 pandemic.
| S-EPMC7312384 | biostudies-literature