Post-exposure prophylaxis to prevent HIV: new drugs, new approaches, and more questions.
Ontology highlight
ABSTRACT:
SUBMITTER: Mayer KH
PROVIDER: S-EPMC11331403 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
Publications
Post-exposure prophylaxis to prevent HIV: new drugs, new approaches, and more questions.
Mayer Kenneth H KH Allan-Blitz Lao-Tzu LT
The lancet. HIV 20231109 12
Post-exposure prophylaxis (PEP) to prevent HIV acquisition has been recommended for over three decades, but remains underutilised. Over the past decade, clinical trials have established the safety and tolerability of newer PEP regimens, particularly those containing integrase strand transfer inhibitors (INSTIs) combined with a tenofovir and lamivudine or emtricitabine backbone. Several of these regimens were better tolerated than historical controls. Studies in macaques found that shorter course ...[more]
Similar Datasets
Project description:There are 34 million people living with human immunodeficiency virus (HIV) worldwide and each year this number increases. Until a vaccine is discovered, the prevention of new HIV infections remains an urgent priority. Several trials studying the use of oral and topical agents for the prevention of HIV infection have already been completed. Adherence has proved to be a major challenge in achieving product efficacy.To provide the clinical pharmacist with an understanding of the oral pre-exposure prophylaxis (PrEP) and topical microbicide product pipeline whilst emphasizing the critical importance of adherence to these drugs to avert HIV infection.PubMed/Medline and the web-based clinical trials registry (ClinTrials.gov) were searched using appropriate key words. For the time period 1992-2013--all phase II and phase III safety and effectiveness studies--testing agents for prevention of HIV infection were included in the review. Efficacy estimates, adherence estimates and reported challenges with adherence were extracted.Twenty-four phase II and III clinical trials were found during review. Of these, 20 trials have been completed, and six trials show effectiveness in preventing HIV infection. The majority of the successful trials were to oral PrEP and to date only one microbicide trial of a vaginal antiretroviral microbicide gel has showed effectiveness. Adherence to study product played a major role in trial outcomes and there are several reasons for non-adherence. These include high on-trial pregnancy rates, low trial retention rates, low participant perception of risk, participant characteristics such as age <25 years, single status, migratory partners and trial fatigue. Study product characteristics such as dosage form, dosing interval, as well as associated adverse events may also influence adherence.Moderate to high adherence is critical to demonstrate efficacy of drugs for HIV prevention. For topical agents, intermittent use associated with coitus is more effective than daily use, particularly if sex is infrequent or partners migrant. For oral agents, daily use is effective but the motivation to use the drug and high risk perception is important. In serodiscordant couples, early initiation of highly active antiretroviral therapy in the infected partner affords almost complete protection to the negative partner. Drugs need to be tailored to the population at risk and availability of multiple drug options are important.
| S-EPMC3947256 | biostudies-other
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:HIV infection in HCW is an occupational hazard requiring policy decisions by the health care administrators. In this article we have outlined a post exposure prophylaxis protocol following HIV exposure in HCWs. By determining the HIV status code of the source and the HIV exposure code of the HCWs, recommendations for PEP are forwarded. Occupational exposures should be considered urgent medical and surgical concerns to ensure timely administration of PEP. At the end, an algorithm is provided to guide exposed health-care workers in deciding when to consider PEP.
| S-EPMC5532134 | biostudies-other
Project description:There are currently several ongoing or planned trials evaluating the efficacy of pre-exposure prophylaxis (PrEP) as a preventative approach to reducing the transmission of HIV. PrEP may prove ineffective, demonstrate partial efficacy, or show high efficacy and have the potential to reduce HIV infection in a significant way. However, in addition to the trial results, it is important that issues related to delivery, implementation and further research are also discussed. As a part of the ongoing discussion, in June 2009, the Bill & Melinda Gates Foundation sponsored a Planning for PrEP conference with stakeholders to review expected trial results, outline responsible educational approaches, and develop potential delivery and implementation strategies. The conference reinforced the need for continued and sustained dialogue to identify where PrEP implementation may fit best within an integrated HIV prevention package. This paper identifies the key action points that emerged from the Planning for PrEP meeting.
| S-EPMC2914050 | biostudies-literature
Project description:ObjectivesSexual assault (SA) is recognized as a public health problem of epidemic proportions. Guidelines recommend the administration of post-exposure prophylaxis (PEP) after an SA. However, few data are available about the feasibility of this strategy, and this study was conducted to assess this.MethodsWe conducted a retrospective, longitudinal, observational study in SA victims attending the Hospital Clinic in Barcelona from 2006 to 2015. A total of 1695 SA victims attended the emergency room (ER), of whom 883 met the PEP criteria. Five follow-up visits were scheduled at days 1, 10, 28, 90 and 180 in the out-patient clinic. The primary endpoint was PEP completion rate at day 28. Secondary endpoints were loss to follow-up, treatment discontinuation, occurrence of adverse events (AEs) and rate of seroconversion.ResultsThe median age of participants was 25 years [interquartile range (IQR) 21-33 years] and 93% were female. The median interval between exposure and presentation at the ER was 13 h (IQR 6-24 h). The level of risk was appreciable in 47% (n = 466) of individuals. Of 883 patients receiving PEP, 631 lived in Catalonia. In this group, the PEP completion rate at day 28 was 29% (n = 183). The follow-up rate was 63% (n = 400) and 38% (n = 241) at days 1 and 28, respectively. Treatment discontinuation was present in 58 (15%) of 400 patients who attended at least the day 1 visit, the main reason being AEs (n = 35; 60%). AEs were reported in 226 (56%) patients, and were mainly gastrointestinal (n = 196; 49%). Only 211 (33%) patients returned for HIV testing at day 90. A single seroconversion was observed in a men who have sex with men (MSM) patient at day 120.ConclusionsFollow-up and compliance rates in SA victims were poor. In addition, > 50% of the patients experienced AEs, which were the main reason for PEP interruption. Strategies to increase follow-up testing and new better tolerated drug regimens must be investigated to address these issues.
| S-EPMC6916272 | 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:Recent studies have highlighted the efficacy of and willingness to use pre-exposure prophylaxis (PrEP) to prevent HIV infection among people who inject drugs (PWID), however knowledge of real-world applicability is limited. We aimed to quantify the real-world eligibility for HIV-PrEP among HIV-negative PWID in Montreal, Canada (n = 718). Eligibility was calculated according to US Centers for Disease Control and Prevention (CDC) guidelines and compared to risk of HIV acquisition according to the assessing the risk of contracting HIV (ARCH-IDU) risk screening tool. Over one-third of participants (37%) were eligible for HIV PrEP, with 1/3 of these eligible due to sexual risk alone. Half of participants were considered high risk of HIV acquisition according to ARCH-IDU, but there was poor agreement between the two measures. Although a large proportion of PWID were eligible for HIV-PrEP, better tools that are context- and location-informed are needed to identify PWID at higher risk of HIV acquisition.
| S-EPMC10710293 | biostudies-literature
Project description:Background: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive. The evaluation of HIV consequences without treatment interference has been performed in naïve (non-treated) patients, but assessment of treatment toxicity without viral interference is usually restricted to in vitro assays. Objective: The objective of the present study is to determine whether antiretroviral treatment without HIV interference can lead to mtDNA disturbances. We studied clinical, mitochondrial, and metabolic toxicity in non-infected healthy patients who received HIV post-exposure prophylaxis (PEP) to prevent further infection. We assessed two different PEP regimens according to their composition to ascertain if they were the cause of tolerability issues and derived toxicity. Methods: We analyzed reasons for PEP discontinuation and main secondary effects of treatment withdrawal, mtDNA content from peripheral blood mononuclear cells and metabolic profile, before and after 28 days of PEP, in 23 patients classified depending on PEP composition: one protease inhibitor (PI) plus Zidovudine/Lamivudine (PI plus AZT + 3TC; n = 9) or PI plus Tenofovir/Emtricitabine (PI plus TDF + FTC; n = 14). Results: Zidovudine-containing-regimens showed an increased risk for drug discontinuation (RR = 9.33; 95% CI = 1.34-65.23) due to adverse effects of medication related to gastrointestinal complications. In the absence of metabolic disturbances, 4-week PEP containing PI plus AZT + 3TC led to higher mitochondrial toxicity (-17.9 ± 25.8 decrease in mtDNA/nDNA levels) than PI plus TDF + FTC (which increased by 43.2 ± 24.3 units mtDNA/nDNA; p < 0.05 between groups). MtDNA changes showed a significant and negative correlation with baseline alanine transaminase levels (p < 0.05), suggesting that a proper hepatic function may protect from antiretroviral toxicity. Conclusions: In absence of HIV infection, preventive short antiretroviral treatment can cause secondary effects responsible for treatment discontinuation and subclinical mitochondrial damage, especially pyrimidine analogs such as AZT, which still rank as the alternative option and first choice in certain cohorts for PEP. Forthcoming efforts should be focused on launching new strategies with safer clinical and mitotoxic profile.
| S-EPMC7264262 | biostudies-literature
Project description:AimsTo improve the care of children who are victims of child sexual abuse (CSA) by routinely assessing eligibility for HIV post-exposure prophylaxis (PEP) and to investigate the feasibility, safety, and efficacy of such treatment started in a paediatric emergency department in Malawi.MethodsChildren presenting to the Queen Elizabeth Central Hospital, Blantyre between 1 January 2004 and 31 December 2004 with a history of alleged CSA were assessed for eligibility for HIV PEP and followed prospectively for six months.ResultsA total of 64 children presented with a history of alleged CSA in the 12 month period; 17 were offered PEP. The remainder were not offered PEP because of absence of physical signs of abuse (n = 20), delay in presentation beyond 72 hours from assault (n = 11), repeated sexual abuse in the preceding six months (n = 15), and HIV infection found on initial testing (n = 1). No family refused an HIV test. No side effects due to antiretroviral therapy were reported. Of the 17 children commenced on PEP, 11 returned for review after one month, seven returned at three months, and two of 15 returned at six months post-assault. None have seroconverted.ConclusionsIn a resource-poor setting with a high HIV prevalence, HIV PEP following CSA is acceptable, safe, and feasible. HIV PEP should be incorporated in to national guidelines in countries with a high community prevalence of HIV infection.
| S-EPMC1720206 | biostudies-literature
Project description: Not available
| S-EPMC4203625 | biostudies-literature