Dataset Information

Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings.

ABSTRACT: The vast majority of people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome reside in the developing world, in settings characterized by limited health budgets, critical shortages of doctors, limited laboratory monitoring, a substantial burden of HIV in children, and high rates of coinfection, in particular tuberculosis. Therefore, the extent to which new antiretrovirals will contribute to improvements in the management of HIV globally will depend to a large extent on their affordability, ease of use, low toxicity profile, availability as pediatric formulations, and compatibility with tuberculosis and other common drugs. We undertook a systematic review of the available evidence regarding drug interactions, and the efficacy and safety of rilpivirine (also known as TMC-278), and assessed our findings in view of the needs and constraints of resource-limited settings. The main pharmacokinetic interactions relevant to HIV management reported to date include reduced bioavailability of rilpivirine when coadministered with rifampicin, rifabutin or acid suppressing agents, and reduced bioavailability of ketoconazole. Potential recommendations for dose adjustment to compensate for these interactions have not been elaborated. Trials comparing rilpivirine and efavirenz found similar outcomes up to 96 weeks in intent-to-treat analysis; failure of rilpivirine was mainly virological, whereas failure among those exposed to efavirenz was mainly related to the occurrence of adverse events. Around half of the patients who fail rilpivirine develop non-nucleoside reverse transcriptase inhibitor resistance mutations. The incidence of Grade 2-4 events was lower for rilpivirine compared with efavirenz. Grade 3-4 adverse events potentially related to the drugs were infrequent and statistically similar for both drugs. No dose-response relationship was observed for efficacy or safety, and the lowest dose (25 mg) was selected for further clinical development. The potential low cost and dose of the active pharmaceutical ingredient means that rilpivirine can potentially be manufactured at a low price. Moreover, its long half-life suggests the potential for monthly dosing via nonoral routes, with promising early results from studies of a long-acting injectable formulation. These characteristics make rilpivirine an attractive drug for resource-limited settings. Future research should assess the potential to improve robustness and assess the clinical significance of interaction with antituberculosis drugs.

SUBMITTER: Ford N

PROVIDER: S-EPMC3218710 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings.

Ford Nathan N Lee Janice J Andrieux-Meyer Isabelle I Calmy Alexandra A

HIV/AIDS (Auckland, N.Z.) 20110428

The vast majority of people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome reside in the developing world, in settings characterized by limited health budgets, critical shortages of doctors, limited laboratory monitoring, a substantial burden of HIV in children, and high rates of coinfection, in particular tuberculosis. Therefore, the extent to which new antiretrovirals will contribute to improvements in the management of HIV globally will depend to a large ex ...[more]

PMID: 22096405

Similar Datasets

Project description:Background: Telemedicine, or healthcare delivery from a distance, has evolved over the past 50 years and helped alter health care delivery to patients around the globe. Its integration into numerous domains has permitted high quality care that transcends obstacles of geographic distance, lack of access to health care providers, and cost. Ultrasound is an effective diagnostic tool and its application within telemedicine ("tele-ultrasound") has advanced substantially in recent years, particularly in high-income settings. However, the utility of tele-ultrasound in resource-limited settings is less firmly established. Objective: To determine whether remote tele-ultrasound is a feasible, accurate, and care-altering imaging tool in resource-limited settings. Data Sources: PubMed, MEDLINE, and Embase. Study Eligibility Criteria: Twelve original articles met the following eligibility criteria: full manuscript available, written in English, including a direct patient-care intervention, performed in a resource-limited setting, images sent to a remote expert reader for interpretation and feedback, contained objective data on the impact of tele-ultrasound. Study Appraisal and Synthesis Methods: Abstracts were independently screened by two authors against inclusion criteria for full-text review. Any discrepancies were settled by a senior author. Data was extracted from each study using a modified Cochrane Consumers and Communication Review Group's data extraction template. Study bias was evaluated using the ROBINS-I tool. Results: The study results reflect the diverse applications of tele-ultrasound in low-resource settings. Africa was the most common study location. The specialties of cardiology and obstetrics comprised most studies. Two studies primarily relied on smartphones for image recording and transmission. Real-time, rather than asynchronous, tele-ultrasound image interpretation occurred in five of the 12 studies. The most common outcome measures were image quality, telemedicine system requirements, diagnostic accuracy, and changes in clinical management. Limitations: The studies included were of poor quality with a dearth of randomized control trials and with significant between study heterogeneity which resulted in incomplete data and made cross study comparison difficult. Conclusions and Implications of Key Findings: Low-quality evidence suggests that ultrasound images acquired in resource-limited settings and transmitted using a telemedical platform to an expert interpreter are of satisfactory quality and value for clinical diagnosis and management.

Project description:BackgroundCryptococcosis is an opportunistic fungal infection that primarily affects people with advanced HIV/AIDS and is an important cause of morbidity and mortality around the globe. By far the most common presentation of the disease is cryptococcal meningitis (CM), which leads to an estimated 15-20% of all HIV related deaths worldwide, 75% of which are in sub-Saharan Africa. However, to the best of our knowledge there is quite limited reviewed data on the epidemiology of cryptococcal antigenemia in a large HIV-infected population in resource limited settings.MethodsArticles published in English irrespective of the time of publication were systematically searched using comprehensive search strings from PubMed/Medline and SCOPUS. In addition, Google Scholar and Google databases were searched manually for grey literature. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. The pooled prevalence of cryptococcal antigenemia was determined with 95% confidence interval (CI).ResultsAmong 2941 potential citations, we have included 22 studies with a total of 8338 HIV positive individuals. The studies were reported in ten different countries during the year (2007-2018). Most of the articles reported the mean CD4 count of the participants below 100 cells/?l. The pooled prevalence of cryptococcal antigenemia at different CD4 count and ART status was at 8% (95%CI: 6-10%) (ranged between 1.7 and 33%). Body mass index (BMI) <?18.5?kg/m2, CD4 count <?100 cells, patients presenting with headache and male gender were reported by two or more articles as an important predictors of cryptococcal antigenemia.ConclusionsImplementing a targeted screening of HIV patients with low BMI, CD4 count <?100 cells, having headache and males; and treatment for asymptomatic cryptococcal disease should be considered. Additional data is needed to better define the epidemiology of cryptococcal antigenemia and its predictors in resource limited settings in order to optimize the prevention, diagnosis, and treatment strategies.

Dataset Information

Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings.

Publications

Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets