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

Hdl Handle:
http://hdl.handle.net/10144/220333
Title:
Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings.
Authors:
Ford, Nathan; Lee, Janice; Andrieux-Meyer, Isabelle; Calmy, Alexandra
Journal:
HIV/AIDS - Research and Palliative Care
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.
Affiliation:
Médecins Sans Frontières, Geneva, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa; Service of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland
Publisher:
DovePress
Issue Date:
28-Apr-2011
URI:
http://hdl.handle.net/10144/220333
DOI:
10.2147/HIV.S14559
PubMed ID:
22096405
Additional Links:
http://www.dovepress.com/safety-efficacy-and-pharmacokinetics-of-rilpivirine-systematic-review--peer-reviewed-article-HIV
Type:
Article
Language:
en
ISSN:
1179-1373
Appears in Collections:
HIV/AIDS

Full metadata record

DC FieldValue Language
dc.contributor.authorFord, Nathanen
dc.contributor.authorLee, Janiceen
dc.contributor.authorAndrieux-Meyer, Isabelleen
dc.contributor.authorCalmy, Alexandraen
dc.date.accessioned2012-04-24T16:32:31Z-
dc.date.available2012-04-24T16:32:31Z-
dc.date.issued2011-04-28-
dc.identifier.citationHIV AIDS Res Palliat Care 2012; 11(3):35-44en
dc.identifier.issn1179-1373-
dc.identifier.pmid22096405-
dc.identifier.doi10.2147/HIV.S14559-
dc.identifier.urihttp://hdl.handle.net/10144/220333-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.publisherDovePressen
dc.relation.urlhttp://www.dovepress.com/safety-efficacy-and-pharmacokinetics-of-rilpivirine-systematic-review--peer-reviewed-article-HIVen
dc.rightsArchived with thanks to HIV/AIDS (Auckland, N.Z.)en
dc.subject.meshHIVen
dc.subject.meshAntiretroviral Therapyen
dc.subject.meshpharmacokineticsen
dc.titleSafety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings.en
dc.typeArticleen
dc.contributor.departmentMédecins Sans Frontières, Geneva, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa; Service of Infectious Diseases, Geneva University Hospital, Geneva, Switzerlanden
dc.identifier.journalHIV/AIDS - Research and Palliative Careen

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