Long-Acting Anti-HIV Drugs Targeting HIV-1 Reverse Transcriptase and Integrase.
HIV-1
antivirals
integrase
long-acting formulation
reverse transcriptase
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
20 Apr 2019
20 Apr 2019
Historique:
received:
17
03
2019
revised:
16
04
2019
accepted:
18
04
2019
entrez:
24
4
2019
pubmed:
24
4
2019
medline:
24
4
2019
Statut:
epublish
Résumé
One of the major factors contributing to HIV-1 drug resistance is suboptimal adherence to combination antiretroviral therapy (cART). Currently, recommended cART for HIV-1 treatment is a three-drug combination, whereas the pre-exposure prophylaxis (PrEP) regimens consist of one or two antivirals. Treatment regimens require adherence to a once or twice (in a subset of patients) daily dose. Long-acting formulations such as injections administered monthly could improve adherence and convenience, and thereby have potential to enhance the chances of expected outcomes, although long-lasting drug concentrations can also contribute to clinical issues like adverse events and development of drug resistance. Globally, two long-acting antivirals have been approved, and fifteen are in clinical trials. More than half of investigational long-acting antivirals target HIV-1 reverse transcriptase (HIV-1 RT) and/or integrase (HIV-1 IN). Here, we discuss the status and potential of long-acting inhibitors, including rilpivirine (RPV), dapivirine (DPV), and 4-ethynyl-2-fluoro-2-deoxyadenosine (EFdA; also known as MK-8591), which target RT, and cabotegravir (CAB), which targets IN. The outcomes of various clinical trials appear quite satisfactory, and the future of long-acting HIV-1 regimens appears bright.
Identifiants
pubmed: 31010004
pii: ph12020062
doi: 10.3390/ph12020062
pmc: PMC6631967
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : NIAID NIH HHS
ID : P30 AI050409
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM118012
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI076119
Pays : United States
Organisme : NIH HHS
ID : GM118012 and AI076119
Pays : United States
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