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. 2013 Nov;8(6):565-71.
doi: 10.1097/COH.0000000000000002.

Long-acting Injectable Antiretrovirals for HIV Treatment and Prevention

Free PMC article

Long-acting Injectable Antiretrovirals for HIV Treatment and Prevention

William R Spreen et al. Curr Opin HIV AIDS. .
Free PMC article


Purpose of review: Long-acting antiretroviral (ARV) drugs may improve adherence to therapy and extend opportunities for therapeutic or prophylactic intervention to underserved patient populations. This review focuses on recent advances in the development of small molecule long-acting injectable ARV agents.

Recent findings: The need for combination ART and physicochemical and dosing limitations of current ARV drugs impede attempts to redevelop them as long-acting injectable formulations. However, the intrinsic properties of rilpivirine, a nonnucleoside reverse transcriptase inhibitor, and GSK1265744, an HIV-1 integrase strand transfer inhibitor, have enabled crystalline nanoparticle formulations to progress to clinical trials.

Summary: Investigational long-acting injectable nanoformulations of rilpivirine and GSK1265744 are clinical-stage development candidates. Complementary pharmacologic properties of both agents - different mechanisms of action, resistance profiles, metabolic pathways, lack of drug interactions and low daily oral doses - offer the potential for combination use. Phase I studies of the pharmacokinetics and safety of each long-acting formulation alone and in combination indicate that a monthly dosing regimen is possible for HIV treatment. An ongoing phase IIb trial of oral GSK1265744 and oral rilpivirine is evaluating this two-drug regimen for maintenance of virologic suppression; results will inform future studies using the injectable formulations. Additional preclinical and clinical studies indicate a potential use of each agent for HIV pre-exposure prophylaxis.


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Mean plasma levels of GSK1265744 over time following single-dose administration of long-acting formulation . GSK1265744 (200 mg/ml) was administered as a single IM (gluteal) or SC (abdominal) injection or equally divided IM or SC injection. Each cohort comprised eight healthy adult patients (six active/two placebo). The dashed line represents the plasma PA-IC90 value for GSK1265744 against wild-type HIV-1 of 0.166 μg/ml.

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