Long-Acting Formulations (Monthly Injections): Rilpivirine-LA, Raltegravir, Patient Views
The development of a nanosuspension formulation of the NNRTI rilpivirine that could be given by intramuscular injection was reported several years ago. A single-dose pharmacokinetic study in HIV negative people reported prolonged exposure in plasma, genital compartments and rectal following single 300, 600, or 1200 mg doses,13 together with a study reporting a lack of negative drug interactions between rilpivirine and dolutegravir (both also presented this year at CROI).14
While this was presented for its potential to reducing the reliance on daily adherence in the context of PrEP, this might have important options for HIV treatment. This would require other ARVs with a similar formulation to construct a combination. The development of a similar formulation for dolutegravir is clearly of interest.15
A safety issue for long-acting formulations, especially in the absence of an antidote to rapidly eliminate the active compound in the event of a severe adverse reaction, might be covered by a period of oral dosing to confirm individual tolerability, especially as both integrase and NNRTI classes have been associated with hypersensitivity reactions.
A recent survey of 400 HIV positive patients attending two US clinics reported 61%, 72% and 84% interest in ART injections based on weekly, two-weekly and monthly formulation respectively, with higher interest in people with concerns about adherence, although 35% were also concerned about needle use.16
Unless stated otherwise, references are to the Programme and Abstracts of the 13th International Workshop on Clinical Pharmacology of HIV Therapy, 16-18 April 2012, Barcelona. These are published in Reviews in Antiviral Therapy & Infectious Diseases, Volume 3: 2012 and available free in PDF format online.
- Ramanathan S et al. Pharmacokinetics and drug interaction profile of cobicistat boosted‐EVG with atazanavir, rosuvastatin or rifabutin. 13th PK Workshop, Barcelona, 2012. Oral abstract O_03.
- Ramanathan S et al. Safety/tolerability, pharmacokinetics, and boosting of twice-daily cobicistat administered alone or in combination with darunavir or tipranavir. 13th PK Workshop, Barcelona, 2012. Poster P_08.
- Kaduda T et al. Bioavailability of two FDC formulations of darunavir/cobicistat 800/150mg compared with darunavir/ritonavir 800/100mg co-administered as single agents. 13th PK Workshop, Barcelona, 2012. Oral abstract O_20.
- Ramanathan S et al. Pharmacokinetics of a novel EVG/COBI/FTC/GS-7340 single tablet regimen. 13th PK Workshop, Barcelona, 2012. Abstract O_13.
- Safety and efficacy of elvitegravir/cobicistat/emtricitabine/GS-7340 single tablet regimen versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single tablet regimen in HIV 1 infected, antiretroviral treatment-naive adults.
- Safety and efficacy of darunavir/cobicistat/emtricitabine/GS-7340 single tablet regimen versus cobicistat-boosted darunavir plus emtricitabine/tenofovir disoproxil fumarate fixed dose combination in HIV-1 infected, antiretroviral treatment naive adults.
- Song I et al. Metabolism and drug-drug interaction profile of dolutegravir (DTG, S/GSK1349572). 13th PK Workshop, Barcelona, 2012. Abstract O_17.
- Ford SL et al. Etravirine has no effect on the pharmacokinetics of S/GSK1265744, a novel HIV Integrase inhibitor. 13th PK Workshop, Barcelona, 2012. Poster abstract P_15.
- A single dose escalation study to investigate the safety, tolerability and pharmacokinetics of intramuscular and subcutaneous long acting GSK1265744 in healthy subjects.
- A study to investigate the safety, tolerability and pharmacokinetics of repeat dose administration of long-acting GSK1265744 and long-acting TMC278 intramuscular and subcutaneous injections in healthy adult subjects.
- Hwang C et a. Antiviral activity, exposure- response, and resistance analyses of monotherapy with the novel HIV NRTI BMS- 986001 in ART-experienced subjects. 13th PK Workshop, Barcelona, 2012. Oral abstract O_06.
- Cotte et al. A phase-Ib/IIa dose-escalation study of OBP-601 (4'-ethynyl-d4T, festinavir) in treatment-experienced, HIV-1- infected patients. 50th ICAAC, 12-15 September 2010, Boston. Abstract H-933.
- Else L et al. Pharmacokinetics of long-acting rilpivirine in plasma, genital tract and rectum of HIV negative females and males administered a single 600 mg dose. 13th PK Workshop, Barcelona, 2012. Oral abstract O_12.
- Jackson A et al. Rilpavirine-LA formulation: pharmacokinetics in plasma, genital tract in HIV negative females and rectum in males. 19th Conference of Retroviruses and Opportunistic Infections, 5-8 March 2012, Seattle. Oral abstract 35.
- Crauwels H et al. Absence of pharmacokinetic interaction between the NNRTI rilpivirine (TMC278) and the integrase inhibitor raltegravir. 19th Conference of Retroviruses and Opportunistic Infections, 5-8 March 2012, Seattle. Poster abstract 617.
- Swindells S et al. Long-acting parenteral nanoformulated antiretroviral therapy: patient interest and attitudes. 13th PK Workshop, Barcelona, 2012. Poster abstract P_01.
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