New 'mini-pillbox' device could deliver three HIV drugs in a single once-weekly dose

A new oral device that is taken once a week in a capsule could deliver two or three antiretroviral drugs and significantly reduce the risk of missing does or of developing drug resistance, according to research published today in Nature Communications.

The investigators describe their device as a 'mini-pillbox' – no larger than a normal pill capsule but containing a star-shaped structure that can dispense drugs for up to seven days. The star shape prevents the tiny device from passing out of the stomach into the small intestine until the drugs have been dispensed, at which point the device breaks up and passes into the intestines. The tiny device does not prevent food from passing through the digestive system.

The mini-pillbox can deliver up to six formulations (one per arm) but can only be used for once-weekly dosing when the daily dose is 50mg or less. The investigators used the integrase inhibitors dolutegravir and cabotegravir and the non-nucleoside reverse transcriptase inhibitor rilpivirine to test the device in pigs. The drugs were loaded onto polymer matrices which released the drugs slowly over the course of a week.



In pharmacology, a medication which maintains its effects over a long period of time, such as an injection or implant.

pilot study

Small-scale, preliminary study, conducted to evaluate feasibility, time, cost, adverse events, and improve upon the design of a future full-scale research project.



The physical form in which a drug is manufactured or administered. Examples of formulations include tablets, capsules, powders, and oral and injectable solutions. A drug may be available in multiple formulations.


Beneath or introduced beneath the skin, e.g. a subcutaneous injection is an injection beneath the skin.



Refers to the mouth, for example a medicine taken by mouth.

The pilot study showed that concentrations of each drug remained high, and in the case of rilpivirine at levels matching the peak seen with daily dosing, for at least one week. The speed at which the drugs were released could be altered by using a different polymer to hold the drug in place.

One drawback is that the delivery method is only suitable for drugs that are stable in stomach acid. Use of tenofovir alafenamide (TAF) had to be abandoned because only ten per cent of the drug remained in a stable form that could be metabolised after ten hours’ exposure to stomach acid.

The device is designed to overcome difficulties in dosing slow-release formulations orally. For people who do not want to receive a long-acting formulation by intramuscular injection, a once-weekly pill could be very attractive.

ViiV Healthcare is developing the combination of cabotegravir and rilpivirine as a long-acting formulation to be dosed every two months by subcutaneous injection.

The device would also be suitable for delivering drugs for pre-exposure prophylaxis (PrEP), say the study investigators. They modelled the potential impact of the mini-pillbox when used to deliver PrEP. Assuming a similar level of efficacy for the drugs used in the device as for tenofovir, they estimated that weekly PrEP would improve the efficacy of PrEP by 20% compared to daily PrEP, due to improved adherence.

The research was part-funded by the Bill and Melinda Gates Foundation and the United States National Institutes of Health.


Kirtane A et al. Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy. Nature Communications 9(2) 1-12, 2018.