A new, long-acting antiretroviral injection might be an effective alternative to daily oral doses of the same medication in the case of HIV, a new clinical trial suggests.
Antiretroviral (ARV) drugs are administered to diminish the load of HIV in the system, slowing the disease and preventing transmission. According to the Centers for Disease Control and Prevention (CDC), it is thanks to ARV drugs that the number of deaths occurring as a result of AIDS – which is caused by HIV – has been steadily on the decline in recent years.
However, the treatment with ARV drugs is intense: patients must take a combination of medicines every day, even after the viral load becomes undetectable in the bloodstream, in order to ensure that the virus does not regain momentum.
A team of researchers from a series of institutions, led by Dr. David A. Margolis, is now testing a long-acting ARV injection that would be able to act as a replacement for daily oral medication.
“Adherence to medication remains an important challenge in HIV treatment. Long-acting injectable ART could provide some patients with a more convenient approach to manage HIV infection that avoids daily oral dosing, and the need to keep, store, and transport medications as they go about their daily lives,” says Dr. Margolis.
The clinical trial has just completed phase II, and the results are published in The Lancet. They were also presented yesterday at the ninth International AIDS Society conference, held in Paris, France.
The study devised an ARV injection containing two drugs that have been used in HIV treatments under the form of oral medication: cabotegravir and rilpivirine. Researchers have so far found that this injectable treatment appears to be as effective as the normal, daily administration of the same drugs in the form of oral medicine.
Dr. Margolis and his colleagues first conducted an induction stage, wherein they looked out for adverse events to the two drugs. This initial stage was performed with the help of 309 participants.
These patients were administered oral doses of cabotegravir (30 milligrams) and abacavir-lamivudine (600 milligrams to 300 milligrams) every day, for a period of 20 weeks. Of these patients, 286 participants did not experience any significant averse events. These people went ahead with the trial.
In the next stage, which is called the “maintenance phase,” the patients were randomly split into three groups. One hundred and fifteen participants were administered injections of cabotegravir and rilpivirine once every 4 weeks, 115 participants received the same treatment every 8 weeks, and 56 participants were set to continue the oral cabotegravir and abacavir-lamivudine treatment as before. The maintenance therapy went on for a total of 96 weeks.
After 32 weeks, it was found that 94 percent of the patients in the first group, 95 percent in the second group, and 91 percent in the third group had maintained viral suppression.
At the end of the 96-week period, 87 percent of the participants in the first group, 94 percent of those in the second group, and 84 percent of those in the third had maintained viral suppression.
In short, the cabotegravir and rilpivirine injection appeared to be at least as effective as a regular treatment with oral doses.
Some adverse events were also noted, with the most frequent being pain where the intramuscular injection had been administered. This was reported by 97 percent of the participants in the first group, and by 96 percent of those in the second group. In most cases, however, this reaction lasted only 3 days, and the pain was mild.
Only 4 percent of the total number of participants were forced to withdraw from the trial due to adverse events. Of these, two came from the first group, eight from the second group, and one from the third group.
The study spanned 50 locations across five different countries, including Canada, France, Germany, Spain, and the United States. Despite this, 91 percent of the participants were male.
Another noteworthy limitation was that patients were only considered eligible to take part in the trial if they had at least 200 (but no more than 350) blood cells per cubic millimeter of blood. This, the researchers acknowledge, is not representative of the diversity of HIV patients.
In a commentary published alongside the main article, Prof. Mark A. Boyd, from the University of Adelaide in Australia, and Prof. David A. Cooper, from the Kirby Institute of the University of New South Wales, also in Australia, note that not all HIV patients may find an injection more convenient than orally administered drugs.
“[At least in Australia] people living with HIV can be dispensed anywhere from 2 to 6 months’ supply of ART [antiretroviral therapy] at a time. This scenario, compared with having to seek healthcare to be injected on a monthly basis, might make the injectable option seem less convenient than conventional oral therapy for some people,” they say.
Finally, it should be noted that the main article includes an acknowledgment that some of the researchers involved in this study are currently employed by, and stakeholders in, a well-known pharmaceutical company.