Two injectable antiretrovirals, cabotegravir and rilpivirine, taken every four or eight weeks maintained HIV suppression over the long term, according to a presentation at the 9th International AIDS Society Conference on HIV Science (IAS 2017) taking place this week in Paris.
About 90 percent of participants in the LATTE-2 trial who switched to the injectable drugs still had an undetectable viral load at 96 weeks, Joseph Eron, MD, of the University of North Carolina, Chapel Hill reported.
Modern antiretroviral therapy is highly effective if taken as directed every day, but maintaining good adherence over the long term can be challenging. Long-acting injectable drugs could offer an alternative for people facing a lifetime of treatment.
Eron presented results from a clinical trial evaluating a two-drug maintenance regimen consisting of long-acting formulations of ViiV Healthcare’s experimental integrase inhibitor cabotegravir and Janssen’s NNRTI rilpivirine, which is currently approved in the oral formulation Edurant and in the Complera combination pill.
To ensure the safety and tolerability of this dual combination before testing the injectable formulations, the earlier LATTE-1 trial evaluated oral cabotegravir plus Edurant as a simplified maintenance regimen for people who achieved an undetectable viral load using standard three-drug antiretroviral therapy.
Good results from that study laid the groundwork for the Phase IIb LATTE-2 trial, which tested long-acting nanosuspension formulations of cabotegravir and rilpivirine given as intramuscular injections. (Nanosuspension means small particles of the drug are delivered in a solution of water to facilitate absorption.) The shots are given in the buttocks and currently must be administered by a health care provider, but self-injection may be possible in the future, Eron said.
This open-label study enrolled 309 participants in North America and Europe who were being treated for HIV for the first time. About 9 percent were women, more than 80 percent were white and the median age was 35 years. The median baseline CD4 count was approximately 500 cells/cubic milliliter and nearly a fifth had a high baseline viral load.
Participants initially started a three-drug induction regimen of oral cabotegravir plus Epzicom (abacavir/lamivudine). After 20 weeks, those with a viral load below 50 copies/milliliter were randomly assigned either to stay on the same oral regimen or switch to long-acting cabotegravir and rilpivirine injections. The 286 people who met this criterion received either 400 milligrams of cabotegravir plus 600 mg rilpivirine administered every four weeks (Q4W) or 600 mg cabotegravir plus 900 mg rilpivirine given every eight weeks (Q8W).
In 2016, Margolis presented 32-week results from LATTE-2, showing that 95 percent of participants who switched to the Q8W injectable combo and 94 percent of those on the Q4W regimen maintained an undetectable viral load, as did 91 percent of those who stayed on the oral regimen.
After two years of treatment, most participants continued to maintain viral suppression, Eron reported at the IAS meeting. At 96 weeks, 94 percent of people on the Q8W injectable regimen and 87 percent of those on the Q4W regimen still had undetectable HIV RNA, compared with 84 percent of those who continued on the oral regimen.
Three people who received injectable cabotegravir and rilpivirine experienced virological failure, two on the Q8W regimen and one on the oral regimen. No one receiving the Q4W regimen experienced treatment failure, Eron said.
Injectable cabotegravir and rilpivirine were safe and generally well tolerated, with no drug-related serious adverse events. Few people stopped treatment early because of adverse events in any treatment arm (2 to 4 percent). Besides injection site reactions, the most common adverse events were nose and throat inflammation, diarrhea and headache.
Most participants experienced injection site reactions, but these were usually mild or moderate, lasting an average of three days; pain was the most common complaint. But only two people (less than 1 percent) stopped treatment early for this reason, and most participants reported that they were satisfied with long-acting therapy and would like to continue on it.
Based on the 48-week results showing a slightly lower rate of virological nonresponse with the Q8W regimen, ViiV selected the Q4W schedule for further testing in Phase III studies now under way. But Eron explained that longer follow-up showed that response rates were similar in the Q4W and Q8W groups, and a Phase III study of treatment every eight weeks is being developed.
“The results of LATTE-2 show that a long-acting injectable antiretroviral regimen has the potential to be both highly effective and well tolerated over a long period of time,” Eron said. “These data provide a strong foundation for the ongoing and planned Phase III trials, which will hopefully lead to an effective, well-tolerated alternative to daily antiretroviral therapy.”