30A cabotegravir + prolonged-acting rilpivirine injection shows good results at 96 weeks
Two long-acting injectables, cabotegravir and rilpivirine given once every 4 or 8 weeks maintained viral suppression by about 90% of those who started treatment with an undetectable viral load, according to the latest results of the LATTE trial -2, presented today at9A International AIDS Conference Society on HIV Science (IAS 2017), In Paris, France. Modern antiretroviral drugs are highly effective if taken as indicated on a daily basis. But maintaining good long-term adherence can be challenging, and long-acting injectable drug formulations may offer an alternative for people facing a treatment lifespan.
"These data provide a solid foundation for ongoing and planned 3 phase trials, which hopefully will lead to an effective and well tolerated alternative to daily antiretroviral therapy." Dr. Joseph Eron
Joseph Eron of the University of North Carolina at Chapel Hill has presented findings from the 96 weeks study LATTE-2, which is evaluating a regimen of maintenance of two drugs of the experimental integrase inhibitor of ViiV Healthcare cabotegravir and non-reverse transcriptase inhibitor Nucleoside analog of Janssen (NNRTI) rilpivirine, which is approved as an oral formulation(Edurant,Also in combination pillsEviplera, and Complera).
To ensure the baseline efficacy and tolerability of this regimen before testing injectable formulations, the previous LATTE-1 trial evaluated oral cabotegravir plus rilpivirine as a simplified two-drug maintenance regimen for people who achieved undetectable viral load using antiretroviral therapy Three-drug standard (ART).
In 2015, David Margolis of ViiV shows that 76% of participants who switched to cabotegravir plus oral rilpivirine maintained sustained viral suppression compared to 63% of those who remained on a three-drug regimen containing efavirenz (Sustiva).
These results established the basis for the 2b LATTE-2 phase test by testing long-term nano-suspension formulations of cabotegravir and rilpivirine administered as intramuscular injections to the buttocks.
The injections currently must be administered by a health professional, although self-administration is potentially possible in the future, said Dr. Eron.
This open study enrolled 309 participants in Europe and North America who were being treated for HIV the first time. More than 90% were men, about 80% were white and the mean age was 35 years. The average CD4 count was about 500 cells /mm3And about one in five had a high level of RNA induction regimen of three drugs with oral cabotegravir of 30 mg plus abacavir / lamivudine (the drugs inKivexa ®, and Epzicom).
After 20 weeks, those with viral load below 50 copies / ml (undetectable by the usaxo test standard) were randomly assigned to remain on the same oral regimen or switch to cabotgravir and prolonged-acting rilpivirine injections; 286 people have met this criterion. The last group received 400 mg of cabotegravir plus 600 mg of rilpivirine administered every 4 weeks (Q4W), or 600 mg of cabotegravir plus 900 mg of rilpivirine administered every 8 weeks (Q8W).
Dr. MargolisReported results of 32 weeks from Latté-2(The primary endpoint) at the Conference on Retroviruses and Opportunistic Infections, which shows that 95% of participants who switched to the injectable combination Q8W and 94% of those treated with the Q4W regimen had maintained undetectable viral load as well as 91% Of those who remained in the oral regimen.
Translator's Note: Here is an observation regarding possible cases of therapeutic failure: I observe, While I translate, That the ambitious goal, which is the Undetectable viral load, Seems to be a very distant goal! When the Chuchu Pastel closed the AIDS house and we were banished to the Emílio Ribas hospital I saw, and I heard from some doctors (I'm great to talk) that Emílio Ribas's doctors showed some frustrations because, unlike patients ( I am generalizing, but I know there are exceptions) of Emílio Ribas, the patients who, like me, came from the AIDS House, had no commitment to the care of their own health and did not lack to consult, they did not stop, mostly , With medications on weekends, and again there are exceptions because they also lacked the consultations and that, when they were missing, the cases were mostly due to a just reason, such as the death of someone who loved them (mother, HIV positive girlfriend , Friends, and those who could not leave their homes because of bowel disorders or something related to very low CD4 counts had a similar picture to AIDS.
Most participants maintained viral suppression over two years with the cabotegravir regimen and rilpivirine, Dr. Eron reported today. At 96 weeks, 94% of people in the Q8W injectable combo and 87% in the Q4W regimen still had undetectable HIV RNA, compared to 84% in the continuous oral regimen.
Three patients receiving cabotegravir and rilpivirine injected experienced a protocol-defined virologic failure: two in the Q8W regimen (one at week 4, one at week 48) and one at oral regimen. No one receiving the Q4W regimen experienced a treatment failure. There were no additional cases of treatment failure between 48 week and 96 week.
Cabotegravir injectable and rilpivirine were generally safe and well tolerated. Serious adverse events occurred with similar frequency in the three treatment groups, but none of them were considered to be related to the medications. Eleven people stopped treatment early due to adverse events (2% in the Q8W group, 7% in the Q4W group and 2% in the oral regimen). In addition to injection site reactions, the most frequently reported adverse events were nose and throat inflammation, diarrhea, and headache.
Almost all participants reported reactions at the injection site, but were generally mild or moderate and transient, with an average duration of three days. Only two people (less than 1%) discontinued treatment for this reason. Pain was the most common complaint.
Despite frequency of injection site reactions, participants reported being highly satisfied with long-acting therapy and would like to continue with this. "I realized how good it was not to have to take pills every day and the sense of freedom from not having to stay connected to oral therapy," Dr. Eron said.
"Long-acting injectable drug therapy, given Q8W or Q4W, demonstrated high antiretroviral response rates and was well tolerated for 96 weeks," the researchers concluded.
Weekly injections Q8W and Q4W maintained levels of cabotegravir similar to those observed with oral administration. However, since the monthly dosage resulted in a slightly lower non-virological response rate at week 48, the Q4W regimen is being further evaluated in ongoing 3 phase studies.
Dr. Eron explained that with long-term follow-up, additional participants in the Q8W regimen achieved viral suppression. The Q8W dosing evaluation is in progress and a 3 phase study is being developed, He told reporters. However, administration every month allows more tolerance when a person eventually misses an injection.
"The results of LATTE-2 show that an injectable antiretroviral regimen with cabotegravir and long-acting rilpivirine has the potential to be highly effective and well tolerated over a long period of time," Eron said. "These data provide a solid foundation for ongoing and planned 3 phase trials, which hopefully will lead to an effective and well tolerated alternative to daily antiretroviral therapy."