Long-acting injectable treatment maintains viral suppression
A combination of two once-a-month, long-acting injectable anti-HIV drugs showed a very low rate of therapeutic failure and a favorable safety profile, according to the results of two phase III trials presented yesterday Conference on Retroviruses and Opportunistic Infections (CROI 2019) in Seattle.
Dual injections of cabotegravir, an experimental integrase inhibitor and the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine, currently available as a pill (Edurant), maintained viral suppression among people with treatment experienceviral suppression among people with treatment experience, changing from a standard oral regimen and between previously untreated patients after a short induction period of three drugs.
In addition, the study participants expressed a high level of satisfactiona high level of satisfaction with monthly injections compared to the daily pills, and almost everyone said they would rather use the injectable method, reported Dr. Susan Swindells of the University of Nebraska Medical Center and Dr Chloe Orkin of the Queen Mary.
University of London.
Phase II LATTE studies have previously shown that a simplified oral regimen of cabotegravir plus rilpivirine is effective as maintenance therapy. This supported the evaluation of injectable formulations of the two drugs in previously untreated patients. As reported at the International AIDS Conference of 2016, 91% of people who received injections every 4 weeks and 92% of people who did this every 8 weeks undetectable viral load in week 48.
This set the stage for larger phase III studies. ATLAS (Antiretroviral Therapy as a Long-Term Suppression) evaluated cabotegravir plus injectable rilpivirine in people who switched from a standard oral antiretroviral combinationoral antiretroviral standard with undetectable viral load oral antiretroviral with undetectable viral load, while the FLAIR (First Long-Term Injectable Regimen) tested the injectables in people who started treatment for HIV. the first time.
Cabotegravir and rilpivirine were administered as two jabs intramuscular, the buttocks being the preferred injection site. All injections were given by health professionals. Patients were asked to return to their clinics each monthreturn to their clinics each month and received a window of seven days to do so. Adherence was good in both studies, with almost all participants receiving monthly treatment in this window.
The use of injectable therapy would be "a major paradigm shiftgreat paradigm shift"In the way we offer treatment, according to Orkin. "This can be done - we did not do it on HIV, but it is done in other areas of medicine," she said, noting that long-acting depot formulations are widely used for psychiatric drugs and contraception is commonly administered as injections every month or two.
Switching to injectables
The ATLAS study, presented by Swindells, included 616 patients with treatment experience. One third were women, two thirds were white, about one quarter were black, and the median age was 42 years. They were on antiretroviral therapy for an average of four years, all had viral suppression and the mean CD4 count was 653 cells / mm3.
At the beginning of the study, half were taking NNRTI-based schemes, one-third were taking integrase inhibitors and 17% were in protease inhibitors. They were randomly assigned to remain on their current oral regimen or switch to cabotegravir injectable and rilpivirine. To ensure safety, participants in the last group took cabetgravir and rilpivirine pills for one month before switching to injections.
Undetectable Viral Load - More information here.
The Undetectable viral load, defined as HIV RNA in 50 copies / ml or more, were very low in both groups: 1,6% with cabotegravir injectable and rilpivirine versus 1,0% with continued oral regimen. Virologic success rates were 92,5% and 95,5%, respectively. These results showed that injectables were not inferior to continuous oral therapy.
Three individuals who received the injectables (two from Russia and one from France) confirmed therapeutic failure - translator's remark: They speak of virological failure, as if the virus had failed. In fact the virus WON these little skirmishes and therefore I am revising text by text until there is no more virological failure.
Failure, or bankruptcy, is therapeutic, HIV was able to "dribble the drugs, replicate and develop resistance to this medication / therapeutic system, with return of detectable viral load, and only they and God know what the resulting viral load levels were of these failures at weeks 8, 12 and 20 and showed evidence of reverse transcription or association mutations of integrase resistance. All had HIV 'A' subtypes.
Starting with injectables
The FLAIR study, presented by Orkin, included 556 people initiating their first treatment for HIV. Just over 20% were women, almost three quarters were white, 18% were black and the average age was 34 years. At the start of the study, a fifth had a viral load of 100.000 copies / ml or greater and the median of the CD4 count was 444 cells / mm3.
Participants started with a regimen of three co-formulated dolutegravir / abacavir / lamivudine induction drugs (Triumeq) for 20 weeks to reduce virus levels. They were then randomized to either stay on this regimen or switch to cabotegravir injectable and rilpivirine, again starting with oral formulations of these drugs for the first month.
Here too, non-response rates were low, in 2,1% in the injectable group and 2,5% in the oral therapy group. The virological success rates were of 93,6% and 93,3%, respectively, again demonstrating non-inferiority. Three people, all from Russia and with 'A' HIV subtypes, confirmed virological failure and showed evidence of resistance-associated mutations.
Safety and satisfaction
In both studies, pharmacokinetic data showed that concentrations of cabotegravir and rilpivirine in the blood remained above the effective thresholds throughout the study and were similar to the levels achieved with the corresponding oral formulations.
Treatment was generally safe and well tolerated. Serious adverse events were rare among people using cabotegravir and rilpivirine (none in ATLAS and one in FLAIR).
Hypersensitivity, Pain and Interruptions of Injection Therapy
There were no cases of drug hypersensitivity or hepatic toxicity. In both trials, 3% of participants discontinued treatment with injectables due to adverse events.
Injection site reactions - predominantly pain - occurred in 20% to 30% of participants.
These were more common at baseline, were generally mild or moderate, and improved over time with an average duration of three days.
Four people in ATLAS and three in FLAIR withdrew due to injection site reactions.
The researchers also assessed patient satisfaction and preferences, finding that those who received the injectables were more satisfied with the treatment.
Satisfaction with long-acting injectable treatment increases gradually
The increase in satisfaction was especially noteworthy in ATLAS, where participants were withdrawing from daily oral therapy. The vast majority said they preferred injectables instead of pills (86% of all patients and 97% of survey respondents in ATLAS; 91% and 99%, respectively, in FLAIR).
Swindells acknowledged that, as a supplier, he found it surprising that some patients preferred injections to pills, but they preferred it.
Long-acting injectable treatment facilitates and removes stigma from work stoppage to give continuous course of treatment. Long-acting injectable treatment prevents this
"They like not to have to worry about taking the pills every day ... they get the injection and they're good," she said. "They do not have to think about having HIV every day, they do not have to worry about coworkers or housemates seeing their pill bottles - maybe there's some relief from the HIV stigma if they do not have to think about it every day" .
You see, I had a drug routine that led to the publication of this photo as a "warning shot," explaining that this was the image of my treatment monthly.
But I made a mistake and I agreed to a suggestion of my friend and sister by heart Beatriz PachecoBeatriz Pacheco, which made me understand that in one way or another I stigmatized myself and all of us, as well as being frightened, PANIC(!!!) and left newly diagnosed people newly diagnosed inconsolable with this image and, in the name of common sense, I removed the image.
My treatment these days is composed of what you can see in two images:
- Morning Treatment:
- It is simpes for those who have already taken even more of 40 tablets in a day, including the old formulations and presentations of AZT and DDI (Videx) whose package leaflet was actually a THREAT with a very simple collagen effect: Pancreatitis Fulminant
And this is my nighttime medication: => => =>
Swindells S et al. Cabotegravir + prolonged-acting rilpivirine as maintenance therapy: results from the 48 week of ATLAS. Conference on Retroviruses and Opportunistic Infections, Boston, abstract 139 LB, 2019.
Orkin C et al. Long-acting cabotegravir + rilpivirine for HIV maintenance: FLAIR week 48 results. Conference on Retroviruses and Opportunistic Infections, Boston, abstract 140 LB, 2019.