The combination of two injectable antiretroviral long duration of action - The inhibitor cabotegravir experimental integrase ViiV Healthcare and NNRTI (inhibitor Transcritease Reverse There analogue of Nucleoside) of Janssen rilpivirine - given once every 4 and 8 weeks has kept the viral suppression as well as a standard oral regimen and appears safe and well tolerated, the companies said this week. These findings from Phase 2 b Study LATTE 2 follows previous reports of the original LATTE study showing that oral Cabotegravir + rilpivirine remains suppressed HIV as well as a therapy scheme with three drugs with efavirenz, but with fewer side effects.
Long-acting drugs may offer an attractive option for people living with HIV focused on lifelong antiretroviral therapy (ART). These agents have the advantage of being more convenient and has a potential capable of improving adhesion, but the disadvantage is that a long-lived drug can not be easily removed from the body once administered, so it is particularly important to ensure the safety in advance .
The 2 step b latte study evaluated Cabotegravir more rilpivirine as a simple processing scheme, a two drug regimen for individuals who had achieved an undetectable viral load using the standard treatment uses a combination of at least three drugs on ART, proof, above all, that the two drugs are effective when taken as pills daily giving the necessary basis to test their time at work injectable formulations.
Cabotegravir (formerly The GSK1265744) is an integrase inhibitor associated with the drug now available at the moment dolutegravir (Tivicay), whereas rilpivirine (Edurant) is already approved reverse transcriptase inhibitor non-nucleoside analog.
David Margolis of ViiV / GlaxoSmithKline:Presenting the findings of 48ª week.
The assessment of oral maintenance therapy at the Conference on Retroviruses and Opportunistic infections 2014 (CROI) and96ª of the week results this year(link opens in another tab, another site, in English); These results were recently published in the edition ofOctober 2015 theLancet on infectious diseases. (link opens in another tab, another site, in English)
LATTE (LAI116482 study) began with a reception in the 24ª week induction period, comparing 3 oral doses of Cabotegravir (10, 30, or 60 mg once daily) or 600 mg once efavirenz day (Sustiva ) 2 more reverse transcriptase inhibitors, nucleoside / nucleotide (NRTIs). After 24 weeks, they received Cabotegravir stable viral suppression (<50 copies / mL) had NRTI suspended and replaced by 25 rilpivirine mg once daily throughout the treatment until week 96ª.
This analysis included 243 people with HIV with no history prior therapy in the US and Canada. Almost all (96%) were male, about 60% were white, about 30% were black, the average age was 33 years 4% were co-infected with hepatitis C. The line Mid-CD4 T cell count was 416 cells / mm 3 and 14% had high viral load (> 100.000 copies / mL) .cerca of 60% had used initially tenofovir / emtricitabine (Truvada) while about 40% had used abacavir / lamivudine (Epzicom).
At the end of 24 week induction period, 86% of participants cabotegravir combined in both study arms (with little difference among the doses) and 74% in efavirenz study arm had an undetectable viral load. In 48 weeks, 82% of participants who continued in the rilpivirine cabotegravir and 71% who had efavirenz assigned to treatment had maintained viral suppression. These differences were not statistically significant, according to the study authors.
In 96 weeks, 76% of cabotegravir recipients and 63% of efavirenz recipients had kept the undetectable viral loads. Just looking for participants who entered the maintenance period, 86 83% and% respectively, continued viral suppression. In 96ª week response rates appears to improve with higher doses of cabotegravir (68% 75% and 84% using 10, 30 and 60 mg, respectively).
The differences enter responses were more pronounced in patients with high viral loads. Among people with HIV RNA <100.000 copies / ml at baseline, response rates were 71% 75%, and 88% in 10, 30 and 60 mg doses in cabotegravir arm and 59% in the efavirenz arm. Among those viral comcarga> 100.000 copies/ ml, the rates were 50%% 71, 67 88% and% respectively. However, the researchers pointed out that when stratified by viral load, the difference of the numbers in each subgroup were small.
The lower failure rate for treating cabotegravir arm compared to the efavirenz arm was driven by indices lower virologic responses (10% vs 16%) and fewer withdrawals due to adverse events (3% vs 13%), the researchers.
Generally Cabotegravir was safe and well tolerated. In 96 weeks, 51% of cabotegravir of beneficiaries - again with little difference between doses - and 68% of efavirenz recipients reported adverse effects associated with handling events of any severity. In particular; side effects on the central nervous system such as dizziness (% vs 6 23%) and insomnia (% vs 4 15%) were more common with efavirenz.
"The results latte indicating that the drug regimen with both drugs, by using Cabotegravir more rilpivirine provides viral suppression which is at least similar to the drug regimens with three drugs with efavirenz and two NRTIs during 72 week maintenance therapy in a HAART in adult population with no previous experience of Antiretroviral Therapy is instructive to carry out further evaluation and development of injectable formulations long-term action with cabotegravir and rilpivirine, "concluded the study authors.
Injected with long-term action
Since these results confirm that cabotegravir more rilpivirine form an effective oral maintenance schedule people who have achieved viral suppression in a standard layout, researchers evaluated the time of action of injectable formulations of these drugs in LATTE Study (NCT02120352).
This analysis included 309 participants who were not previously treated, starting with the first treatment of the oral presentation with a drug regimen consisting of three drugs 30 mg once daily cabotegravir plus two NRTIs. After reaching viral suppression, they were randomly assigned to stay in the regime orally or receiving injections of more cabotegravir rilpivirine each 4 weeks (Q4W) or 8 weeks (Q8W). Previous research has shown that injectable cabotegravirRemains at therapeutic levels(link opens in another tab, another site, in English) with monthly or quarterly doses.
After 32 weeks (the primary endpoint), 94% and 95% of participants who received the injections every 4 and 8 weeks, respectively, sustained viral suppression, as did 91% of which received oral treatment, according to communiqués press issued by ViiV and Janssen. The 2 people who met the protocol definition of virologic failure criteria (1 in Q8W arm injection and 1 arm orally), show no evidence of drug resistance.
People who switched to Q4W injections scheme reported more adverse events leading to withdrawal than those receiving medication in Q8W injections scheme or oral scheme (5%% 2 and 2%, respectively). The most common side effects were pain at the injection site (93% of the injection recipients). Two patients in Q8W arm - but none in Q4W arm - dropped out due to intolerance injection
The results of the study in 32 weeks will be presented at upcoming scientific conference, according to press releases. The following study will continue along the 96 weeks.
Companies are now planning to evaluate in more detail the injectable solution long-term action in a larger scheme, a phase III study.
The long duration of action of cabotegravir and rilpivirine formulations are also being studied for pre-exposure prophylaxis, or PrEP. In animal studies cabotegravir protected by monthly injections of monkeys against infection with a virus such as HIV delivered viaexposure for rectal or vaginal exposure * link opens in another tab, gold site languages.
The results of the study LATTE "challenge the notion that dual therapy is a realistic option in relation to triple therapy," Mark Alastair Boyd and David Cooper of the Kirby Institute of the University of New South Wales wrote some comments on the LANCET . "The Study LATTE can therefore not only be the beginning of a new era of long-acting treatments intramuscularly, long-term management option for HIV, but also the dawn of an effective and well-tolerated two drug therapy [NRTI] sparing patients protease inhibitors and oral HAART regimens single tablet long term. "
Translated by Claudio Souza Original inLong-acting Injectable Cabotegravir + rilpivirine Maintains HIV Suppression is 32 Weeks
Reviewed by Mara Macedo in 18 2015 November
Written by Liz Highleymande remedies puts at risk their safety pers
THE Margolis, DC Brinson, GHR Smith, WR Spreen, et al. Cabotegravir plus rilpivirine, once a day, after induction with nucleoside reverse transcriptase cabotegravir plus inhibitors in antiretroviral-naive adults with HIV-infection 1 (LATTE): a randomized, phase 2b, dose-ranging trial.Lancet Infectious Diseases15 (10): 1145-1155. October 2015.
MA Boyd and DA Cooper. The LATTE study: the provocative brew (Commentary).Lancet Infectious Diseases 15 (10): 1116-1117. October 2015.
ViiV Healthcare. ViiV Healthcare Announces positive headline results from the study of two injectable drug regimen for HIV maintenance therapy.Press release. November 3, 2015.
Janssen Sciences Ireland UC. First Investigational Long Acting Injectable All HIV Combination Regimen Study Results Announced at 32 Weeks. Press release. November 3, 2015.