The combination of two long-acting injectable antiretroviral drugs - ViiV Healthcare's experimental cabotegravir integrase inhibitor and Janssen rilpivirine's Nucleoside Reverse Transcription Reverse Transcriptase Inhibitor (ITRNN) - given once every 4 or 8 weeks has maintained the viral suppression as well as a standard oral regimen and appears safe and well tolerated, companies announced this week. These findings from Phase 2 b of the LATTE 2 Study accompany previous reports from the original LATTE study showing that Cabotegravir + oral rilpivirine retains HIV as well as a three-drug therapy regimen with efavirenz but with fewer side effects.
Long-acting drugs may offer a compelling option for people living with HIV who are learning for antiretroviral therapy (ART). These agents have the advantage of being more convenient and have a potential to improve adherence, but the disadvantage is that a long-acting drug can not be easily removed from the body once administered, so it is especially important to establish safety in advance .
The 2 b phase of the LATTE study evaluated Cabotegravir plus rilpivirine as a simple treatment regimen, a two-drug regimen for people who had already achieved undetectable viral load using the standard treatment that uses a combination of at least three drugs in ART, above all, that the two drugs are effective when taken as daily tablets giving the necessary foundations to test their time in action injectable formulations.
Cabotgravir (formerly GSK1265744) is a drug-related integrase inhibitor currently available, dolutegravir (Tivicay), while rilpivirine (Edurant) is an already approved non-nucleoside reverse transcriptase inhibitor.
David Margolis of ViiV / GlaxoSmithKline: Presenting the findings of the 48 week.
The assessment of oral maintenance therapy at the 2014 Conference on Retroviruses and Opportunistic Infections (CROI) and the results of 96th week this year (link opens in another tab, another site, in English); these results were recently published in the October of 2015 Lancet on infectious diseases. (link opens in another tab, another site, in English)
LATTE (LAI116482 study) started with a reception available in the induction period of the 24 week, comparing 3 oral doses of Cabotegravir (10, 30, or 60 mg once daily) or 600 mg once daily of efavirenz (Sustiva ) plus 2 nucleoside reverse transcriptase / nucleotide (NRTI) inhibitors. After 24 weeks, those receiving Cabotegravir with stable viral suppression (<50 copies / mL) had the NRTIs discontinued and replaced with 25 mg rilpivirine once daily throughout the treatment until 96th week.
This analysis included 243 people with HIV without prior historical treatment in the US and Canada. Almost all (96%) were male, about 60% were white, about 30% were black, the mean age was 33 years, and 4% were co-infected with the hepatitis C virus. median T cell count-CD4 was 416 cells / mm 3, and 14% had high viral load (> 100.000 copies / mL). About 60% had initially used tenofovir / emtricitabine (Truvada) while about 40% had used abacavir / lamivudine (Epzicom).
At the end of the induction period of 24 weeks, 86% of participants in the combined cabotegravir in both study arms (with little difference between doses) and 74% in the study arm with efavirenz had undetectable viral load. At 48 weeks, 82% of participants who continued on cabotegravir plus rilpivirine and 71% who had efavirenz assigned to treatment had maintained viral suppression. These differences were not statistically significant, according to the study authors.
At 96 weeks, 76% of cabotegravir recipients and 63% of efavirenz recipients had undetectable viral loads maintained. Looking only at participants who entered the maintenance period, 86% and 83%, respectively, continued viral suppression. At week XN0X the response rates do not seem to improve with higher doses of cabotegravir (96%, 68%, and 75%, using 84, 10 and 30 mg, respectively).
The differences between the 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 the cabotegravir arm and 59% in the efavirenz arm. Among those with viral load > 100.000 copies/ ml, the rates were 50%, 71%, 67% and 88%, respectively. However, the researchers underlined that when stratified by viral load, the difference in numbers in each subgroup were small.
The lower rate of treatment failure in the cabotegravir arm compared to the efavirenz arm was driven by lower virological response rates (10% vs 16%) and fewer withdrawals, due to the occurrence of adverse events (3% vs 13%), the researchers.
Generally Cabotegravir was safe and well tolerated. At 96 weeks, 51% of cabotegravir recipients - again with little difference between doses - and 68% of efavirenz beneficiaries reported adverse effects related to treatment events of any severity. In particular; side effects on the central nervous system such as dizziness (6% vs 23%) and insomnia (4% vs 15%) were more common with efavirenz.
"The results of LATTE indicating that the drug regimen with two drugs using Cabotegravir plus Rilpivirine provides viral suppression that is at least similar to the three drug regimens with efavirenz and two NRTIs during 72 weeks of maintenance therapy in an ART adult population with no previous experience of antiretroviral therapy are elucidated for further evaluation and development of long-acting injectable formulations of cabotegravir and rilpivirine, "the authors concluded.
Injected with long-term action
Since these results confirm that cabotegravir plus rilpivirine form an effective oral maintenance schedule for people who have achieved viral suppression in a standard regimen, the researchers evaluated the timing of the injectable formulations of these drugs in the LATTE Study (NCT02120352).
This analysis included 309 participants who were not previously treated starting treatment for the first time of oral presentation of a three-drug regimen consisting of 30 once-daily cabotegravir plus two NRTIs. After reaching viral suppression, they were randomly assigned to remain on the oral regimen or to receive injections of rilpivirine plus cabotegravir every 4 weeks (Q4W) or 8 weeks (Q8W). Previous research has shown that cabotegravir injectable Remains at therapeutic levels (link opens in another tab, another site, in English) with monthly or quarterly dosages.
After 32 weeks (the primary endpoint), 94% and 95% of participants who received the injections each 4 or 8 weeks respectively, maintained viral suppression, as did 91% of those receiving oral treatment, according to reports from press release issued by ViiV and Janssen. The 2 people who met the protocol defining criteria for virological failure (1 in the Q8W arm injection and 1 in the oral arm) did not show evidence of drug resistance.
People who switched to the Q4W injection schedule reported more adverse events leading to withdrawal than those receiving the medication in the Q8W injection scheme or the oral schedule (5%, 2%, and 2%, respectively). The most common side effect was pain at the injection site (93% of the injection recipients). Two patients in the Q8W arm - but none in the Q4W arm - gave up due to injection intolerance
The results of the study in 32 weeks will be presented at the next scientific conference, according to press releases. Study follow-up will continue throughout the 96 weeks.
Companies are now planning to further evaluate the long-acting injectable solution in a larger scheme in a phase III study.
The long duration of action of cabotegravir and rilpivirine formulations is also being studied for pre-exposure prophylaxis, or PrEP. In animal studies protected by monthly cabotegravir injections in monkeys against infection with a virus such as HIV delivered via rectal exposure or vaginal exposure * link opens in another tab, gold site languages.
The results of the LATTE study "challenge the notion that dual therapy is a realistic option over triple therapy," Mark Alastair Boyd and David Cooper of the Kirby Institute of the University of New South Wales wrote in a few comments to LANCET . "The LATTE Study may therefore not only be the beginning of a new era of long-term intramuscular treatment, a long-term management option against HIV, but also the dawn of an effective and well-tolerated two-drug therapy [NRTI] sparing protease inhibitor patients as well as long-term single tablet oral HAART regimens. "
Translated by Claudio Souza Original in Long-acting Injectable Cabotegravir + rilpivirine Maintains HIV Suppression is 32 Weeks
Reviewed by Mara Macedo in 18 2015 November
Written by Liz Highleymande remedies poe at risk your personal security
DA Margolis, CC Brinson, GHR Smith, WR Spreen, et al. Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (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 a study of two drug injectable 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.