A combination of two long-acting injectable anti-retroviral drugs, cabotegravir and rilpivirine, given once every 4 or 8 weeks, has maintained viral suppression as well as a standard antiretroviral therapy and oral antiretroviral regimen and appears safe and well tolerated, according to results of the LATTE study two studies presented in Conference on Retroviruses and Opportunistic Infections (2016 just completed) Taking place this week in Boston, USA.
Long-acting medications could offer a compelling option for people with HIV who face a lifetime of antiretroviral treatment. These agents have the advantage of being more convenient and potentially increasing adherence, but the disadvantage is that a long-acting drug can not be easily removed from the body, so it is especially important to establish safety in advance.
To this end, the LATTE study (English acronym for long-acting antiretroviral treatment) evaluated by the ViiV Healthcare as well as the experimental integrase inhibitor cabotegravir (formerly GSK1265744) and Edurant, rilpivirine, the Janssen, the class of NNRTIs as a simplified maintenance scheme with two oral dosing drugs for people who had already reached the undetectable viral load using the standard three antiretroviral drugs.
Over the past year, David Margolis has just To present the findings of a study of 96 weeksAt ViiV, showing that in 76% of participants who switched to oral dual therapy of cabotegravir plus rilpivirine was also maintained viral suppression, comparing to 63% of those who adhered to a three-drug regimen containing efavirenz (Sustiva).
The oral combination was safe and well tolerated and was the basis for testing the injectable version of long-acting drugs with cabotegravir formulation and raltegravir in the LATTE 2 study.
Dr. Margolis presented the thirty-two-week results of the LATTE study at 2 at this year's conference.
This phase of the analysis (2b) included 309 people with HIV who had not been treated previously (ART virgins). More than 90% were men, about 80% were white and the mean age was 35 years. At the baseline, the mean CD4 cell count was 489 cells / mm3 and nearly a fifth had a high viral load> 100.000 copies / ml.
Participants in the present open study initiating, for the first time, a three-drug induction scheme consisting of a daily application of 30mg of cabotegravir plus abacavir / lamivudine ( Kivexa ou Epzicom).
Those who achieved viral suppression (<50 copies / ml) during the induction period were randomly assigned to receive intramuscular injections of rilpivirine and cabotegravir every 4 weeks (Q4W) or every 8 weeks (Q8W), or to remain in the same oral regime. Previous studies have demonstrated that injectable cabotegravir Remains at therapeutic levels with monthly or quarterly dosages in an injectable therapy regimen consisting of adding 2 to 3ml in injections of rilpivirine plus cabotegravir in the buttocks. Dr Margolis suggested that thigh injections may make self-administration possible. He said there is some flexibility in dosing so people can apply the injections within a week before or after their scheduled date.
Of the initial 309 participants, 286 achieved viral suppression and were randomized to maintenance therapy. During the maintenance period, 94% of the people who received the injectables every 4 weeks and 95% of the treated each 8 weeks maintained the HIV RNA <50 copies / ml at the thirty second week, in the same way as 91% of those who were in the oral scheme.
There were a small number of participants - one in the cabotegravir arm Q4W, five in the Q8W arm and two in the oral therapy arm - who did not exhibit virological response. Two of these (one in Q8W and one in the oral arm) had been defined by the protocol as virological failure, but had no evidence of resistance to the integrase inhibitor or NNRTIs.
Cabotegravir injectable and rilpivirine were generally safe and well tolerated
Serious adverse events occurred in 6% of those who changed over the course of the study of injectables and 5% of those who remained in the oral regimen; however, these cases were not considered to be drug-related.
The most common reactions related to side effects of the drug were at the injection site, occurring in more than 90% of the patients treated with the injection. In a universe of 4286 injections, 2282 had reactions like pain and swelling. These reactions were usually mild or moderate, usually resolved within one week (mean of three days) and became less common over time, but they led two people to withdraw from the study.
The most common forms of drug-related adverse events other than injection reactions were fever, fatigue, and flu-like illness experienced by 19 participants in injecting drug use and to a person on the oral schedule. Laboratory abnormalities of grade 3 or higher were seen in 16% and 14%, respectively.
Pharmacokinetic analysis showed that long-acting injections maintained cabotegravir concentrations similar to those observed with oral therapy in the original LATTE study. Concentrations started low and then started to rise, and Dr Margolis said they are working on strategies to raise initial concentration levels. Rilpivirine concentrations have risen over time, but he said they were well below the level that could pose a risk to the production of heart problems.
Participants in this study reported a high level of satisfaction with treatment - more than 90% of those receiving long-acting injections reported that they were satisfied, compared with about 70% of those on the oral schedule.
Neither the four-regime nor the eight-week regimen was clearly better. The follow-up of the LATTE 2 trial will continue for another ninety-six weeks and the researchers have a plan to evaluate dosages of even longer durations, at one stage in injectable schemes with longer durations in three trials.
Long-acting formulations of rilpivirine cabotegravir are also being studied for pre-exposure prophylaxis (PrEP) - data that is also being presented later this week.
Translated by Cláudio Santos de Souza from the original CROI 2016: Long-Acting Injectable Cabotegravir + rilpivirine Works Well HIV Maintenance Therapy on 24 February 2016
Margolis DA et al. Cabotegravir + rilpivirine the long-acting maintenance therapy: LATTE-week 2 32 result. 2016 Conference on Retroviruses and Opportunistic Infections (CROI), Boston, abstract 31LB, 2016.
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