This article is more than 5 years old. Information may no longer be current.

Long-acting injectable HIV regimen well-tolerated, effective

Add topic to email alerts

Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .

Subscribe

Added to email alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

Back to Healio

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Back to Healio

BOSTON — HIV patients may be able to maintain viral suppression by taking a long-acting injectable regimen for up to 8 weeks at a time, according to results from the LATTE-2 trial. The novel dosing strategy could potentially benefit those with poor adherence to a daily oral regimen.

The investigational integrase inhibitor (INI) cabotegravir (ViiV Healthcare) and the non-nucleoside reverse transcriptase inhibitor (NNRTI) Edurant (rilpivirine, Janssen Therapeutics) have both been developed as once-daily oral tablets, as well as being formulated for intramuscular injection. The extended half-life of the injectable formulations is “largely attributed to the slow release kinetics from the intramuscular depot,” investigator David A. Margolis, MD, from ViiV Healthcare, said during a late-breaker at CROI 2016.

The efficacy of the combination of these drugs was established through 96 weeks in the LATTE-1 study.

“The reason LATTE-2 was conducted was essentially to establish the proof of principle for the first-ever, long-acting HIV treatment regimen,” Margolis said.

The study’s primary objectives included the safety and efficacy of long-acting cabotegravir plus long-acting rilpivirine as maintenance therapy for patients with HIV and to develop a dosing schedule for phase 3 testing.

LATTE-2 was conducted in two parts, according to Margolis. First, during an induction period, a single arm of 309 ART-naive adults with HIV were administered 30 mg cabotegravir plus Epzicom (abacavir/lamivudine, ViiV Healthcare; ABC/3TC) for 20 weeks in order to achieve virologic suppression — or HIV-1 RNA less than 50 c/mL. During the last 4 weeks of the induction period, a daily dose of 25 mg rilpivirine was added to the regimen to assess safety and tolerability.

Next, during a maintenance period, 286 patients who achieved viral suppression were randomly assigned 2:2:1 to receive either a 400-mg intramuscular (IM) dose of cabotegravir plus 600 mg IM rilpivirine every 4 weeks (n = 115); 600 mg IM cabotegravir plus 900 mg IM rilpivirine every 8 weeks (n = 115); or to continue oral dosing with 30 mg cabotegravir plus ABC/3TC (n = 56).

Baseline characteristics were well-balanced across the three study arms, Margolis said.

At 32 weeks, viral suppression was achieved by 95% of participants who received the long-acting injectable regimen every 8 weeks, 94% of those who received the injection every 4 weeks, and 91% of participants who continued with oral therapy.

According to Margolis, there were two protocol-defined virologic failures — one occurring in the 8-week injection arm and another in the oral therapy arm. However, there was no evidence of the emergence of NNRTI, INI or NRTI mutations during the study. The number of participants who reported injection site reactions decreased over time — from 96% on the first day of maintenance therapy to 33% on week 32. The most common injection site reactions were pain (67%), swelling (7%) and nodules (6%). Most injection site reactions were reported as mild or moderate, lasting a median duration of 3 days. Two patients withdrew from the study due to these reactions. Serious adverse events occurred in 6% of patients who received the injections and 5% of patients who were assigned oral therapy; none was drug-related, according to the researchers. There was one fatality, which was unrelated to the study.

Overall, patient satisfaction with injectable dosing was high, Margolis said. However, based on pre-specified criteria, the researchers were unable to settle on one injectable dosing strategy over the other, and further analysis is planned to determine the optimum duration between injections before entering phase 3 testing.

“The LATTE-2 results successfully demonstrate the potential to maintain virologic suppression with long-acting, intramuscular cabotegravir plus rilpivirine, whether dosed every 4 weeks or every 8 weeks,” Margolis concluded. – by John Schoen

References:

Margolis DA, et al. Abstract 31LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 22-25, 2016; Boston.

Margolis DA, et al. Lancet Infect Dis. 2015;doi:10.1016/S1473-3099(15)00152-8.

Disclosure: Margolis is an employee of ViiV Healthcare.