Long-Acting Injectable Antiretroviral Safe, Effective

Pam Harrison

July 25, 2016

DURBAN, South Africa — A long-acting injectable antiretroviral regimen suppressed viral loads in patients with HIV to undetectable levels at 48 weeks in a phase 2b study presented here at the International AIDS Conference 2016.

However, rates of virologic nonresponse were higher when the treatment was administered every 8 weeks than when it was administered every 4 weeks.

"It's exciting to confirm the antiviral efficacy and safety of a new long-acting injectable regimen, compared with a standard-of-care oral tablet combination," said session cochair Paula Munderi, MD, from the MRC/UVRI Uganda Research Unit on AIDS in Entebbe, Uganda.

"And it is equally exciting to see that optimal virologic response to a long-acting injectable regimen is maintained over a dosing interval of 48 weeks," she told Medscape Medical News.

"Patients with chronic HIV infection will appreciate having options for treatment that are better adapted to the demands of their lifestyle, since antiretrovirals remain a lifelong therapy for the foreseeable future," she added.

LATTE-2 Trial

In the open-label Long-Acting Antiretroviral Treatment Enabling (LATTE)-2 trial, 309 treatment-naïve HIV-positive adults underwent a 20-week induction phase that consisted of daily oral cabotegravir 30 mg plus abacavir and lamivudine until viral load was undetectable (below 50 copies/mL).

Of these patients, 286 moved on to the 48-week maintenance phase of the study, where they were randomized to long-acting nanosuspension injectable formulations of cabotegravir, an HIV integrase inhibitor, and rilpivirine, a non-nucleoside reverse transcriptase inhibitor, or to oral cabotegravir plus abacavir and lamivudine.

The injectables were administered every 4 weeks to 115 patients and every 8 weeks to 115 patients. The remaining 56 patients received the oral combination.

The median age of the group was approximately 35 years, and the median CD4+ cell count was approximately 500 cells/mm³.

With the injectables, the rate of patients achieving an undetectable load was similar, regardless of dosing schedule.

Table. Percent of Patients With an Undetectable Viral Load

Time Point 4-Week Injectable Regimen, % 8-Week Injectable Regimen, % Oral Regimen, %
Week 32 94 95 91
Week 48 91 92 89

 

However, rates of virologic nonresponse were higher with the 8-week schedule than with the 4-week schedule or with the oral combination (7% vs <1% vs 2%).

In the two injectable groups, safety profiles were similar. Grades 3 and 4 drug-related adverse events (excluding injection-site reactions) were observed in 3% of the 4-week group and 2% of the 8-week group. In contrast, there were no grade 3 or 4 drug-related adverse events with the oral combination.

"Injection-site reactions were common, but most were mild or moderate, and 90% resolved within 7 days," reported LATTE investigator David Margolis, MD, from ViiV Healthcare in Research Triangle Park, North Carolina.

Pain was the most common injection-site reaction, reported by two-thirds of participants. Nodules and swelling were reported less often.

Only two patients in the study cohort withdrew because of injection-site reactions.

Patient-reported satisfaction with the injectable regimen was very high, said Dr Margolis.

In fact, 39 in-depth interviews were conducted with 27 LATTE-2 participants to determine how they felt about the long-acting intramuscular regimen. Results from that study were presented by Deanna Kerrigan, PhD, associate professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

"All reported being satisfied and interested in continuing long-acting injectable antiretrovirals," Dr Kerrigan noted.

The patients indicated that the injectable regimen was convenient and easy to get, compared with having to take a pill every day.

"In many cases, participants reported that long-acting injectable therapy helped them manage stigma," Dr Kerrigan explained. "It was seen as more discrete with less possibility of others discovering one's HIV status."

Some providers expressed concern that candidates for the long-acting injectable regimen might miss their monthly visit, and that would mean they'd miss a whole month of treatment, risking viral rebound.

"I share the concern that patients must not miss a whole month of HIV treatment," said Dr Munderi.

"However, I do not believe that this danger is unique to the injectable mode of delivery. We have certainly known patients to go missing and not pick up their prescription pills for 3 months," she pointed out.

"The main advantage with the injectable regimen, for me, lies in the potential availability of an alternative mode of delivery for a long-term combination therapy that will be better adapted to the demands of certain patients' lives," she said.

Because of the superior virologic response, the 4-week schedule has been chosen for progression into phase 3 clinical trials. However, the 8-week schedule is still under exploration in the LATTE clinical trials program.

LATTE-2 was sponsored by ViiV Healthcare. Dr Margolis is an employee of ViiV Healthcare.

International AIDS Conference 2016: Abstracts THAB0206LB and THAB0204. Presented July 21, 2016.

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