Monthly Dosing Drug Raises Hopes and Concerns

Cabotegravir suppresses HIV but patients, doctors differ on risks

The investigative anti-HIV agent cabotegravir, plus ripivirine – given as a once-monthly intramuscular injection – appears to control viral replication at undetectable levels, but the delivery of the antiretroviral integrase inhibitor has raised some concerns among patients and physicians, researchers reported here.

Remarkably, what most concerns patients – injection site pain and discomfort – is not what worries physicians who express fears that patients won’t return for treatments or there could be long-lasting allergic reactions to a drug that stays on board for weeks, saidDeanna Kerrigan, PhD, associate professor of health, behavior, and society at Johns Hopkins University Bloomberg School of Public Health.

“Long acting injectable antiretroviral therapy was preferable to a daily oral regimen among people living with HIV participating in a phase IIb trial given its practical and emotional benefits,” Kerrigan said. “Further research is needed regarding appropriate candidates for long-acting injectable antiretroviral therapy, including among women and ‘non-adherent’ populations.”
In her oral presentation at the International AIDS Conference, Kerrigan reported on how 27 patients and 12 clinicians described use of the long-lasting agent after 32 week of treatment in a phase II trial. In some patients injections were delivered monthly; in others it was injected every other month. In phase III trials expected to begin last this year, the monthly dosing will be tested, said David Margolis, MD, MPH, director of HIV drug development at ViiV Healthcare, Chapel Hill, N.C.
The patients were from Spain and the U.S., and all but two were men, mostly men who have sex with men. One of the patients was a heterosexual man; both women were heterosexual.
About 82% of the patients reported injection site pain as their major concern about receiving the injections, although most thought the pain was a minor inconvenience. About 17% of the patients found the pain was moderate. But Kerrigan quoted one participant from Spain as saying: “One day (of pain) is nothing … it’s as if you have a day with a headache. You take ibuprofen and that’s it. You put up with it. It’s temporary.”
Kerrigan said that overall, the patients endorsed the treatment because they perceived it was more convenient than taking daily pills; it provided greater confidentiality and privacy and provided some relief from the unwanted daily reminder of their HIV status. They said they perceived that the monthly injections were less stigmatizing and created less pressure on them personally to remember to take their medication.

“Patients felt very comfortable coming to the clinics; they expressed feeling well-treated, respected and support,” she said. However, some patients said they were questioned by friend and co-workers about their numerous doctors’ visit so some made up excuses such as having to meet a roofer or a plumber.
Kerrigan said the patients said that the injections would benefit “everyone” living with HIV who were tolerant of needles. The treatment might also especially benefit younger people or those with adherence issues.
While the clinicians surveyed through the structured interviews were supportive of the injections they did express some concerns:
The therapy needed to be considered on a case by case basis.
Many patients can take pills just fine.
That even with injections, patients still need to come to the clinic as scheduled.
They also had concerns about development of resistance and clinical management.
She quoted one provider from Spain: “The fear is that the patient does not reappear … [and] after the injection if there is an allergy or intolerance, the medication cannot be removed. It may be many months without really knowing its secondary effects.”
Margolis, who reported on the 48-month results in a second presentation at the oral session, said that there have not been patients who failed to show up for their scheduled treatment.

In the LATTE-2 extension trial, researchers examined the use of cabotegravir plus rilpivirine as maintenance therapy. Patients were first enrolled in a run-in period in which they were treated with once daily cabotegravir plus abacavir and lamivudine for 20 weeks to determine tolerability to cabotegravir. During the last 4 weeks rilpivirine was added to the regimen to ensure patients tolerated that drug as well. They patients were randomized to continue on the oral regimen or receive once-monthly dosing or dosing every 8 weeks.
At 48 weeks, 89% of the 56 patients on the oral regimen had suppressed HIV to undetectable levels, assessed using the 50 copies/mm3 assay; 91% of the 115 patients assigned to every 4 weeks achieved undetectable viral loads; 92% of the 115 patients assigned to every 8 week dosing achieved undetectable virus, Margolis said.
In commenting on the study, session co-moderator Paula Munderi, MD, head of the HIV Care program of the MRC/UVRI Uganda Research Unit on AIDS, in Entebbe, Uganda, told MedPage Today that the concerns of clinicians about whether patients would return for their scheduled injections might be dependent upon the population. “In my clinic, patients believe we are helping them with their disease. I have a lot more women in my clinic and women, in general, have much better health-seeking behavior than men.”
She said that most of the complaints about injection paid was from men, but women have been getting injections for depot shot for birth control for many years and handle those injections well. “Most of the concerns are the providers projecting onto patients,” she said, “which is something we tend to do. Sadly.”
Munderi said, “a certain type of patient who wants a break from pills would be a candidate for the monthly injection.” The real question, however, is whether the company would make the injection affordable, especially for low or middle income nations.

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