Can people without viral suppression benefit from Cabenuva?
According to a small pilot study presented at the 24th International AIDS Conference in Montreal and published in Clinical Infectious Diseases.
Researchers at Ward 86 HIV Clinic in San Francisco found that 80% of people who started Cabenuva with a detectable viral load achieved and maintained viral suppression, some of them for the first time.
Injectable cabotegravir, a new integrase inhibitor from ViiV Healthcare, combined with rilpivirine (NNRTI), a non-nucleoside reverse transcriptase inhibitor from Janssen, is the first comprehensive antiretroviral therapy that does not require daily pills. The treatment consists of two intramuscular injections in the buttocks given by a medical professional once a month or every two months.
Two phase III clinical trials have shown that Cabenuva leads to long-lasting viral suppression. The ATLAS study evaluated the diet as a maintenance treatment for treatment-experienced people who already had a stable undetectable viral load on a standard oral diet. The FLAIR study recruited previously untreated people, but they achieved viral suppression on a temporary oral regimen before switching to injections.
The Food and Drug Administration (FDA) has approved Cabenuva only for people whose HIV is currently under control on a stable oral regimen, has no history of treatment failure, and has no evidence of resistance to both drugs.
Katerina Christopoulos, MD, MPH, Monica Gandhi, MD, MPH, and colleagues at Zuckerberg San Francisco General Hospital (SFGH) wanted to know if Cabenuva might be a feasible option for people unable to achieve or maintain viral suppression by due to difficulty in adhering to oral treatment.
Researchers evaluated a demonstration project that included 51 people who started the long-acting regimen at SFGH’s Ward 86 HIV Clinic between June 2021 and April 2022. Of these, 39 had at least two treatment visits. follow-up injection. A majority (24 people) had viral suppression and high CD4 counts (median 706 cells) at the start of injections, but 15 had detectable viral load and substantial immunosuppression (median 99 CD4 cells).
Fully agree @paulsaxMD; that’s why we’ve started very hard to reach out to patients who have issues adhering to cabotegravir/rilpivirine IM as “Hail Marys” when needed: https://t.co/rVWmJAC2Z9 https: //t.co/93wZtMjb6l
— Monica Gandhi MD, MPH (@MonicaGandhi9) August 8, 2022
Ward 86 is a safety clinic for low-income people living with HIV who are uninsured or dependent on Medicaid or Medicare. Overall, the clinic serves over 2,400 clients. About 10% have chronic unsuppressed HIV, a group with high rates of substance abuse, mental illness and homelessness. In 2019, Ward 86 launched the POP-UP program to provide care to unstable people who find it difficult to engage in mainstream HIV care.
Most of the participants in this analysis were men, with the exception of one transgender woman and two cisgender women. The median age was 46; none were under 30 years old. About 60% were black or Latino, and three were monolingual Spanish speakers. Just over 40% were homeless or precariously housed, and half said they currently use stimulants. People with rilpivirine resistance were excluded, but one person had an integrase inhibitor resistance mutation.
Pilot participants typically begin Cabenuva injections without an oral lead-in period using cabotegravir and rilpivirine pills, which have been shown to be safe and effective. Viral load testing is done monthly, with resistance testing done at the second injection visit if it remains detectable. Participants who maintain viral suppression after six months of monthly injections can switch to the bimonthly schedule, which was found to be equally effective in the ATLAS-2M trial. People who expect to miss an injection visit by more than seven days are advised to continue with their previous oral regimen until injections resume.
The program offers a wide range of support. Participants can come to the Ward 86 clinic for their injections at any time on the designated day. A bilingual pharmacy technician calls or texts to remind people of upcoming visits or to follow up if they miss an appointment. If a person cannot be contacted, the staff tries to reach them in person. Clinic staff develop individualized plans for those without viral suppression, which may include community support, case managers, home care, street nursing services, and financial incentives for visits and blood draws . Two homeless people in this analysis received Cabenuva injections and viral load monitoring at a community clinic or from a mobile harm reduction van.
Of the 24 people who started Cabenuva with an undetectable viral load, 100% maintained viral suppression after a median of six injections, consistent with results from the ATLAS and FLAIR trials.
But the most exciting finding is that 12 of the 15 people (80%) who started with a detectable viral load achieved and maintained viral suppression after a median of six injections, and the other three had a decline of at least 2 log viral load. . Two of those people had been living with HIV for more than 10 years and had never achieved viral suppression before, the researchers noted. One of them, the person with the basic resistance mutation, has now had an undetectable viral load for more than eight months.
Overall grip was good. Most participants (87%) showed up on time for all injection appointments. One person was late for one injection and two were late for two injections. A man traveled to his home country and took oral antiretrovirals while he was away. All still had viral suppression after the delayed visits. Another person was seven days late for an appointment at the data deadline for this analysis.
Cabenuva was safe and generally well tolerated. Injection site reactions were mostly mild to moderate, but one person developed cellulitis at the injection site. No one has decided to quit the injectable diet due to side effects.
“This small demonstration project of [long-acting injectable treatment] in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence issues,” the authors concluded. ‘study.
They noted that five participants were receiving other long-acting injections (psychiatric drugs or naltrexone to manage alcohol or opioid use disorders), underscoring the promise of benefiting from attending further visits. injection to deliver long-acting anti-HIV treatment.
The researchers acknowledged that Cabenuva might not be an option for people who don’t have access to such intensive support. San Francisco offers excellent HIV care and the city provides extensive services for homeless people. Unlike many other states, California covers Cabenuva through Medicaid and its AIDS Drug Assistance Program (ADAP). Most people on Medicare had their copayments covered by ADAP. But getting pre-approval for private insurance coverage could be a challenge, because the FDA’s indication for Cabenuva doesn’t include people without viral suppression.
Although these results are promising, the approach warrants caution because inconsistent use of Cabenuva could lead to dual resistance to NNRTIs and integrase inhibitors that limits other treatment options.
“Ward 86 is a special place, barely representative of most people living with HIV, ID [infectious disease] or primary care clinics,” wrote Paul Sax, MD, of Brigham and Women’s Hospital in Boston, in a blog post about the study. “They have tons of dedicated resources on hand to improve care for their hard-to-reach patient population. This includes doctors, nurses, pharmacists, social workers – a veritable army of people available to support and chase people who might go astray during their HIV treatment… How many of us, providers of HIV, do we have access to this type of wraparound care? In other words, if you’re in standard ID or HIV clinical practice, don’t try this at home just yet.
“So far our options for people who will not be taking oral ART [antiretroviral therapy] have been very limited,” he continued. “The alternative to trying this could be an HIV-related death. And no one in 2022 should die of AIDS without us doing all we can to put them on antiretroviral treatment. Even if that includes unapproved use of cabotegravir and rilpivirine.
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