August 8th, 2022

Long-Acting Injectable HIV Therapy for People Who Won’t Take ART?

Atlas. Lee Lawrie and Rene Paul Chambellan, 1937.

HIV treatment is so spectacularly effective that you might be surprised to hear that some people with HIV still have uncontrolled viral replication. We HIV clinicians watch with frustration and sadness as they experience progressive immunodeficiency, complications from advanced HIV disease, hospitalizations, and HIV-related deaths. Plus, while viremic, they continue to risk transmitting the virus to others.

What’s the barrier to successful treatment? In 2022, it’s almost never drug resistance. It’s that they can’t, or won’t, take oral antiretroviral therapy. Excluding those completely out of care (that’s a different problem), I’d estimate from various studies that they typically represent around 5% of a clinic’s population.

The percentage with uncontrolled HIV is higher in places like Ward 86, the safety net HIV clinic at UCSF — around 15% by their estimates. True to its mission, the clinic serves many people struggling with poverty, substance use disorder (especially cocaine and crystal methamphetamine), unstable housing, psychiatric illness, and low medical literacy. That’s why the case series they just published using long-acting cabotegravir and rilpivirine (CAB-RPV) is so remarkable.

That’s right — cabotegravir and rilpivirine for this highly challenging patient population, a group most certainly underrepresented in the pivotal clinical trials ATLAS and FLAIR.

Out of 132 people in Ward 86 referred for CAB-RPV treatment, 51 started injections. Of these, 39 patients had at least two treatments and were included in this report. The good news:  All those with virologic suppression at baseline maintained HIV control during the follow-up, a tribute to the enhanced care provided by the team of clinicians involved in the program.

But by far, the most notable aspect of this report is what happened to the 15 people who were not on suppressive ART — in other words, the group highlighted in the first paragraph of this post, those not taking their meds.

This viremic group had a median CD4 cell count of 99 and a viral load of around 50,000 (with one over a million); a patient with resistance to raltegravir and elvitegravir (harboring the N155H mutation) was also treated. Despite these unfavorable baseline characteristics, 12 of 15 achieved virologic suppression (including the person with N155H), and the other 3 have HIV RNA that has declined by more than 2 log.

Wow.

These exciting results notwithstanding, it deserves emphasis that using CAB-RPV for viremic patients takes us way outside the indications outlined in the FDA approval. This specifically stated that the treatment is for those “who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.”

There are plenty of additional caveats about using CAB-RPV in people not taking oral ART. The study includes just a small number of viremic patients, and the follow-up is relatively short (less than a year). We can’t say whether virologic suppression will be maintained, or what proportion will drop out of care and miss their injections, or how many will develop the much-dreaded two-class drug resistance to both integrase inhibitors and non-nucleoside reverse transcriptase inhibitors — resistance that will make subsequent treatments much more challenging. Plus, payers in some regions may not be as generous in covering treatment for a non-FDA approved indication.

It’s also worth remembering that Ward 86 is a special place, hardly representative of most HIV, ID, or primary care clinics. They have tons of dedicated on-site resources to enhance the care of their difficult-to-reach patient population. This includes doctors, nurses, pharmacists, social workers — a veritable army of people available to support and chase down people who might go astray while on HIV therapy.

Example:  Two of the patients in this report with unstable housing received injections in the community with “street-based nursing services.” (When I wrote “chase down,” this is what I meant.) How many of us HIV providers have access to this kind of wraparound care? In other words, if you’re in a standard ID or HIV clinical practice, don’t try this at home quite yet.

These caveats notwithstanding, I maintain that this novel use of CAB-RPV is highly important, and that it’s critical it be explored further. Up to this point, our options for people who won’t take oral ART have been highly limited. In desperate cases, we’ve even resorted to feeding tubes to administer ART, these placed during prolonged hospitalizations for AIDS-related complications. If CAB-RPV can provide even half the people who won’t take oral ART an effective option, use in this population will be save more lives than CAB-RPV will through its FDA approved indication. After all, those people are by definition doing well on ART!

The alternative to trying this might be an HIV-related death. And no one in 2022 should die of AIDS without our doing everything we possibly can to get them on antiretroviral therapy.

Even if that includes an unapproved use of cabotegravir and rilpivirine.

2 Responses to “Long-Acting Injectable HIV Therapy for People Who Won’t Take ART?”

  1. Gordon Huth, MD says:

    All hospital systems have a few (and some more than a few) AIDS patients who because of mental health issues, IDU or whatever, just can’t get it together to take their oral meds daily or at all. They become (excuse the term) “frequent fliers” in the hospital and cost themselves and the system a great deal of time and dollars and grief. If HCWs could provide DOT with a monthly injectable for this relatively small number of PWAs, find them, dose their medication and try to keep them relatively healthy and out of the hospital, it could be enormously cost-effective. I could even envision pulsing therapy on the same day(s) of the month for everyone in a particular area or system, making the effort even more efficient. I think more than a few patients would appreciate this effort. I suspect some hospital systems might be willing to fund it.

  2. Lludenich says:

    There is not doubt. The ART is a great way to make the control of this particular patient’s.
    We should find a real solution with the vaccination.

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HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

NEJM Journal Watch
Infectious Diseases

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