Jitters Over New Two-Drug HIV Regimens

Heather Boerner

November 11, 2019

PORTLAND, Oregon — The patient chart that Jason Farley, PhD, ANP-BC, from Johns Hopkins University in Baltimore, was looking at was long — 20 years — with records of the drug-resistant mutations the patient’s virus harbored and a long history of viral suppression on his current regimen.

But renal and other concerns suggested a change, and Farley took the leap to transfer the patient to a newer two-drug regimen of dolutegravir plus rilpivirine (Juluca, ViiV Healthcare).

“He should have been suppressed,” Farley said. But then "he began blipping."

First, his viral load jumped to 200 copies/mL, and then to 300 copies/mL. After Farley added emtricitabine and tenofovir alafenamide (Descovy, Gilead Sciences) to the patient's regimen, his viral load returned to undetectable levels.

The patient had undergone viral resistance testing before the switch. And after the blips started to appear, he underwent DNA testing so that Farley could look for archival resistance mutations. But he found nothing.

"There was something hidden that we could not determine, that he had resistance to," Farley said here at the Association of Nurses in AIDS Care (ANAC) 2019 conference. "Even if you do all your due diligence with your viral resistance profiles, there were things we did not know back in the day that now we might need to search for."

As new two-drug regimens show success in clinical trials and gain approval from the US Food and Drug Administration, clinicians are starting to look at cutting the number of medications patients take for HIV.

But after previous two-drug regimens failed to fully suppress the virus and with patients doing well on three-drug regimens, care teams are grappling with when and with which patients to take the leap.

More Meds, More Problems

Rates of polypharmacy are typically the same in people living with HIV and those in the general public, said Jennifer Cocohoba, PharmD, from the University of California, San Francisco.

A study of a Veterans Administration (VA) system cohort of 9473 people with and 39,812 without HIV showed that the number of people taking at least five non-HIV medications was similar in the two groups (34% vs 39%). In the Multicenter AIDS Cohort Study, the numbers were flipped but the pattern remained the same (36.2% vs 30.0%).

At Zuckerberg San Francisco General Hospital, 74% of people with HIV were taking at least five non-HIV meds, and 48% were taking at least nine, said Cocohoba, who presented the data, along with suggestions for reducing polypharmacy, at ANAC.

We all know it's a problem.

All this polypharmacy can lead to poorer outcomes for patients, she explained. In the VA study, for instance, the more medications a patient took, the more likely they were to be hospitalized or to die. And in the San Francisco General study, 52% of the patients were taking at least one medication that met the American Geriatrics Society BEERS criteria for potentially inappropriate use.

Cocohoba is all too familiar with polypharmacy. As a pharmacist at the UCSF Women's HIV Program, she spends a lot of time trying to whittle down her patients' ever-growing drug lists and avoid medication errors.

She has waded through lists of statins and diabetes treatments, antidepressants, acid reducers, prescription blood pressure meds, and over-the-counter allergy pills, especially for aging patients, she reported, to say nothing of HIV drug regimens, which usually consist of at least three drugs.

"We all know it's a problem," she said. When a patient is on 10 or 20 medications, it is hard to know where to start.

Most of the time you don't start by reducing HIV meds, but the advent of highly effective two-drug regimens might change that, she added.

Two-Drug Options

In the SWORD 1 and SWORD 2 trials, 95% of participants who switched to the dolutegravir plus rilpivirine combination had suppressed viral loads 1 year out, as reported by Medscape Medical News. And in TANGO, the combination of dolutegravir plus lamivudine (Dovato, ViiV Healthcare) led to the same durable suppression as traditional three- and four-drug regimens at 48 weeks, as reported by Medscape Medical News.

"The pendulum is swinging," Cocohoba told the audience. "It was yes to three drugs and no to two drugs. And now it's yes to two drugs, potentially. There's actually some pretty good evidence coming out."

But immediately, Christopher Fox, RN, ANP-BC, from the Oregon Health and Science University in Portland, raised his hand and asked whether these drugs are being used at all in clinical practice.

"I think that there's a lot of nervousness that a lot of patients and providers feel about it," he said.

And he wasn't alone. Others in the room nodded, and Cocohoba acknowledged her own hesitation to monkey with effective regimens. Farley mentioned his patient with the inexplicable blips in his viral load.

There is a fear of the unknown. The studies look really good, but our patients weren't in the studies.

And Felicia Hall, RN, NP, from Mary Washington Healthcare in Fredericksburg, Virginia, described a patient of hers who moved from a three-drug regimen to the dolutegravir plus rilpivirine combination.

Although she is still virally suppressed, her CD4 count dropped from an average of more than 900 cells/mm³ to a number in the 500s. "She didn't want to stay on it," Hall told Medscape Medical News. "And yeah, she's undetectable. But if you're used to having a CD4 count of almost 1000, 500-something is uncomfortable."

And that's the crux, said Cocohoba. The process of changing medications is nerve-wracking.

A viral blip to 200 or 300 cells/mm³ isn't likely to confer resistance, she said. And a CD4 count of 500 cells/mm³ is enough to avoid opportunistic infections. Still, these are just anecdotes, with an N of two or three, and not enough to base clinical decision making on.

The conversation that was happening at ANAC is the same that Cocohoba is having with the care team in San Francisco. She's still moving ahead — she said she's going to move a patient to a two-drug regimen when she returns to the office — but changing real-life patients with multiple complex conditions to two-drug regimens is anxiety-provoking for both provider and patient.

"Although it's a great paradigm to be able to remove agents and potentially reduce toxicity, there is a fear of the unknown," she said. "The studies look really good, but our patients weren't in the studies."

Association of Nurses in AIDS Care 2019. Presented November 9, 2019.

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