One-A-Day Wonder

Drug resistance is a growing problem for people living with HIV. As antiretroviral medications have extended the lives of HIV-positive people and turned living with the virus into a manageable chronic condition, it has meant more poz folks are taking drugs for longer periods. Current HIV regimens involve taking daily medication (longer lasting treatments are in the works), something that is difficult for anyone to adhere to seven days a week for years or even decades at a time—without missing a dose or two.

Combined, these truths are a recipe for the development of drug resistance. Particularly when there are breaks in treatment, the virus is able to mutate, and it can develop genetic immunities to particular classes of drugs (which all share a common method of attack).

“Despite significant progress, clinical challenges remain in the management of HIV [as it is] related to adherence and the risk of developing HIV drug resistance,” Kimberley Brown, a medical director at Janssen Scientific Affairs, a pharmaceutical company of Johnson & Johnson, tells Plus. “In the treatment of HIV, adherence is critical, because missing just a few doses can lead to drug resistance, which can stop a person’s medication from working. However, people living with HIV often miss doses of their treatment due to a variety of factors, including pill burden, convenience, stigma, and tolerability of therapy over time.”

Resistance is a significant concern, but so too is the fear that taking some HIV medications long-term may be detrimental to poz folks in other ways. Some of the worst side effects from combination drug therapies can include bone density and kidney-related problems. The end goal is to come up with new treatments that minimize these problems. Earlier this year, at the annual Conference on Retrovirues and Opportunistic Infections, researchers unveiled further positive results from Phase 3 trials of a new once-daily, single-tablet regimen from Janssen that hopes to do just that.

Submitted to the U.S. Food and Drug Administration for approval last year, Brown says, darunavir, cobicistat, emtricitabine, and tenofovir alafenamide (D/C/F/TAF) is currently under review.

“If approved in the U.S.,” Brown explained, “D/C/F/TAF could give clinicians a simplified treatment option that offers the benefit of a once-daily [single-tablet regimen] with the durability and high barrier to resistance of darunavir coupled with the bone and renal safety profile of TAF for those living with HIV who may be at risk for drug resistance.”

The application was filed for the treatment of HIV-1 in adults and pediatric patients ages 12 and older and was based on the results from the ongoing EMERALD and AMBER Phase 3 trials, which Brown says “demonstrate the potential of D/C/F/TAF as an important treatment option for a wide range of patients regardless of previous treatment history, including those with previous virologic failure, experience with multiple [antiretrovirals], and in some cases, unknown baseline [resistance-associated mutations] to agents other than study drugs.”

Those are important distinctions, since many new HIV treatments unveiled in the past few years have been specifically for those who had never been on HIV treatment before. That’s been a boon for those just diagnosed with HIV, but those who’ve experienced treatment failures—particularly due to developing resistance to multiple antiretroviral medications­—
haven’t gotten a lot of new options.

Previous findings already suggested D/C/F/TAF offers new hope for those facing drug resistance or concerned about kidney issues. Brown says the latest “analyses presented at CROI are consistent with the pivotal data previously presented and are relevant to the real-life clinical challenges physicians face in treating diverse patients with various levels of treatment experience.”

If approved, the drug would be the only complete regimen delivering the benefit of a once-daily single-pill HIV cocktail with darunavir, a drug that has proven to be less at risk for the development of drug resistance, and tenofovir alafenamide, which has been less detrimental to kidneys and bone density than other HIV drugs.

EMERALD has been examining whether people whose HIV is already under control with the help of antiretroviral medication could switch to the new drug without negative consequences. Brown says one of the things that makes the study unique is the number of participants who had resistances to multiple drugs (and thus are in most need of finding a new regimen to switch to).

“Unlike other HIV switch studies,” Brown says, “EMERALD had more inclusive entry criteria and may be more representative of the treatment-experienced patients in clinical practice since the study included patients with previous non-darunavir virologic failure, prior experience with multiple antiretroviral and known baseline resistance-associated mutations to agents other than study drugs. Yet, we saw high response rates and low rebound rates in both our pivotal trials, even with these more inclusive criteria.”

These analyses demonstrate the potential of the drug as an important treatment option for patients regardless of previous treatment history. It could receive FDA approval later this year.