Injecting HIV drugs every month or two is as effective in suppressing the virus as taking daily medications, according to an eight-month clinical trial conducted by ViiV Healthcare and Janssen Sciences Ireland. It could also improve adherence rates by reducing the potential of skipped doses.
“Going from many pills a day — like 10, 20 pills a day — to now one pill to now one injection every two months is, I think, a huge medical technical achievement,” said Paul Stoffels, chairman of pharmaceuticals for Johnson & Johnson, which is Janssen’s parent company. “Despite great progress in HIV treatments, the burden of treating HIV patients remains high. Long-acting injectable drug formulations may offer another option for HIV maintenance therapy.”
Just 32 weeks into the 96-week phase IIb trial, known as LATTE 2, researchers were so impressed with results they announced them to the press. The study compared a long-acting injectable combination of two separate drugs (cabotegravir and rilpivirine) with a three-drug daily pill regimen (cabotegravir paired with two nucleoside reverse transcriptase inhibitors).
Once HIV enters T4 white blood cells, the virus uses an enzyme called reverse transcriptase to copy parts of its RNA into the cell’s human DNA via a process called “reverse transcription.” Rilpivirine blocks that process by binding to and blocking the enzyme. Meanwhile, cabotegravir attacks HIV at another point in the virus’s life cycle. After the virus transcribes its RNA into DNA, it then must integrate that DNA into the white blood cell’s DNA. It does this with the help of another enzyme, integrase, which cabotegravir blocks from doing its job.
Participants in the clinical trials were either virally suppressed on antiretroviral therapy or were HIV-positive and not previously on medication. After reaching virologic suppression on oral therapy, the patients were subsequently randomized to one of three studies to receive either the injections every four or eight weeks or continue on oral treatments.
Regardless of frequency of the shots, patients receiving intramuscular injections of the long-acting formulation had viral suppression rates comparable with daily combination therapy. Patients on monthly injections reported more pain at the injection site than those receiving the shots every two months. This pain was the most commonly reported side effect, leading a minority of study participants to withdraw due to “injection intolerance.”
John C. Pottage Jr., ViiV Healthcare’s chief medical officer, focused on the trial’s positives, saying, “These initial phase IIb data investigating long-acting cabotegravir and rilpivirine are promising and build on the results we have seen to date. We look forward to seeing further results as we move into phase III.”
As currently formulated, the drug must be refrigerated and would need to be administered by a medical professional as it requires too large a dose to be prescribed for at-home injections.
Stoffels acknowledged that there is still work to be done. But the executive highlighted how far the pharmaceutical fight against HIV has come since he began his career in Africa, recalling that “back in the late ’80s in Africa, when the HIV epidemic was in full growth, it was devastating.”
It may be another five years until it’s available, but an injectable, monthly HIV treatment could free people living with HIV from an endless regimen of daily pills, while reducing treatment fatigue and increasing adherence. That’s a win-win situation to many.