Promising drugs being developed at the UW could expand HIV treatment—if we get out of our own way.

by Vivian McCall

As Sidney Adjetey laid on an exam table at Harborview Medical Center with his T-shirt hiked up, research clinician Phoebe Bryson-Cahn examined injection sites on either side of his belly button. In April, University of Washington researchers at the UW Positive Research clinic injected Adjetey with about a teaspoon of a new and experimental long-acting HIV treatment as part of a study funded by the National Institutes of Health. They’re monitoring him to learn how long this medication lasts in his body and whether it could effectively suppress the HIV if the virus had been present.

Adjetey doesn’t have HIV, nor do any of the 12 participants in Phase I of this proof-of-concept clinical drug trial. At this early stage, researchers are evaluating dosing and safety because the drug has never been used on humans before. They’ll determine efficacy in Phase II, but that could be years away.

Injectables are a thrilling trend in the field of HIV, with drugs such as Lenacapavir and Cabenuva already available on the market. Unfortunately, the rollout has been slower than physicians hoped, and barriers like the expense of these drugs keep them out of reach for many. 

This new shot combines three commonly used oral medications into one lipid-bonded nanoparticle the researchers call a “nanolozenge.” A shot of the nanolozenges could theoretically keep HIV in check for a month or longer, replacing 30 to 90 daily pills.

Dr. Rodney Ho, the principal UW researcher who developed the drug and co-founded UW’s Targeted, Long-acting and Combination Antiretroviral Therapy Program, called it an “impossible marriage” of fat- and water-soluble drugs that took years to figure out.

Named for its oblong shape and diminutive size (roughly a million times smaller than a chicken egg), the lozenges are injected beneath the skin into a fatty area like the belly. Then they travel to the lymph nodes via the bloodstream. The lozenge analogy ends with their shape, though, because they don’t just dissolve. Instead, they journey through the lymphatic system like a city bus, stopping at nodes to drop off a specific concentration of antiretroviral drugs. 

This approach targets the virus far more efficiently than daily pills, which bathe our GI tract in medication and contribute to wear and tear. Scientists have successfully developed nanoparticle drugs to treat illnesses such as leukemia, but this experiment represents a new strategy for treating HIV.

The study’s leader, Dr. Rachel Bender Ignacio, said the researchers aim to formulate and bring to market a similar drug with three other compounds–tenofovir disoproxil, lamivudine, and dolutegravir, aka TLD, the most common frontline treatment of HIV in the world. She said that an injectable version of this drug cocktail could change the lives of the 19 million people already on TLD worldwide, which works out to almost half the number of people with HIV on Earth. 

Though we may see cheaper drugs in the near future there are a number of good reasons to create alternatives to pills. Some people with HIV struggle to get pills and to take the ones they’ve got. Unstable housing situations or addiction can stymie access, and some people may be too sick to swallow. Some agricultural and migrant workers can’t access a continuous stream of medication, and pharmacies may have trouble stocking them. A daily pill can be a painful reminder that you have HIV, and traveling with pills is a hassle, comes with stigma, and can be dangerous. Also, pill fatigue is real, and some people just forget.

Over time, skipping daily meds can be fatal. In February, study participant Adjetey’s half-sister in Ghana died from a bout of typhoid fever related to her HIV infection. Not taking viral suppressant medication weakened her immune system, and the fever killed her in two days. They weren’t close, but participating in the study gives him the opportunity to honor her memory, he said. 

Even if UW’s new approach works, Dr. Bender Ignacio said the fight against HIV/AIDS will never end. Viruses mutate, and HIV is particularly “leaky,” many times craftier and mutable than the flu or COVID-19. That said, from a biomedical standpoint doctors can easily treat HIV with current tools. Patients take two or three pills to prevent “breakthroughs.” Think of a medieval city with multiple defensive walls. If one falls, more remain. The walls are sturdy and in many ways sufficient. 

What we can’t seem to figure out is the human element: poverty, homelessness, individual behavior, geographical barriers, our convoluted medical system, etc. A miracle in the lab won’t undo systemic problems. Nine million of the 39 million people with HIV are not virologically suppressed. In the US, a third of people with HIV don’t have the medications they need, and they are often our society’s most vulnerable people. 

Dr. Monica Gandhi, who teaches medicine at University of California – San Francisco and who directs San Francisco’s “Ward 86” HIV clinic, said HIV treatment reached a point of stagnation six years ago after the advent of Biktarvy, a complete, once daily HIV regimen that included an integrase-inhibitor, which targets an enzyme HIV uses to replicate. It should be easy to take one pill, but it isn’t for everyone, and that’s why long-acting treatments are all clinicians like Dr. Gandhi can talk about now. 

She works with HIV-positive people experiencing homelessness in San Francisco. When Cabenuva first entered the market, clinicians hesitated to prescribe it to patients who took pills inconsistently. Doctors worried these patients would miss injection appointments and expose the HIV virus in their bodies to trailing levels of the medication, pushing the virus toward drug-resistant mutations.

But Dr. Gandhi’s patients showed up, and experiencing viral suppression for the first time motivated them to return. The clinic did not have to chase people down like they thought they might. Dr. Gandhi explained that because people with the highest viral loads are more likely to transmit HIV, treating them with the best drugs we have available should be a priority if we hope to end the epidemic. Now 290 people, or 10% of her clinic, are on long-acting medications.

The director of King County’s sexual health clinic Dr. Matthew Golden, said their unpublished randomized control trial also showed that injectables worked better than pills for patients facing homelessness, poverty, and drug-addiction. Golden said that incentives for study participants likely helped, and if we were smart, our public health system would offer benefits for regular treatment, too.

If UW’s drug ever hits the market, that goal could be even easier to achieve. UW’s shot has the potential to be cheaper and more widely available than any injectable we have now. If or when that happens depends on what researchers find in the lab and whether funders come along, cash in hand. Science is expensive.

The Stranger