HIV Drugs in the Pipeline, Barriers to Patient Access

Monica Gandhi, MD, MPH, infectious disease doctor and director of the Center for AIDS Research at University of California–San Francisco, discusses how social determinants of health impact a patient’s ability to access HIV care and prevention, as well as drugs in the pipeline that could change the future of HIV treatment.

Can you discuss the unmet need in HIV care?

The HIV medications that we have had since 1996, which have been refined for the last 25 years, are amazing and work well. They have few toxicities and can be administered in one pill once a day. But there are still unmet needs in this population.

I happen to serve a very vulnerable patient population that is mostly not of public concern. There is a lot of substance use, mental illness, and, unfortunately, housing instability. Not everyone in the United States is doing well on HIV therapies because of the concomitant challenges in some of our patients' lives.

The same is true regarding preexposure prophylaxis (PrEP). PrEP has been approved by the US Food and Drug Administration (FDA) since 2012, but we still have profound discrepancies in adherence among those who use drugs, especially among racial and ethnic minorities.

One of the biggest unmet needs in HIV medicine is how to best serve vulnerable populations facing challenges due to social determinants of health. The long-acting HIV medications that are here already and incoming are extremely exciting in terms of the possibilities to address inequities in HIV care.

Like you just said, there are more treatments incoming. Regarding current research efforts, what are you most excited about?

We got our first long-acting injectable just six months ago. It was probably eclipsed by everything else going on in the world, but it was a huge advance. Cabetogravir and rilpivirine is a once-monthly regimen that can be administered intramuscularly.

Now, I want to talk about this treatment. The one concern with its approval and rollout is that its inclusion criteria for both the registrational trials required a relatively adherent population, as do the package inserts.

What I mean by that is the registrational trial with cabotegravir and rilpivirine required at least 16 weeks of being suppressed on an oral regimen. Now, there is a 4-week oral lead-in before we can administer the injectables.

What we do not have guidance on is how to use these injectables in poorly adherent patients, which are the populations that we are still struggling to treat. We are doing a pilot at Ward 86 to try to administer these injectables in patient populations that struggle with adherence.

There is so much coming up that I think could be a treatment possibility for these patients. I am most excited about the even longer-acting formulations.

We hope to someday treat people with once-every-six-months therapies, as with lenacapavir, which is the capsid inhibitor that is coming.

Then, we need to pair lenacapavir with something else, as we never do monotherapy for HIV. One possibility for combination therapy would be another new agent called islatravir. There is a possibility of administering them every three months or every six months together. We already have that formulation for lenacapavir.

Lenacapavir and islatravir are both being studied as preventative agents. Cabotegravir is already being assessed a preventative agent and has been filed with the FDA. It is an incredible time in HIV medicine. Even though COVID-19 set us back with some of our outcomes, the progress has been increasing.

Given this progress, where do you see the future of care going?

HIV care providers hope that we will one day be able to either administer treatment every six months by a subcutaneous injection, or prevention every six months in the same way.

There is also a possibility of a once-yearly preventative agent with islatravir. There is this dream shimmering on the horizon that we could give people islatravir as an implant once annually, and patients will have long-standing prevention for that entire year.

Anything that extends the interval between treatments for hard-to-reach patients makes it even more exciting. But it is imperative that long-acting medications are studied in hard-to-reach populations. That is my only worry.

What else would you like to add?

We had IDWeek 2021, which was a large conference with multiple abstracts about infectious disease and HIV. There was a very notable abstract, that I do not think surprised anyone, that showed how HIV outcomes have been set back by the global pandemic.

There are three ways in which it has been set back. One is lower rates of neurologic suppression—people not getting and taking their therapy. Another is the reduction in uptake of PrEP. The third is lower rates of routine HIV testing, which would reveal any new diagnoses.

Though COVID-19 is certainly not over, many of the infectious disease experts who worked on COVID-19 think that we need to shift our focus back to this chronic disease and reapply ourselves to the goals of HIV.

It is a particularly poignant year because it is the 40th anniversary of the first description of AIDS. I hope that people are shifting their mindset while commemorating HIV. We are certainly doing that in San Francisco because we saw our outcomes related to testing worsen.

About Dr Gandhi

Monica Gandhi, MD, is an infectious disease doctor and professor of medicine at the University of California–San Francisco (UCSF). She is also the director of the Center for AIDS Research and the medical director of San Francisco General Hospital HIV Clinic Ward 86, which serves local publicly insured patients.