What's the Next Game-Changer in HIV Treatment?

Dr. Gandhi is an associate professor of medicine at Harvard Medical School and the director of HIV clinical services and education at Massachusetts General Hospital.

I think long-acting drugs. I have still some patients who just find it very difficult to take a daily pill -- even once a day.

Researchers looked at the long-acting drug study [and] patients were asked about their satisfaction with their regimen. I thought it was very interesting that even people who are doing well on a pill felt like they were more satisfied with their treatment if they were getting six shots a year or a shot every month.

I have asked some patients. Personally, I've thought I would rather take a pill once a day than take a shot. But some of my patients have told me that if they could -- I've asked them in the context of PrEP [pre-exposure prophylaxis] also -- "Would you rather come in every two months for a shot or would you rather take a pill every day?" It's not scientific, but some people have told me they'd rather take a shot, even though I think of a shot as painful.

Photo courtesy of Rajesh Gandhi, M.D.

Dr. Grimsrud is the program specialist at the International AIDS Society.

I think it's going to be getting [treatment] into communities. We now have these fixed-dose combinations. You can take one pill, once a day, instead of six pills in a day. That really affords us the ability with viral load monitoring to move ART [antiretroviral therapy] delivery out into communities and out of health facilities. Patients don't need to come every month and be reminded that they have a chronic illness.

We've seen patient groups and implementers do it. We now also need the ministries of health to say, "We recognize the role of communities in supporting the rollout of treatment."

Credit: Warren Tong

Dr. Gallant is the medical director of specialty services at Southwest CARE Center.

The standard of care for initial therapy is still a combination of two nucleoside analogs ("nukes") plus a third agent. We haven't been able to get away from that approach for the last 20 years. But after multiple unsuccessful experiments with one- or two-drug regimens and "nuke-sparing" regimens, we may finally be getting closer.

For example, the combination of cabotegravir and rilpivirine [Edurant], both of which can be given as long-acting injections, looks promising in the LATTE-2 study. Even more impressive are the very preliminary data on dolutegravir [Tivicay, DTG] plus lamivudine [3TC, Epivir], which did well in a small 20-person study. It's too early to say whether this will be a game-changer because it may not work in larger trials. But if it does -- if this simple, well-tolerated two-drug regimen is as effective as standard-of-care regimens, with no resistance -- it will be hard to think of a reason not to use it.

Ironically, this comes at a time when our nukes are getting safer. Tenofovir alafenamide [TAF] appears to have all the advantages of tenofovir disoproxil fumarate [TDF] without the disadvantages of kidney and bone toxicity, so there's less motivation now to avoid nukes from a toxicity standpoint. But would no tenofovir be better than new-and-improved tenofovir? We'll have to wait and see.

Credit: MedPage Today via Joel Gallant.

Dr. Gandhi is a professor of medicine in the HIV/AIDS division at the University of California San Francisco.

The long-acting agents, hopefully co-formulated with other long-acting agents to treat comorbidities (or to provide hormonal contraceptives) when appropriate, for hopefully up to quarterly injections for the treatment of HIV.

Photo courtesy of Monica Gandhi, M.D., M.P.H.

Dr. Wohl is a professor of medicine in the Division of Infectious Diseases at the University of North Carolina and site leader of the University of North Carolina AIDS Clinical Trials Unit at Chapel Hill.

I think we've learned that we have to think strongly around things that work longer term. So I like the long-term drugs, I just think we have to be careful because we've heard many times, "take people who have a hard time taking medicines and give them a long-acting drug." And you know what? That may be in the history of bad ideas close to the top. Because you don't want to be at week 36 chasing down the guy who was supposed to be here at week 30 to get his shot, and he's got decreasing levels of rilpivirine and cabotegravir, and you're trying to find him. That's the worst-case scenario.

The guy who keeps up with his medication, who comes to every other appointment, that may not be the guy you want to give the long-acting drug, so you have to think about how to use these.

And if we're going to give it to people like that, we have to build up structures that allow that to happen. So we either have systems that go out and find those people and make it easier for them to come in, or we pay them to take their medicines. But I'm really worried about thinking that long-acting drugs are going to be the solution for the hard-to-reach populations.

Credit: Warren Tong

Dr. Althoff is an assistant professor at Johns Hopkins Bloomberg School of Public Health.

We know treatment works when used; the antiretrovirals are good at suppressing the virus. Innovative ways to identify individuals earlier in their HIV infection and get them into care and on treatment will be important. But once on treatment, lifestyle risk factors are likely to have a bigger impact on improving health outcomes among people living with HIV.

The emerging research is pretty clear: Modification of lifestyle risk factors is essential for healthy aging with HIV. Smoking cessation, alcohol and drug treatment, physical activity, weight management, addressing mental health needs and nutrition are all impacting how people with HIV age. It's more of a paradigm shift, from a focus on HIV treatment, to a focus on healthy aging with HIV.

Photo courtesy of Keri Althoff, Ph.D., M.P.H.

Mitchell is the executive director of AVAC.

I am very interested and looking forward to research on long-acting injectables for treatment. There are a lot of people who'd say, "But we know the drugs work. We know you can get virally suppressed. Why do we need a different formulation? We should just get more pills out."

But you talk to people who are living with HIV, taking pills for years -- decades even -- [and] the idea of maintenance therapy, where you might get an injection, could be really compelling. It could address a lot of barriers for people. So I'm interested in the science here -- but then it comes back to the first issue: Do people really want to go in every two months to get these injections? That's a question to be asked. I think that could be a huge game-changer in the foreseeable future.

Credit: Warren Tong

Laurel is the research director at Sero.

Leadership by people with HIV would be the game-changer: Actually trusting people with HIV and those from affected populations to help set the research agenda and to lead with community-based knowledge -- knowledge based in community experiences about what works to make it possible for people to live full, healthy, employed, stable, supported, lovely lives.

Credit: JD Davids

Dr. Berry is an assistant professor of medicine at the Johns Hopkins University School of Medicine.

Long-acting antiretrovirals. A friend of mine recently phrased this nicely. He said: "Look. If we're trying to get to 90% of people suppressed, that's great. It's a wonderful goal. We may well do it in the United States." But that means there's 10% of people who aren't. They're diagnosed; they might have been linked; maybe they're dropping out of care. But they're out there. We know it. There's 10% who aren't.

What do we do for that 10%? We're not going to forget that 10%; we can't forget that 10%. And my suspicion is that in going after that last 10% -- for which there are giant barriers for those people or otherwise they'd be suppressed -- I think actually long-acting formulations may be a very powerful solution for that.

So, it's not going to be the majority of people living with HIV. The majority of people living with HIV will be taking one pill, once a day and hopefully doing well with it and not having a lot of metabolic complications. But that 10% is tough. And there I think a potential game-changer is the long-acting antiretrovirals.

Credit: Myles Helfand

Dr. Scherzer is research statistician in the Department of Medicine at the University of California San Francisco.

What we're anticipating in kidney disease right now is the upcoming widespread use of TAF, which is the next-generation drug of tenofovir. TDF is the earlier version. The newer version is supposed to be less nephrotoxic. We know that from the clinical trials. But how is it going to play out in real-world cohorts? What's going to happen as a result of generic pricing for the old drug versus brand name?

What we're hoping here is that this is going to help inform the decision to switch. For example, if a patient seems to be doing well on TDF, the old tenofovir drug, should they be switched to TAF? Or can they continue? These early markers of kidney damage might be useful to inform that decision.

Credit: Warren Tong

David is director of research advocacy at Project Inform.

A lot of people get really excited about the possibility of long-acting treatment. And I do think that it's going to be a good solution for some people. But I also think that the enthusiasm might be a little bit premature.

One of the biggest things we struggle with is retention in care. Although a long-acting formulation might ensure coverage of a short treatment gap, it could lead to problems if there's a longer treatment gap because those treatments have a very long tail, and it could lead to the development of resistance.

Credit: JD Davids

Cindra is senior communications and policy advisor at AVAC.

I think what everyone's looking at is the long-acting injectables. But I think, more on an access issue, I really do think that community-controlled and -operated access is an issue. What you're seeing -- well, what we're hearing a lot from our partners in Africa is that they don't want to have to travel so far to access their care. And, again, they need culturally competent care, especially criminalized populations who are living with the highest burden: sex workers, LGBTQ, etc.

Credit: JD Davids

Miguel is director of AIDS.gov and senior communications advisor at the Office of HIV/AIDS and Infectious Disease Policy, U.S. Department of Health and Human Services.

One of the things that I'm so excited about is the fact that we are aggressively working to educate our community about one amazing tool in the response to AIDS, and that's PrEP. We have a hurdle to overcome because what we've talked about is two things. One is the number of health care providers who do not understand or are not aware of the benefits of PrEP. And two is, how do we make PrEP an understandable tool for an individual, make it a strong tool that we support and allow them to integrate it into their life in healthy and successful ways?

Credit: JD Davids