This content originally appeared on thebodypro.com. View the article here.

Key Takeaways

• Funding withdrawal, not scientific failure, has shuttered pre-exposure prophylaxis (PrEP) programs and put the brakes on prevention research, according to Raphael Landovitz, M.D., M.Sc.
• Weekly oral lenacapavir’s regulatory submission adds to a widening menu of daily, on-demand, and long-acting PrEP options.
• We continue to see evolving expert opinion on HIV testing recommendations and time to protection for cisgender women.

Raphael J. Landovitz, M.D., M.Sc., gave a compelling plenary at the recent 26th International AIDS Conference (AIDS 2026), outlining how the science of PrEP continues to evolve and the risk that those advances will be reversed by political decisions. Speaking with TheBodyPro the following day, he expanded on what that means for clinical practice.

Landovitz is a professor of medicine and the chief of the division of infectious diseases at the University of California Los Angeles. He is also one of the principal investigators of the HIV Prevention Trials Network. His research focuses on optimizing antiretroviral therapies for HIV treatment and prevention, especially long-acting and extended-release products and delivery systems for HIV and STI prevention. This transcript has been edited for length and clarity.

Terri Wilder, M.S.W.: You began your plenary by telling the audience you’d changed the title of your talk. It was listed as “PrEP 2026: State of the ART,” and you changed it to “PrEP Works: The Challenge Is No Longer Scientific.” Why?

Raphael J. Landovitz, M.D., M.Sc.: I don’t think you can give a talk about HIV in 2026 without acknowledging the reality of where we are. There have been tremendous biomedical and programmatic advances over the last 40 years of the epidemic, particularly in the last 15 in the prevention space—and they are all horribly, frighteningly at risk of being reversed because of cuts in funding. It would be an exercise in absurdity not to acknowledge that up front. So I changed the framing: The title they gave me was a little vanilla, and this is not a vanilla time.

Wilder: One of your strongest messages was that we don’t have a scientific failure but a political failure. You cited unprecedented cuts to HIV-related research—can you talk about the consequences of those cuts?

Landovitz: I’ll answer with two concrete examples. We have these extraordinary results from the PURPOSE studies, with near-elimination of incident HIV in people on every-six-month subcutaneous injectable lenacapavir. There were plans to scale up access and distribution, but they were all predicated on an infrastructure we thought was secure. PEPFAR had been funded in a politically agnostic way since [former President] George W. Bush started it. Everyone imagined that at some point there would be local ownership of programs, but nobody anticipated a complete switch-off of U.S. support. Scaling up this prevention intervention depended largely on that infrastructure. When it was withdrawn, treatment and prevention programs began shuttering overnight, and one of our most transformative prevention options was left with no platform to reach the people who need it.

The second example is in the research space. Take Sharon Hillier’s MATRIX program, which was funded by USAID. Her program had people with investigational vaginal rings in their bodies, testing a new prevention product, and the funding was cut off so abruptly that there was no immediate mechanism for investigators to even see these participants—who had signed informed consent—to remove an investigational device from their bodies. We have an ethical obligation to protect the safety of people who trust us and participate in our research. The U.S. government was funding this and made these cuts without taking responsibility for the safety of these participants.

There are a number of examples like this; that’s one of the most dramatic. How do you ever regain the trust of a community and say, “We believe our funding is stable enough to complete this work—trust us”? It is horribly distressing, on a humanitarian level, on an ethical level, and for the future of the advancement of science.

Wilder: Let’s talk about event-driven, or on-demand, PrEP. Can you tell us about the SimpPrEP trial in France and Thailand, and the gaps you think it will help fill?

Landovitz: For some reason, this trial has flown a little under the radar. SimpPrEP is sponsored by the ANRS, the national HIV clinical trials group in France, and is led by Jean-Michel Molina—who many people in the field know from the original IPERGAY study, his work on doxyPEP, and other HIV and STI treatment studies. It uses TAF/FTC (Descovy) in a one-dose pre-coital, one-dose post-coital regimen, as opposed to the 2-1-1 regimen we’re used to using with TDF/FTC (Truvada). That’s based on the way TAF/FTC behaves pharmacokinetically in peripheral blood mononuclear cells, or PBMCs: A single dose afterward gives you the same exposure as two daily doses of TDF in the 2-1-1 regimen, so you may not need a double dose up front because TAF concentrates more quickly and better in PBMCs than TDF does.

SimpPrEP is only with [men who have sex with men (MSM)], but the bigger thing that’s evolving in our thinking is related to the role of PBMCs. We originally thought tissue concentrations in the genital tract were an important driving factor in the differential trial results for vaginal versus rectal exposures in the early PrEP trials. But there was a very provocative paper recently in Nature Communications by Sara Iannuzzi and colleagues that reanalyzes all the data for MSM, and finds that the trial results correlate best with what’s happening in PBMCs, and much less with tissue concentrations. PBMC pharmacokinetics don’t differ on the basis of sex at birth, nor on the use of gender-affirming hormone therapy. So if it’s true—at least for tenofovir-based PrEP, and this may not hold across agents—that activity is best predicted by what’s happening in PBMCs, then what works in one population should work just as well in another.

Wilder: For clinicians who care for cisgender women, I’m wondering if you can talk about practical guidance about when PrEP protection begins after initiation, and how to counsel their patients?

Landovitz: This is one of the more controversial topics. The more PrEP researchers you ask, the more answers you’ll get, and I’m willing to bet some would come to fisticuffs. But I’ll tell you what I think.

At the very beginning, the [U.S. Centers for Disease Control and Prevention (CDC)] said something that was quite extreme—estimating 21 days to protection in the female genital tract. Our thinking evolved, and more recently people landed on something more like seven days, which is what the IAS-USA guidelines now say. But the more I think about it—particularly with the idea that PBMCs are the relevant matrix for tenofovir-based PrEP—I don’t see a reason why protection should differ for vaginal versus rectal exposure; what protects against one should protect against the other.

That has real dosing implications. A couple of years ago, the British guidelines made a first-of-its-kind recommendation that people with vaginal exposures could use peri-coital dosing—but with a double dose up front and a dose every day for seven days after the last exposure, which would be quite cumbersome. I’ve had some robust conversations with people on that guidelines panel; it was an absolutely rational and carefully considered (and groundbreaking) recommendation at the time. But with the new data and analyses, I wonder whether they’d reach the same conclusion today. I would not be surprised to see recommendations harmonize toward 2-1-1 regardless of route of sexual exposure, for people who aren’t willing or able to take a more regular or clinically proven regimen.

I want to be very clear, though: This is all based on PK/PD modeling, and we need clinical evidence.

Wilder: In the pipeline part of your talk, you discussed weekly oral lenacapavir, recently submitted for regulatory approval in the U.S. You said it wasn’t “on your 2026 bingo card.” Tell us more.

Landovitz: I didn’t expect this at all. You’ll remember that in late 2021, injectable lenacapavir went on a [U.S. Food and Drug Administration (FDA)] clinical hold because of complications from the borosilicate vials it was stored in. It got repackaged in a different glass—aluminosilicate—and the trials continued. What I didn’t realize, since I wasn’t an investigator on any lenacapavir trials, is that during the period when the injectable product wasn’t available, they bridged people with 300 milligrams of weekly oral lenacapavir, based on PK modeling. So we now have actual clinical data from that interruption period on what concentrations weekly oral dosing generates in humans—both in people with HIV and people taking it for PrEP. That experience from the HIV treatment studies was recently published in AIDS.

On top of that, the PURPOSE registrational trials were amended midstream so that if someone was more than two weeks late for a six-month injection, they could bridge with weekly oral lenacapavir, and the open-label extensions allowed the same. So that may be an additional data set that informed the regulatory submission.

I did not imagine that we would see a regulatory submission for weekly LEN for PrEP, but soon we’re going to have injectables that are every two months or every six months, and oral products that are daily, on-demand, maybe weekly, maybe monthly. As this menu of choice expands, it’s only exciting from my standpoint.

Wilder: Let’s talk about HIV testing. You described it as an area where the pendulum continues to swing. Where is the field headed on testing before and during PrEP use?

Landovitz: One reason I’m so passionate about this is that I feel like I was part of the problem. When we conducted HPTN 083, we observed that with a potent long-acting antiviral, conventional HIV testing algorithms—antigen/antibody-based rapid and lab tests—masked rare breakthrough infections on cabotegravir. When we went back and tested stored specimens, we could find these infections earlier by detecting RNA at earlier time points. That mattered because the longer a masked infection percolated, the more integrase resistance accumulated, which could compromise treatment options. So detecting it earlier, before those mutations emerged, ended up in the FDA label for cabotegravir, and the 2021 CDC guidance recommended RNA testing as part of the algorithm.

A lot of people immediately said that was crazy—too expensive, not widely available, never going to be globally scalable. And in fact, when we implemented RNA screening prospectively in the open-label extension of HPTN 083—everything I just described was retrospective—it performed terribly. Nine out of every 10 positive RNAs, when nothing else was positive, were false positives. You can imagine the psychological distress, the cost, and the time it took to sort that out.

My thinking has really evolved. In fact, the best way to figure out whether a lone positive RNA is real or false is to bring the person back and retest—but by the time you’ve done that, you’ve often lost the ability to avoid integrase resistance anyway. So the original motivation is probably not really able to be fixed with RNA testing after all.

You might ask, aren’t there other reasons to diagnose someone early—transmission to partners, risk to their own health? But in these cases the viral load is so low that there should not be any risk of sexual transmission. Blood supply or parenteral transmission may be a different question—I still worry about that. And there’s unlikely to be immune damage at those low viral loads, in the short term. Minimizing the reservoir size may be an additional motivation for early detection—this is still being studied, and is a fascinating topic in and of itself. But from a public health standpoint, any time you delay initiating or redosing PrEP, you put a person in a position of vulnerability to HIV acquisition. On balance, we should use the best locally available testing algorithm at initiation and follow-up, and that should not be a barrier to prescribing or re-prescribing PrEP. That’s where my pendulum has swung. I feel like our observations sent the field spiraling in this direction, and I’m trying to course-correct.

Wilder: You made a call to action on new diagnostics.

Landovitz: It would be great if we had more sensitive diagnostics that were cheap, durably supply-chained, and point-of-care. We developed COVID tests in a heartbeat. Where is the impetus to make the same kind of rapid progress here? There are regulatory hurdles, which were relaxed in the COVID context because we were in a global pandemic. I just want to remind people: We’re still in a global pandemic, and we have been for 40 years.

Wilder: You ended your plenary by saying that the people in power will never see the faces of those who will pay for those harmful funding decisions. That hit me in the gut—these are real human beings, people who came to our clinics, people who are part of the communities we serve. Sometimes clinicians don’t think of themselves as advocates or activists. What is one thing you want clinicians to do, or to think about, regarding their role in this political climate?

Landovitz: Different people have different levels of comfort with public statements or public activism. But defiance can, in and of itself, be an act of resistance. This work, this patient care, these programs, this research are things that are too important to let them fail at the hands of politicians. Simply persisting—with exquisite clinical care, with asking the difficult research questions, with leveraging every remaining resource to provide equitable care—is an act of activism and resistance. People don’t need to be marching in the streets or signing letters. Just continuing your work doggedly, despite all these obstacles and affronts and chaos and distractions—that is activism.