Episode Transcript
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Tony: Hello and welcome back to another episode of Microbe Matters, presented by IDPITTStop, where we discuss, dissect, and demystify topics in Infectious Diseases with our experts here at UPMC and the University of Pittsburgh. I’m your host, Tony Morrison, media specialist here at Pitt ID and I’m just as curious as you may be about navigating through a world full of microscopic organisms. Please join us as we examine both the dangerous and beneficial microbial microcosms that surround us, promote public health, and showcase research and treatment of modern infectious diseases.
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Tony: Alex, a 28-year-old grad student in Pittsburgh, has always been careful. He’s done everything right. He gets tested regularly, talks openly with his doctor, and has been on PrEP for the last three years. It’s supposed to be nearly foolproof—one pill a day, over 99% effective at preventing HIV.
Tony: But then, a routine check-up brings unexpected news. The test comes back reactive. Positive. Alex is stunned. How? He never missed a dose. He did everything he was supposed to do. Yet, somehow, the virus found a way in.
Tony: Cases like Alex’s are rare, but they remind us that even the strongest defenses aren’t absolute. And when something unexpected happens, research is what helps us understand why.
Tony: At the forefront of this research is Dr. Urvi Parikh, an Associate Profesor of Medicine at the University of Pittsburgh, whose work bridges the fields of PrEP efficacy, drug resistance, and global implementation.
Tony: Her research tackles critical questions: How can we ensure equitable access to PrEP? What can rare cases of breakthrough infections teach us about HIV prevention? And what innovations lie ahead in the quest to end the HIV epidemic? Today, Dr. Parikh joins us to explore these pressing issues and discuss the future of HIV prevention.
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Tony: Hello, Dr. Parikh. Thank you so much for joining us today.
Dr. Parikh: Thanks. I'm really happy to be here.
Tony: Can you provide a brief overview of PrEP’s role in HIV prevention and your specific focus on implementation and your scientific research?
Dr. Parikh: Sure. Glad to. PrEP has been a game changer in reducing the number of HIV infections. PrEP can be more than 99% effective in people who use it. And the United States PrEP is currently available as a pill that you take every day or an injection containing the drug Cabotegravir that you get every other month.
Dr. Parikh: Globally, there's also a ring containing the antiviral drug delivery, and that women can use monthly to prevent HIV. PrEP is really good at preventing HIV infection. But despite how well PrEP works, sometimes someone gets HIV anyway. Our work focuses on gaining a better understanding of these breakthrough infections. We're kind of the whodunit mystery solvers for the rare infections that happen and people taking PrEP.
Tony: What are some of the most critical current issues in PrEP delivery and accessibility, both domestically and globally?
Dr. Parikh: It's so wonderful that we have these highly effective products that can prevent HIV, but PrEP can't work if the people who need PrEP can't get PrEP. So in the United States, health insurance approvals are a major barrier to accessing PrEP. We have a study called Zero PrEP, run by the University of California, San Francisco and the University of Pittsburgh, where we investigate breakthrough infections on PrEP.
Dr. Parikh: So let me tell you about a recent case who enrolled in our study. This person had been on oral PrEP, but then had to stop for 15 months due to loss of insurance coverage. They got back on PrEP, switching to injectable and stayed on it for over seven months. But then they lost insurance again for half a year.
Dr. Parikh: They were able to finally get back on PrEP again, but unfortunately got diagnosed with HIV only one month after restarting. Could this infection have been prevented? We can't know for sure, but the gaps in care certainly complicated the situation. Equity is another issue in the United States. The numbers I'm about to tell you are startling. In 2021 42% of new HIV diagnoses in the U.S. were in black adults, but only 14% of PrEP users were black.
Dr. Parikh: By contrast, about a quarter of new HIV diagnoses were in white adults, but 65% of PrEP users were white. Access to PrEP has been lower and communities of color. Clearly, we need to do better. There are different challenges globally. Injectable PrEP is now approved in over 50 countries, but in many settings can only be accessed through research projects and not from your health care provider.
Dr. Parikh: We're working on a project funded by PEPFAR through USAID called Mosaic, which is focused on accelerating introduction and scale up of new and emerging PrEP products across multiple countries. We hope to identify, understand and remove barriers to accessing PrEP, especially in adolescent girls and young women.
Tony: You mentioned rare cases of individuals contracting HIV despite adhering to PrEP. What are the key questions your team seeks to answer when such cases occur, and how might those answers shape future approaches to prevention and treatment?
Dr. Parikh: Through the Zero PrEP project in the US and the Mosaic project globally, we are interested in characterizing infections that happen in people taking PrEP. How did they get HIV on PrEP? Is it because they didn't have enough PrEP in their body to prevent infection? Did HIV develop mutations against the PrEP drug?
Dr. Parikh: Even more curious is why PrEP doesn't work in rare cases of people who get on time injections. We recently reported on three new cases of HIV infection in the US who enrolled into Zero PrEP. All three are HIV, even though they had on-time PrEP injections for many months. We found that two of these cases had low levels of drug resistance that is related to the PrEP drug they were taking.
Dr. Parikh: We're continuing to investigate these findings to understand if low levels of drug resistance could impact future treatment for HIV.
Tony: What are your findings on drug resistance, and what are its implications for future treatment and prevention practices for HIV?
Dr. Parikh: Drug resistance to HIV medications is a risk for people who become HIV infected while taking PrEP, but drug resistance will be limited to the class of drugs taken for PrEP.
Dr. Parikh: For example, injectable PrEP with Cabotegravir is in a class called integrase strand transfer inhibitors, known as insti. Drug resistance that occurs with cabotegravir PrEP could make and instis used for treatment less effective. The good news, though, is that we have so many treatment options available in the US that living a long and healthy life with HIV, even after getting infected on PrEP is still possible.
Dr. Parikh: We followed up on the Zero PrEP cases that I told you about, and I'm glad to report that all of them started treatment and are doing very well and have achieved viral suppression on their medications. Up to six months after being diagnosed with HIV. Our research on drug resistance and treatment outcomes after getting HIV on PrEP is especially important globally, where there are fewer drugs available.
Dr. Parikh: It will be important to investigate whether people who get HIV on PrEP can use the most common first line treatments.
Tony: What unique challenges arise in monitoring PrEP efficacy and HIV prevention domestically compared to places like sub-Saharan Africa?
Dr. Parikh: One of the biggest disparities is the access to lab tests. In the US., PrEP users are tested for HIV routinely using sensitive, laboratory based tests that can detect the virus directly.
Dr. Parikh: If they do get infected. Their virus can be sequenced to look for drug resistance mutations, and treatment for HIV can be customized. In many countries, HIV testing is done using rapid tests that look for the body's antibody response to the virus, which can take six or more weeks to detect. For PrEP users, the antibody response can be delayed even further.
Dr. Parikh: Drug resistance testing is also not routinely available. Through our Mosaic study, we are working with Ministries of Health in multiple countries in Africa to set up drug resistance monitoring for people who acquire HIV on PrEP. The same drugs and drug classes are being used for both HIV treatment and prevention.
Dr. Parikh: The findings from our studies will help countries optimize PrEP, rollout and set guidelines for best use of HIV medications for both PrEP and treatment.
Tony: We’ve seen significant advancements in PrEP, such as long-acting injectables and multi-purpose prevention technologies. Looking ahead, what are some of the most promising technologies or approaches being developed in HIV prevention?
Dr. Parikh: Here are my top three most exciting advances in PrEP. So first, Lenacapovir is an injection that you get every six months. Imagine being able to get one shot that can prevent HIV infection, then not having to think about it for a half a year. Clinical trial findings have been really promising, and there's a lot of hope for this new product being approved in the near future.
Dr. Parikh: People are also working on new formulations where drugs are loaded into films, patches, implants for safe and reversible slow-release delivery. These are cool because unlike a shot that stays in your system, these devices can potentially be removed if HIV prevention is no longer needed. Finally, combining PrEP with other medications like for contraception, STD prevention, and a one-stop-shop would be convenient for users and could make a huge positive impact for people dealing with multiple health concerns.
Dr. Parikh: It could help people meet many of these needs at once, rather than having to prioritize one over the other.
Tony: And how does your work help to contribute to these efforts?
Dr. Parikh: So in addition to the implementation studies we work on, our lab does experiments using cultured cells and tissues to see how protective these new products may be against HIV.
Dr. Parikh: These early lab studies are important for new product development.
Tony: How do these innovations fit into the broader goals of ending the HIV epidemic?
Dr. Parikh: Some people may say, “hey, we already have these amazing products that prevent HIV. So why do we need more?” It's important to recognize that PrEP is not a one-size-fits-all solution. A pill a day won't work for someone who has a hard time remembering to take it or could put themselves at risk if someone discover the prescription bottle.
Dr. Parikh: Injections could be ideal for some people and difficult for others if they can't make it to their health provider every two months. Choice is important, and the more options we have, the more likely it is that one of those options will be best for the person who needs it most.
Tony: What gives you hope for the future of HIV prevention, particularly in terms of making it more accessible and effective globally?
Dr. Parikh: I think we've made so much progress in the area of community engagement and thinking about PrEP as something that can fit into someone's healthy lifestyle, and not just a medication needed to prevent a disease. There are so many new hip ad campaigns and supportive services being developed to help people start and stay on PrEP. So, for example, in the Mosaic project, the Next-Gen Squad is a group of dynamic young women under 30 from countries in Africa who are advocating for young people's needs, preferences and lived experiences to help meaningfully shape the research being done on PrEP.
Dr. Parikh: Their enthusiasm and engagement is inspiring and will help expand PrEP's reach to the women that carry some of the greatest burden of HIV infection. To me, seeing people becoming empowered to make their own choices about HIV prevention gives me a lot of hope.
Tony: If you could highlight one critical next step that the scientific community or global policymakers should take to accelerate progress, what would it be?
Dr. Parikh: So access to PrEP globally is a critical and urgent need. It's hard to highlight just one thing, but here are a few that I think we need to keep working on. One is that the US President's Emergency Fund for Aids relief, known as PEPFAR, needs to continue to be funded so we can keep up the fight against HIV globally.
Dr. Parikh: I cannot emphasize enough how transformative PEPFAR’s work has been for reducing the devastating burden HIV has had on countries. We have come so far, but are not at the finish line yet, and now is not the time to quit this work. The companies that produce PrEP drugs need to have enough supply available and distributed to the countries that need it.
Dr. Parikh: And as researchers, we need to keep developing new, effective products that people will desire and will fit well in their lives for HIV prevention. For me personally, I will keep working to understand HIV infection on PrEP and the impact of HIV drug resistance, with the hope that this knowledge can help preserve the drugs we have for both prevention and treatment.
Tony: What message would you like to share with young researchers, healthcare providers, and even communities about the future of HIV prevention and treatment?
Dr. Parikh: I want to say that we're in a really exciting moment in the field of HIV prevention. There are so many great options available now, and we must continue to the work to create new technologies for PrEP that will take users preferences, most importantly, their desires and their needs into account.
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Dr. Parikh: I see a bright future and much progress towards ending the HIV epidemic here in the US and globally.
Tony: Dr. Parikh, this has been an enlightening discussion. Thank you for sharing your expertise and helping us understand where the future of HIV prevention is headed.
Dr. Parikh: Thanks so much, it was a pleasure to speak with you, and I hope that our listeners are also excited and enthusiastic to join this fight against HIV and keep the work going.
Tony: As we continue our journey through the ever-evolving landscape of infectious diseases, conversations like this remind us that scientific progress isn’t just about discovery—it’s about ensuring that innovation reaches those who need it most.
Tony: Join us next time on Microbe Matters as we explore more groundbreaking work in infectious diseases, bringing research from the lab to the community and beyond.
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Tony: Thanks for listening! If you’d enjoyed this episode, make sure to subscribe to the show wherever you listen to podcasts, and be sure to check us out on social media at IDPittStop.
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