Dr Rania Habib (Host): In 1981, an outbreak of rare opportunistic infections normally associated with immunocompromised people was identified in San Francisco and New York City in young men at an alarming rate. It took clinicians and researchers nearly two years to correctly identify the cause as human immunodeficiency virus, HIV, in the U.S. Infection rates in the U.S. continued to rise and death from complications of HIV and AIDS was often in the top 15 causes of death in the U.S. The CDC estimates that since 2013, the diagnosis rate for both HIV and AIDS in all 50 states has significantly decreased. There is still no cure for HIV or AIDS, so what has contributed to this decrease in overall disease?

This is Expert Insights with Carle Foundation Hospital. I'm your host, Dr. Rania Habib. Today's guest is Dr. Nassim Mokraoui, an infectious disease specialist at Carle BroMenn Medical Center. And he's here to give us an update on the advances in HIV/AIDS management, treatment, and research. Welcome, Dr. Mokraoui, and thank you so much for your time.

Dr Nassim Mokraoui: Hi. It's a pleasure to be here and thank you for having me.

Host: Many of our listeners may only have a vague understanding of HIV or AIDS. So, could you please provide us with a brief overview of HIV, the stages, and progression to AIDS?

Dr Nassim Mokraoui: So, HIV, very basically, it's a retroviral, it's a RNA virus. It gains entry into your immune system. And this is where it kind of gets tricky. The progression from infection towards the active disease can vary from weeks to months. Some of the symptoms people that start noticing it are, you know, constitutional symptoms, which is what we call it, where it's similar to kind of like the flu-like symptoms. You start feeling tired, you start having fevers, muscle aches, things like that, and it can progress to a variety of other issues. And a lot of these other issues are more about opportunistic infections or infections from other fungal or bacterial, which can cause other issues like GI issues, pulmonary issues. It can also cause neurological issues. Ultimately, it kind of depends on where the virus, first, I guess, wakes up and what it attacks first. Generally speaking, it's just this very prolonged stage of just not feeling well. And like I said, it could take weeks to months to years.

And HIV is diagnosed, generally speaking, by this antigen antibody testing. The more recent one, the fourth generation, came out fairly recently about 10 years ago, it's like very specific and sensitive. It really helps in detecting HIV, and the discrepancy between HIV and AIDS is predominantly based on the CD4 count. The lower the CD4 count means, that's when we use the distinction between HIV and AIDS. And not everybody with HIV presents with AIDS. Some people, their CD4 count is actually normal or lower than normal, but not meeting the criteria for AIDS. So, that's a distinction that we make when we first diagnose people with HIV.

Host: Okay. And what is the criteria for the designation of AIDS?

Dr Nassim Mokraoui: So generally speaking, if you were asking what the definition of AIDS, it's a CD4 count less than 200. It's what we use. Opportunistic infections can kind of help us determine the severity of AIDS. If we go below 200, we have different criteria and cut offs. And at lower levels, it's more about the opportunistic infections. Less than 200, we talk about PJP, which is a fungal infection which affects the lungs. It can be very devastating and cause a lot of respiratory issues. And then, as we get lower and lower, we start talking about other infections like toxoplasmosis. And then, we talk about mycobacterial infections or commonly known as MAC or MAI, which again also affects the lungs as well. And then, we get progressively lower and we get to the viral infection like CMV.

Those are generally the opportunistic infections or infections we look for or worried about. And it's also where we use the criteria of not just treating for HIV, but also giving antibiotics or antifungals to protect from these infections while you have AIDS.

Host: Now in my intro, I shared that the CDC reported a decrease in the overall diagnosis of both HIV and AIDS in the U.S. since 2013. Dr. Mokraoui, could you elaborate on the current trends in the U.S., what groups are currently most at risk, and what behaviors put people most at risk for contracting hIV?

Dr Nassim Mokraoui: We just had the IAS International AIDS Society Conference and they talked about it. And as an example, the CDC has a criteria that they want to meet by 2030, at the very least. And one country in particular, Australia has done a really good job following that model, which we use at CDC, they're 95, 95, 95%. It's diagnosed 95% of all HIV positive individuals and make sure that 95% of them are in antiretroviral therapy and achieve viral suppression of the 95% of those by 2030. And Australia right now is doing a fantastic job. They're at 90, 90, 90%, which is quite an accomplishment. We are behind and we're asking how we've made such improvements and strides in improvement.

I think one of the things that we've done is, I understand, the people that are at risk of getting HIV, people that engage in high risk sexual behavior, homosexuals predominantly, or transgender, those are the people. But we've also gotten better with testing as well. Our testing is over 95% sensitive and specific in detecting HIV. We've also done a better job with screening, not just necessarily people that are at high risk, we also offer screening for other individuals if they are concerned. We also provide testing in people that are at risk, like exposure, especially in a healthcare setting.

We offer early testing. So as an example, people that are sexually assaulted, they're always provided HIV testing, not necessarily because we think so, but we want to be sure. And if we want to go more specifically, pregnancy, we always make sure we know the HIV status of the mother so that if we know, we can treat the mother, get her under control so that there's no transmission to the baby.

I think there's more about awareness as well. The stigma is getting better about it. People understand it and they know to get tested for it just as a precaution.

Host: What groups are currently most at risk in the U.S. And what behaviors put people most at risk for contracting HIV?

Dr Nassim Mokraoui: At the moment, it's high risk sexual behavior, like homosexuals predominantly, or transgender people. Other people include sex workers as well. Less so IV drug users. It just depends on the circumstances for the IV drug users, whether or not they share needles with other people that have HIV or not.

Host: Dr. Mokraoui, if someone is actively engaging in some of these activities that put them at higher risk for contracting HIV, what is the current recommended testing protocol? I know you mentioned already the screening for mothers, et cetera, but what's the recommended testing protocol for the higher risk individuals and also those who are worried about the fact that they've contracted HIV.

Dr Nassim Mokraoui: One of the tests is just the HIV antigen antibody testing. For all patients, I know that it just depends on the type of person, whether they're sex workers or if they're involved in other activities like that or if they're just people engaging in high risk behavior. Initially, it's getting the testing if they have concerns about exposure, and that's the antigen antibody testing. However, if there's concern that the test may be a false negative, then getting a viral load will be the next go-to.

Host: As an infectious disease specialist, could you discuss the most common socioeconomic barriers that HIV patients face?

Dr Nassim Mokraoui: It's one of the most important parts of management of HIV patients, because unfortunately a lot of the patients that we deal with are in the lower socioeconomic portions of America. Some of them are homeless, some of them are poor, or some of them just don't have jobs at all, and it's a really important part and something that I really try to help with. Because the reality is that, if people are homeless, they don't have jobs, or they have other social circumstances that they kind of focus on.

They're less likely to be compliant with their medication, so it's a huge thing that we're dealing with, not just myself, but the society in general, is to try and take care of those, find them some sort of financial support, find them housing, anything like that, and it is a drastic difference. Like if you help them with that, their compliance generally gets alarmingly better and it makes you feel so much better. And then, you get the viral load under control, their CD4 count goes up, and so it makes them feel better.

Host: In 2012, pre-exposure prophylaxis, PrEP, was approved by the FDA. What is PrEP, and why was this considered to be such a milestone?

Dr Nassim Mokraoui: PrEP is a pre-exposure prophylaxis. The general idea behind it is taking this medication as a means of avoiding getting HIV from their high risk behavior. Generally, it's one medication depending on your preference and other issues with side effects or your past medical history. But it's a medication generally taken every day. There are certain circumstances where they have on demand PrEP. But generally speaking, it's just one medication you take. And it's been shown to reduce transmission. It's been kind of a godsend in a way. Basically, it's prevented transmission of HIV and it's actually helped meet the CDC's plans reducing HIV or transmission of HIV in the population. Part of it involves being seen in the clinic, taking the medication, but of course it requires testing every month with the provider, and it also requires explaining to the patients that taking PrEP only protects from HIV, but it does not protect from other STIs, and it is not a guarantee that you won't get HIV, but it is a really good medication in helping reducing the risk of obtaining it.

Host: That's fantastic. Now, for those who are not taking PrEP and are already diagnosed with HIV, Dr. Mokraoui, could you discuss the advances in HIV and AIDS treatments that have contributed to the fact that HIV patients are now living long, healthy lives with low virus loads?

Dr Nassim Mokraoui: So if we go back to the 1980s where we really didn't have any treatments, and it was a very difficult crisis, my mentor who taught me HIV, you know, who worked with me in fellowship, he dealt with HIV in the early stages, not the '80s, but he got to witness not just that, but also initially the pill burden and the side effects associated with these medications. I see some of these patients and they talk about it like you take so many pills that you can't eat because of how many pills you're taking or there were so many side effects that you would have to stop one medication or you didn't know which medication was causing it so it was very difficult and stressful.

So, you fast forward to now you have one pill, ideally, you take every day, and the side effects are so minimal, so low, people love it. You talk to patients in their 50s or 60s, and they'll tell you that relative to when they're diagnosed in the early 2000s, this is way better. The side effects are lower, they're easier to manage, the missing doses is a rare phenomenon for these people. And now, we're progressing to injectables. We're going to monthly injectables with a Cabanuva. And then, it makes things better, it makes it easier to manage. But I think the most important part is how effective these medications are, specifically with the introduction of integrase inhibitors, that was a landmark discovery, and adding this medication alone, that's really helped. It really is, as you talk about being so virally suppressed so quickly and helping maintain that suppression.

Host: Now, that's fantastic and thank you for sharing those advances. What are some promising updates and research for HIV and AIDS that we should expect, Dr. Mokraoui?

Dr Nassim Mokraoui: I mean, now we're trying to make strides into not just finding new treatments, because at the moment the treatments we have now work really well. We are making strides towards making injectables, which we already have, the Cabanuva, and we have Apretude for PrEP as well. But now, it's more towards vaccinations. I think that's the next hurdle that we're trying to accomplish.

And we have trials and, unfortunately, we haven't been able to find promise so far, and that's like one of the things. Treatments, it is more about trying to find long-acting medications that make it easier for patients. So, it's not once daily pills, but just injectables you get. So, it reduces the chances of non-compliance with the patients. Also, we're focusing now on pregnancy.

One of the things that's really promising is Biktarvy is being shown to be safe and efficacious in pregnant women, which is a huge improvement because we're going from two pills to one, which makes things easier for a pregnant population. But mostly, the research now, it's actually, like you said, socio-economic. It's how do we help them. What are the management strategies? How can we improve on that? What do we need to do to help them to prevent their non-compliance or issues at risk of getting further or worsening infections and resistance?

And lastly, we have now treatment options for highly resistant strains of HIV, which we still see on rare occasion. We have lenacapavir, which is a promising drug that's been shown to have efficacy with people that have highly resistant strains of HIV.

Host: Thank you for sharing those potential research and updates. It's fantastic. This has been such an enlightening session, Dr. Mokraoui. Are there any key take-home points that you would like to leave for our listeners?

Dr Nassim Mokraoui: If I think about the importance or why I do HIV or what I enjoy about it or what the importance of it is, like I said, it's to try to get the people that are at risk or at suspicion of HIV to be tested and treated. And for them to understand that there is a stigma, but the stigma's going away. It's not as bad as it was in the past. And to understand that there are treatments that work really well and with these treatments. It's not a cure, but you will live a normal life. Now, we're seeing people with HIV that are living normal lives, that we worry about the comorbidities of normal patient population, like heart disease, hypertension, their lipids, and things like that. They're able to continue relationships and not be worried about transmitting the infection once they're suppressed, because, you know, we have the saying undetectable, non-transmissible. So, it's been a huge improvement.

And so, to add to that, the important part of that is also having the social support involving family, your partners, your friends. It's really important to not try and hide the diagnosis or be ashamed of it, because having the support is also the important thing.

And then, the last thing is really want to stress is mental health. It's really important that their mental health is, managed, whether it's depression, anxiety. Because if the patient has issues like that, they're less likely to take their medication. And if it becomes a huge issue or problem, then we can offer them treatment to help with that. So, it gets them through and makes them take their medications.

Host: so much, Dr. Nassim Mokraoui. This was such an enlightening session.

Dr Nassim Mokraoui: Well, thank you for having me. It was a great pleasure and honor.

Host: For more information, and to get connected with one of our providers, please visit carle.org. Or for a listing of Carle providers, and to view Carle-sponsored educational activities, head on over to our website at carleconnect.com. I'm your host, Dr. Rania Habib, wishing you well. That wraps up this episode of Expert Insights with the Carle Foundation Hospital.