Viremic – Cases in HIV

Announcer:
Welcome to Viremic–Cases in HIV, hosted by Dr. Eileen Scully and Dr. Christopher Hoffmann, both HIV specialists at Johns Hopkins, who explore quandaries in adult HIV care. Each case discussion includes medical history and diagnoses, challenges in care and treatment, and key evidence and guidelines that inform clinical decision making.

Cases are presented as a composite from the hosts’ clinical practice, with all identifying details removed to protect the privacy of patients. Case discussions are for informational purposes only and not offered as medical or clinical practice advice for patients or clinicians. Any mention of specific medications or commercially available products is a description of use only, not an endorsement.

Dr. Eileen Scully:
Welcome to Viremic. I’m Eileen Scully, coming to you from Johns Hopkins, and I’m joined today by my friend and colleague Dr. Chris Hoffman. Before we start, if you like this podcast, please share it with a colleague and follow us wherever you access podcasts. In addition, we love hearing from listeners. Please send questions or future topic suggestions to us at viremicpodcast@JH.edu. Chris, it’s great to be with you again today.

Dr. Chris Hoffmann:
Thanks, Eileen. Likewise.

Eileen:
Today we’re going to start with another one of our theoretical cases. This is a 48-year-old man who has HIV that is well-controlled on dolutegravir/3TC [lamivudine]. He has previously been sexually active and used apps mostly to find partners, which allowed indication of HIV status, and he always identified as positive and felt like that was adequate disclosure and did risk mitigation by using that sort of self-identification in terms of onward transmission. More recently, he’s met someone and they are starting to date. His partner is not HIV-seropositive, and they have not yet been sexually active. This is sort of new territory for your patient. It’s a growing relationship and one that feels different than prior sexual partnerships.

Your patient wants to know if there are ways to limit the risk of HIV acquisition for his new partner who is not currently on PrEP [pre-exposure prophylaxis] and hasn’t been overwhelmingly interested in this [PrEP]. Chris, before we get into a discussion on methods for prevention of transmission, could you talk a little bit about what you explore with a patient when talking about HIV disclosure status and partner status and how they approach partnerships in general?

Chris:
Great question and something that comes up commonly, in my practice at least, where patients ask me about navigating a new relationship. Sometimes it’s around HIV specifically and sometimes it’s more around general health and relationship issues. In terms of the HIV specifically, my starting point for all my HIV care is to try to normalize living with HIV, including that somebody living with HIV can have a full and romantic sexual life.

I sometimes ask patients if they’re happy with their sex life, when I first meet them and at other visits. I ask this partially to open discussion about topics a patient may be hesitant to raise around sexual questions, but even more to reinforce that HIV shouldn’t interfere with a desirable sex and romantic life. I think it’s applicable to this patient who has a new romantic interest and potential sexual partner.

Eileen:
I love that question about “Are you happy with your sex life?” I was at a conference recently where one of the presentations, led by a community advocate, was talking about how infrequently physicians address the question of sexual satisfaction. What a great way to open up a discussion about this. I do something similar. I ask people, including my well-established patients, if they’ve been sexually active. And if they say no for any reason, I always ask them, “Why not?” because coming from a place of assuming that that would be normal, healthy, and expected allows people to be more open about it. I often add in some sort of half-joking reference to there being not enough good candidates, which many people respond to quite well. But again, I love this idea of opening the conversation with normalizing that sexual activity is part of the human experience.

Chris:
Anything to get a patient talking about sex and sexual questions is so important in healthcare overall, primary care, but especially in the world of HIV care. Going further, I really try to call out what is normal and what is not normal about living with HIV. Perhaps what isn’t normal is having to be on a medication for life. Pretty much everything else can be normal. With effective antiretroviral therapy, people can live essentially the same length of life as somebody without HIV. Most comorbidities are similar, with exceptions and some additional screening and assessments over the life course of an individual. The rest of life, whether it’s exercising, work, employment, education, relationships, sex, friendships, travel, all of those should be fulfilled in a way they would fulfill them if they were not living with HIV. I try to work through that with patients and help them understand that. Sometimes there [are] phobias, challenges, internalized stigma, guilt, shame, and I don’t get through fully to somebody, and I refer them to a clinical psychologist or other therapist to further those discussions, so that somebody can reshape a positive self-image that does not start with their [HIV] diagnosis.

Eileen:
Chris, I think you’ve brought us right to the heart of the question for this patient, which is this idea that, even in the context of being a person who carries HIV, you can have what would be considered a totally normal sex and relationship life. We should be clear here that that has not always been true, that prior to the advent of suppressive antiretroviral therapy, there were additional considerations that people living with HIV took on as a burden in terms of preventing onward transmission. But that’s not where we are now, and I think that’s a major point of education. So, I’ll add a little more data and we can turn back to our patient and get into what we mean by that. He’s been highly adherent to antiretroviral therapy for 10 years, attends his appointments regularly, and has had a fully suppressed viral load since shortly after starting antiretrovirals. For him, thinking about the risk that he will transmit HIV onwards, what are the kinds of things that you would discuss?

Chris:
First, you bring up the issue of disclosure, which can be a starting point of discussion, not necessarily whether somebody has to disclose. As you’ve highlighted, things have changed with the advent of very effective antiretroviral therapy, and people being suppressed for long periods of time, compared to years ago when many people did not have virologic control and the risk of transmission was high. There the discussion of disclosure was as a health risk to others, and hurting others by transmitting HIV, it was a big issue.

Now, I’m more often trying to reassure people that they are at very low or at no risk of transmitting HIV, whether it’s through sexual activity, or because they have a cut on their arm, or because they shared a spoon with one of their family members, or other reasons that people may be concerned about HIV transmission, because some sort of body fluid may have been exchanged, such as saliva or blood or sexual fluids. That discussion often comes before getting into the details of a specific relationship, just trying to get a patient comfortable with the reality that even though they are living with HIV, they’re not a risk or a menace to others or spreading HIV.

And that, certainly in this scenario, is important for romantic and sexual relationships, but also, as I mentioned, includes patients who are looking after their grandkids and want to make sure that they’re not going to infect their grandkids. As a healthcare provider living the data day in and day out, I sometimes can lose the perspective of somebody who has grown up through the years and at one time was living in [an] era where transmission was a much bigger issue and the issues around disclosure [were] a much greater concern than [they] may be now.

Eileen:
That’s really helpful, Chris. Thinking specifically about the sexual activity risk is the concept of “undetectable equals untransmittable.” Could you introduce us to what that idea is and how you use that to communicate with patients?

Chris:
It’s such an important concept. It’s been around now for what seems like a lot of years, and we’ll get into the data a little bit more in a moment. But despite that, it’s really not known by a lot of people in the general community or not internalized, so to me becomes a very important message to get patients to understand, that with sexual activity, if their viral load is undetectable, which in U equals U studies has been less than a viral load of 200, they do not transmit HIV through sexual activity. Making that clear and reinforcing that is one of my jobs as an HIV clinician. I also wanted to comment about the overall question about disclosure in the era of U equals U. Disclosure is very complex, whether it’s to family members, other social support network members, or to romantic or sexual partners. I don’t think there’s any one right answer to whether disclosure should happen, because each of these situations is different.

Disclosure of HIV status for somebody who has sexual practices that may be disapproved of by family can lead to disclosure of being gay or bisexual or transgender that may lead to ostracization and abandonment by family members, which can be even more devastating than any benefit that disclosure could have. On the other hand, disclosure can lead to important social support in the right setting. So, I really go through that with my patients and try to discuss pros and cons, that they have to list because they know their life whether it’s with family or with potential new relationships or established ongoing relationships, and try to have them reflect on that. Unpacking this specific situation gets into almost relationship counseling.

Disclosure is not essential, even if they move on to sexual activity, for a variety of reasons. One is that barrier protection, like condoms, reduce[s] the risk of sexually transmitted diseases as well as HIV, but also because of U equals U. If we truly believe it, which I do, that being undetectable is untransmittable, then there’s no risk of harm to a sexual partnership through transmission of HIV. That said, a healthy relationship may involve disclosing things like HIV. In addition, nondisclosure can create anxiety during sex and may negatively impact the sexual experience because of concerns of transmission, even if they [the risks] are zero. So those are all things that I open the discussion with before even getting into ways to further reduce risk of sexual transmission of HIV and other sexually transmitted diseases.

Eileen:
And I think I’ll just add one more layer here, which is it’s really important for us as providers to have a clear handle on the data. Because even in your comments, you said, "if we believe it and we do," but we can’t expect all people who provide medical care to have the full knowledge of what the data [are], which is part of the reason why we’re going to discuss it today, because these are important things for not only patients to know, but also providers to understand what the risks of transmission are. Another question around disclosure is the safety of the individual, because there are some circumstances in which disclosure could lead to interpersonal violence. Something that I routinely address with people who are thinking about disclosing to partners is "How safe do you feel?" and I also offer to have joint discussions with people so that questions that come up can be immediately addressed.

Chris:
So important. Perhaps before we even get into some of the data, you can tell us a little bit more about your patient, who his sexual partners are, or if he has sex with women, with men, and a little bit more about his social history.

Eileen:
He is a man who has sex with men. And as I teased at the beginning, he’s previously mostly found sexual partnerships through apps and did some what was traditionally or previously referred to as “serosorting,” where he identified as HIV- positive and then didn’t really think about his partners very much because he had disclosed in the context of the app. His partners were making their choices based on their own risk tolerance. In this new situation, he’s finding himself in what’s really a loving relationship that he wants to have a sexual component and is trying to manage this. You know, this person didn’t choose him on an app as a sexual partner. They met in real life and are developing a relationship. So, the question here is not one of just choosing a partner, but rather not necessarily factoring HIV status into a partner choice, recognizing that he’s thinking about how he can maximally prevent transmission risk for his partner. It feels like a new situation for him. He is open about his status and has discussed it with this new romantic partner, who he hopes to become a sexual partner, and that partner isn’t overly concerned, it’s more the patient that feels worried. That’s the point that we’re jumping off on in our counseling. Does that help?

Chris:
Yeah. A few other things that I like to know are whether chemsex is involved and whether there’s any injection drug use and especially sharing of any injection paraphernalia, given the separate transmission risk around that.

Eileen:
So, that’s not something that has been part of his sexual history and not something with this current partner. Neither uses illicits [drugs] nor has engaged in chemsex.

Chris:
I’m always excited when my patients have meaningful romantic relationships, whether longstanding or if they’ve not had one, [a] new one. I affirm that, and I tell them that it’s wonderful, because it does suggest that they are starting to internalize or have internalized the normalcy of living with HIV and are able to live a full life. I want them to know that it’s important and not guaranteed and celebrate that step in coming to terms with a diagnosis that for some people can be really paralyzing.

Going back to this patient, [I] always like to discuss how to reduce the risk of sexual transmission. Given that they’re open about each other’s health conditions or at least HIV conditions, I always invite a patient to bring their partner or to schedule an appointment where their partner can come in and can discuss HIV risk. Sometimes people are more comfortable hearing U equals U from a healthcare professional than their partner. Any way to reinforce that is a great opportunity.

Eileen:
I do the same, and I’ve had a number of partners come in for appointments, which usually are kind of joyful encounters because the good things they’ve heard from their partner that they were a little bit worried were too good to be true can be confirmed.

Chris:
While U equals U has become a growing slogan over the last 5 to 10 years, the data that support it go back a long way. You could go to the 1990s, but perhaps one of the first landmark papers goes back to Y2K [2000] and Tom Quinn in a Ugandan cohort. He published a cohort study of serodiscordant couples, and in that study, he looked at seroconversion by the viral load of the person living with HIV. At that time in Uganda, antiretroviral therapy was not available so none of the participants in this cohort study were on antiretroviral therapy. In that study, there was no transmission under a viral load of 1,500. As the viral load increased, the incidence of transmission increased approximately linearly.

Subsequently, there were a number of other cohort studies that demonstrated [a] similar association. Then, in 2008, mostly based on those cohort studies, a group of Swiss physicians came out with the so-called “Swiss Statement” that HIV transmission doesn’t occur when a patient is on antiretroviral therapy and has an undetectable viral load. This prompted a lot of discussion and concern from some more conservative individuals and celebration in terms of others who saw this as a motivator for adherence for HIV testing and for accepting antiretroviral therapy among people living with HIV, as well as [an] opportunity to reduce HIV transmission and incidence. Subsequently, there were some landmark studies that helped to confirm that and really built a solid foundation of evidence.

Eileen:
Chris, I think that you’ve summarized those early studies beautifully, and I’ll just highlight that at the beginning of the HIV epidemic there was an incredibly intense focus on barrier protection for prevention of transmission, and the use of condoms, and we were going to basically condom our way out of this epidemic. I think that ignores some of the fundamental truths of human life and the fact that serodifferent couples exist and will want to have children, and you can’t have a child with a condom unless it’s a problematic condom. Just realities of life where there were going to be instances of sex without condoms between people with different HIV status. Dose responsiveness of transmission risk was a really interesting finding. The differences in susceptibility between females and males, and depending on different sexual practices, can also help us to understand better their risk.

Those early studies provided that springboard for what is the foundational trial evidence for U equals U. The bottom line is that no doctor wants to say to someone, "You’re no risk," unless they really feel very confident of that. All of these studies notwithstanding, I think the discomfort with the statements about risk of transmission needed to be addressed with some careful studies that were done in a randomized way. That’s, I think, what you’re referring to. There are really 4 studies that people reference as the foundational data for the broader recommendations that have led to the endorsement of U equals U. Two of those are from 2016. The first, HPTN 052, which is Cohen et al. in the New England Journal of Medicine in 2016, looked at more than 1,700 serodifferent, male-female partnerships from Malawi, Zimbabwe, South Africa, Botswana, Kenya, Thailand, India, Brazil, and the United States. And they identified no transmissions that were linked, so no transmissions from the partner when the partner with HIV was stably suppressed on antiretroviral therapy with a viral load of less than 400 copies.

The second study from 2016 was the PARTNERS study, Rodger et al. in JAMA in 2016. This looked at more than 1,200 couple-years of follow-up in European countries between serodifferent partners, including 60% heterosexual, 38% men who have sex with men, and again, identified no phylogenetically linked transmissions when on suppressive ART. Here, they defined suppression as a viral load of less than 200.

These studies were followed by the Opposites Attract study, in the Lancet in 2018, that had 588 couple-years of follow up in serodiscordant men who have sex with men recruited in Australia, Brazil, and Thailand. Again, the threshold was a suppression level of less than 200, and there were no phylogenetically linked transmissions. Finally, the PARTNER 2 study, which was in the Lancet in 2019, looked at serodiscordant MSM couples in 14 European countries with over 1,500 couple-years of follow-up and no phylogenetically linked transmission events. So, I’ve now said that 4 times: no transmission events when people were suppressed.

To summarize, these observations have the strengths of including people who were both suppressed and nonsuppressed in various contexts and looking at the association between suppression and seroconversion. They were prospectively enrolled to look at this. They were trials where there was a prospective analysis of the risk of acquiring HIV, as opposed to a cohort study where we look back on things, and where they were controlled for a number of different factors, including their self-report of their status of HIV suppression and careful biologic analysis to see if HIV acquisition did occur, did it actually come from their identified partner? There were a few new HIV seroconversions in these studies, and they were all identified as being from outside partnerships, which is just another reality of life and points to the fact that [these studies were] not super different from normal life, but in fact encompass that kind of an experience. So Chris, when you’re talking about U equals U with your patients, what summary of the data do you offer and do you give them any resources about it?

Chris:
Yeah. So first, these are remarkable studies. I think many people were excited that they were done, and certainly innovative approaches and wonderful work, including naming a study Opposites Attract, one of my favorite study names. One of the things that I highlight to patients after reviewing some of these studies is the numbers. As you said, they obtained behavioral data on the number of condomless sexual acts, and across these studies there were close to 150,000 condomless sexual acts. These aren’t small studies with just a few events trying to come to a conclusion that there’s no risk of transmission but [studies] with a lot of condomless sexual acts, including anal sex, and anal receptive sex, which is the highest risk for HIV transmission when the viral load is not suppressed. That’s one of the things that I mention, especially with anyone who is somewhat skeptical about the results of a study.

There are a few other things that I discuss. First is that the cohort studies, the PARTNERS study, Opposites Attract, and PARTNERS 2 study, all used a viral load less than 200 as undetectable, which becomes very important because, as we all know, blips are part of life, at least in 2026, and a viral load of 40 or 70 still fits within that less than 200 or undetectable rubric.

I want to let my patients know that they should not panic if they’ve had sex with a partner, and the next day they get a viral load back that is 45 and not less than 20. The other thing[s] that [are] important to discuss, depending on the specific patient, with a couple of caveats. One is that none of these studies directly addressed sexual transmission risk to a woman who’s pregnant, a period of increased risk of HIV transmission and extreme risk, if there’s acute infection, to the fetus or unborn baby. The other is with shared injection drug use paraphernalia, where the risk of HIV transmission overall is higher and there’s less of a body of compelling data to demonstrate that there is no risk of transmission.

Eileen:
The other carve out for U equals U has been with breastfeeding and the discussion with individuals about the risks associated with that mode of transmission we’ve actually covered in a separate podcast. But I agree, these data [are] confined primarily to sexual transmission.

I, in general, have the same approach that you do, which is to give patients an idea of the scale of these studies, the fact that they enrolled regular people, that those people were having condomless sex, and that there were not transmissions. I do find that a lot of people are still quite surprised. There’s a billboard that says "U equals U" as you drive into Baltimore, so I feel like this has been filtering into the zeitgeist and the community.

It was, I think, about 5 or 6 years ago that one of our patient navigators spoke with our group about what U equals U meant to them as an individual, as a person living with HIV, in terms of stigma. I think it was an underappreciated source of feeling like you were a risk to others that could be carried by some people.

There’s sometimes hesitation from patients even to accept that this is true, and that’s why all of these patient-years of follow-up do provide a good base for reassurance. The one other thing I’ll just quickly mention is that the duration of suppression is another factor. Typically, we say 6 months of viral suppression before we feel that there [are] the best data for prevention of onward transmission, because in some of the studies there were earlier transmission events that were prior to achieving viral suppression. Again, figuring out exactly when that risk goes away is hard to do. In general, I counsel patients that it’s 6 months and then moving forward from there. I also, like you, Chris, focus on the fact that the lowest threshold used in these studies was less than 200, and while they did quantify most people as less than 50, the cutoff was in fact less than 200, so those viral blips shouldn’t be a massive cause for concern for patients. One of the follow-up questions that I have gotten is "Oh wow, that’s great. That makes me feel so much better, but should my partner be on pre-exposure prophylaxis? What if my viral load comes back up?" How do you discuss that with people?

Chris:
It’s a good question and one that I welcome. The way I approach it is I say that from a purely HIV transmission point of view, there is no risk with U equals U, and that PrEP will not further reduce from no risk, but that if the 2 of them are more comfortable and will be more comfortable and have less anxiety when having sex if the partner who does not have HIV is on PrEP, then I say PrEP is a reasonable approach and let them decide, talk among themselves, or give PrEP a try, or decide that they really trust what I’m saying and trust the evidence and don’t feel like their sexual intimacy will be hindered or otherwise affected by any concerns about HIV transmission.

Eileen:
I love that return to the idea of sexual satisfaction as the key part of the recommendation. I think the other way is to think about, in terms of the risk of viral rebound with continued adherence to oral medications, there’s essentially no risk that there will be viral rebound for our patient. When I’m seeing people in PrEP clinic who have a partner who is suppressed, I do offer PrEP because that is controllable by that individual, the individual who’s potentially at risk, and it can remove some need to feel like you’re policing the other person’s medication adherence if there’s any history of intermittent adherence or if that causes a trust issue. PrEP can be something controlled by the individual at risk, and I think that makes it an attractive part of a discussion. With the HIV seropositive partner remaining suppressed, there is actually no risk and PrEP does not reduce zero.

Chris:
I really like that approach of empowering the individual who is seronegative for HIV. The other thing to remind patients, especially those who may have been undetectable for a long period of time, is that should there be a disruption in their medication supply because of insurance reasons or other reasons, they need to keep in mind that their undetectable status is going to change and they need to adjust their perceptions of risk of onward transmission of HIV.

Eileen:
Let’s say you have this conversation and he says to you, "So Doc, you’re saying I really can’t give HIV to anyone?" And what’s your answer? Do you have any lingering hesitations? Do you ever worry about this?

Chris:
I say, “Sexually you cannot give HIV to anyone as long as you remain undetectable.” I think it gets back to normalizing and the point you made about the internalized stigma and the feeling of being a threat to others. I believe that there’s no risk, and I really want to let my patients know that.

Eileen:
I agree. [These] data that we have accumulated [are] as strong as for almost anything that we say in medicine with certainty. [These data are] very strong, and I think we as providers can do a tremendous service to the community of people living with HIV to really understand that and to give it that full-throated support of “Yes.” It does do a lot of good to people who have been carrying stigma that they may not have even known.

Chris:
The former Chief Justice of South Africa, Edwin Cameron, has said something along the lines of "Internalized stigma or shame is the deadliest thing about HIV," which is so true in so many ways, and U equals U is such a powerful tool to chip away at some of that shame and stigma.

Eileen:
Just to summarize what we’ve talked about today, normalizing the discussion of sexual activity, assuming that it would be part of their lives, is really a part of reinforcing to people that you can have a full life with HIV that involves sexual activity. Moving from that, having a clear discussion about prevention of transmission and really liberating patients from the sense that they are a risk to others. With the transformative data from U equals U going back many years, we had clear indications that risk of transmission was related to viral load and is highly consistent with the fact that suppression leads to no transmission. There’s a number of resources that we’ll put in the show notes that can break down these data in lots of different ways for patients and providers. It’s something that I think we can take into our encounters with patients but also into our encounters with other providers. Because the more we can educate that HIV is like other things, that you don’t present a risk to people around you, the less stigmatized this will be in many different settings. Anything as final thoughts, Chris?

Chris:
Echoing what you just said, and in the show notes a link also to the New York State Guidelines document on U equals U, which provides a summary of many of the studies we’ve discussed and some general ways to approach discussing U equals U with patients.

Eileen:
To our listeners, thanks so much for joining another episode of Viremic. Please send any comments or questions to viremicpodcast@jh.edu. We’ll be back in 2 weeks with a case about new antiretroviral agents, so please join us then.

Eileen:
To our listeners, thanks so much for joining another episode of Viremic. Please send any comments or questions to Viremicpodcast@jh.edu. We’ll be back in 2 weeks with a case about new antiretroviral agents, so please join us then.

Announcer:
Viremic is sponsored by the Clinical Guidelines Program, a collaborative effort of the New York State Department of Health AIDS Institute and the Johns Hopkins University Division of Infectious Diseases.

Visit the program’s website at: HIVguidelines.org.

Viremic’s case discussions are for informational purposes only and not offered as medical or clinical practice advice for patients or clinicians. Any mention of specific medications or commercially available products is a description of use only, not an endorsement

The podcast is produced and edited by Jen Ham and Brian Hatcher with assistance from Jesse Ciekot and Laura LeBrun Hatcher.