Part 1: The Link Between HIV and Substance Abuse

Introduction

HOST: It’s the DKB Radio Hour. I’m Spencer Cannon. This episode is brought to you by an educational grant from Gilead Sciences, Inc. and is accredited by the Postgraduate Institute for Medicine.

Recent advances in medical therapy have changed HIV infection from a death sentence to a serious but manageable chronic disease. HIV infection cannot yet be cured, but infected people who receive appropriate medical care can now expect to live many, many years.

But getting there can be challenging, especially for people struggling with addiction in addition to HIV. Appropriate treatment begins with screening and diagnosis, overcoming barriers to treatment and adherence, and collaboration between caregivers. Just as important are efforts to prevent HIV infection in the first place, and we have new tools that can help in this effort as well.

Drs. Glenn Treisman, Eugene Meyer III Professor of Psychiatry and Medicine at the Johns Hopkins University School of Medicine; and Kathleen Brady, Distinguished University Professor at the Medical University of South Carolina, discussed this issue at the 2017 American Society of Addiction Medicine, or ASAM, conference in New Orleans. Let’s begin with Dr. Treisman. In this segment, he introduces a bright young man named Jason who struggled with addiction to opioids.

Jason – Part 1

DR. TREISMAN: Jason grew up in an upper-middle-class home. He was in the middle of his family siblings. He was one of those kids who always kind of got whatever he wanted. He was gifted in many ways. While he was in high school, he had done a lot of partying and drinking, but also pills. He said he would go to parties and there would be a bowl of pills on the table. Everybody would bring pills from their parents’ medicine cabinet and pour them in, and they called it the candy bowl. They would grab a few things and try them out, and he took all kinds of stuff.

In college, he continued to do this and continued to party quite heavily, but he noticed that the drugs that made him feel best were opiates. He learned to recognize opiates in the candy bowl and would pick out particularly oxy and other opiates, oxycodone, OxyContin, Percocet, and he said that those were the things that gave him this sense of inner peace that he thought was particularly delicious. He said it was sort of the best thing.

He was doing okay in school and then had what was the worst thing that could happen to a kid like him. He had an injury and went to a doctor who gave him oxycodone and said, “Take what you need.” And he did. He took what he needed, which was all of it, and he very quickly escalated his dose. The doctor just kept giving him more and more. Jason said that he had terrible chronic pain, and the doctor gave him more and more narcotics. He said it was out of control right away. Before that, he’d have to look for drugs, but now, his doctor encouraging him to take more, so he was taking more. The doctor said, “Pain is a bad thing, you shouldn’t be in pain.” And he wasn’t.

After a while, that doctor was replaced with a new physician, and when Jason went to t get more opiates, the new doctor cut him off. This was a terrible problem. But he knew a lot of kids who used opiates and he went around and got opiates from various friends. After a while, he started to hang around with a group of people who were heavy opiate users and he began using heroin.

When they couldn’t get opiates, they used heroin. Most of these kids were his college friends, and he thought it’s going to be okay, these are my college friends and there was no big deal. He shared needles, but he shared needles with other college kids and didn’t think it was any big deal.

Then Jason realized that his grades were falling off; he was slumping, and things were really falling apart. That was a really bad thing for him and thought he better get help. He always thought he was the kind of person who would never get addicted, but realized he was addicted and went to a treatment center and was admitted, detoxified, got treatment. Came back to school, relapsed, went back, got treated again, and finally it stuck and he got sober.

He was somewhat mortified by how badly he had done but also realized that addiction was a serious problem and so was chronic pain. He realized that he really wanted to help people with this same problem and decided to go to medical school. So, he did a postbaccalaureate program, worked really hard, got great grades, and applied to medical school.

HOST: Jason may feel familiar to many of you — a young person who gravitated toward prescription drug abuse, first as an occasional diversion, then, following an opioid prescription for chronic pain, as a full-blown addiction. Like so many others, his drug-seeking behavior eventually led him from pills to heroin.

We know that sharing needles, as Jason did, is a risk factor for HIV transmission. But how great is this risk? And how else does addiction affect HIV?

To tell us more about the interaction between HIV and addiction, and particularly opioid addiction, we turn to Dr. Kathleen Brady and her talk from the ASAM stage.

Role of Substance Abuse

DR. BRADY: One of the things we know for certain about substance use is that current alcohol and drug abuse is associated with poor treatment outcomes and incomplete courses of either HIV or HCV treatment. ^{1 2} Addiction is also associated with viral resistance and increased mortality. ³ Collaborative treatment — by that I mean collaboration between the people who are getting the drug abuse treatment, the drug abuse treatment setting, and primary care or specialty practices where these infectious diseases are treated. When there’s collaboration between these treatment settings, both for testing, prevention efforts, as well as treatment, it really improves outcomes. ⁴ For opiate addiction, substitution therapy is by far the best-studied intervention, and it has been shown to have improved outcomes for both HIV and HCV infection. ^{5 6 7 8}

HOST: So clearly collaboration between providers is key, but just how much does injection drug use contribute to new HIV infection? Dr Brady explains.

Injection drug use is responsible for about 6% to 8% of HIV transmission. The highest percentage of HIV transmission is from men having sex with other men. Twenty-four percent of the transmission is through heterosexual sex. Eighty-one percent of new HIV cases were in the 20 to 24 age range, so this is a very young population becoming newly infected.⁹

HOST: Dr. Brady tells us that HIV is no longer the disease we may have thought it was 30 years ago. Tragically, and despite decades of education, young people are now the face of the epidemic. And although injection drug use does not account for most HIV transmission, it broadens the pool of infected people and puts yet more people at risk for transmission through sex, drug use, or other means.

How we got here is something that addiction specialists know too well — a common pathway is the widespread use of opioids for the treatment of chronic pain, despite the availability of other effective therapies.

We called Dr. Marc Fishman, Medical Director of Maryland Treatment Centers, and asked what clinicians can do to address HIV in the setting of addiction.

DR. FISHMAN: It is so important these days for us to be doing universal screening so we can get early detection and case detection, diagnosis, and early treatment for HIV, especially in the addiction treatment setting, with its high-risk population.

The CDC has called for universal screening of all persons at least once and for high-risk individuals at least once a year. ¹⁰ Our patients are all high risk. Remember that we’re not just talking about injection use as the primary means of transmission, although that’s certainly important. We also don’t always know whether patients have used needles because there’s stigma and they may not want to be honest about it, or it may be past needle use, not current needle use.

Remember, men having sex with men is the biggest transmission route in the United States, ¹¹ but heterosexual transmission is also a very big transmission route. And among our patients, the intermingling of patients with high-risk sexual behavior is a very high-risk factor, so we should be screening everybody.

That doesn’t happen as much as it ought to for a variety of reasons, which we’ve discussed, but we need to do a better job.

All in all, we have every reason to do universal screening and we should do everything we can to train and encourage the addiction treatment provider community to do a better job with this, it is so vital.

HOST: So, for those of you working in addition clinics — remember, the CDC recommends screening people at risk at least annually. Other adults and adolescents should be screened at least once. Let’s return to Dr. Treisman at ASAM, where he described his patient Jason’s experience with HIV screening.

Jason – Part 2

DR. TREISMAN: So, Jason knew he was in a lot of trouble, decided he needed to get treated, and went to an addiction inpatient program for detoxification treatment. He did very well the first time. But he relapsed and then went back for a second visit and was detoxified a second time, and that one seemed to stick.

One of the things that came out of that was that at no time during either admission for detoxification did they talk about screening or testing for HIV or hepatitis C, and so he didn’t get testing. At the time, he said it wasn’t surprising to him because he was a college student and all the people he used drugs with were college students and his friends, and he didn’t think he was at any risk, and apparently neither did the people at the addiction program.

HOST: It is unfortunate but true that addiction medicine specialists, like other clinicians, do not always follow current guidelines for HIV screening, even for high-risk patients. But why aren’t patients like Jason being screened? From the ASAM stage, Dr. Brady addresses this question.

Barriers

DR. BRADY: Why would that be? We’ve got pretty clear recommendations, but in fact, there are a number of barriers to HIV screening, and these barriers are multifactorial and complicated, so you need a multipronged strategy to overcome those barriers. The barriers occur at several levels: at the patient level and the provider level, and at the system level. There are barriers such as access, cost, and some policies and legislation that in some ways can work against screening.

Let’s start with the patient-level barriers. Stigma is a big one. ¹² These are stigmatized illnesses. Although we’ve come a long way in raising public awareness, HIV remains a disorder that people are ashamed to talk about having. Because of that, they fear discussing it with the provider ¹² and asking for testing.

This fear may be based on a couple of things. They may be worried that if they are HIV positive there will be some discrimination against them because of their status. They may be worried that even asking for the test implies something about them or their lifestyle that they don’t want their physician to know. Also, many people are unaware of the new HIV treatments and view the diagnosis as a death sentence. ¹²

This lack of patient knowledge on a number of levels makes them reluctant to discuss HIV with their providers. Often, they are unaware of the risk factors for HIV, they’re unaware of the confidentiality of their results of testing, unaware of improved and accessible treatment, and unaware that the diagnosis of HIV is no longer a death sentence at all.

HOST: Patient-related barriers are only part of the problem. Health care providers sometimes have their own set of barriers that get in the way of screening and care. We’ll hear from Dr. Brady that those barriers can vary depending on the setting.

DR. BRADY: The barriers in substance-use treatment settings may be very different. In many substance-abuse treatment settings there are no medical providers or very few only coming maybe once a week. And so often the providers in substance-use treatment centers, the counselors, feel not capable of addressing the issues, answering the questions, and don’t have the tools that they need to provide the testing.

HOST: Those barriers described by Dr. Brady are not indestructible. We must and need to be sure our patients are screened and, if necessary, referred for treatment for HIV.

Here’s Dr. Fishman, who discusses the importance of overcoming barriers and how to do so.

DR. FISHMAN: It is true, there are a number of barriers, both at the patient level and at the provider level. So, it’s important that we help people understand why this is so good for them. They may not understand that they’re at risk for reasons other than the obvious. Lots of people don’t even know about heterosexual transmission. And so, educating patients is very important.

There are provider-level barriers, as well. Boy, I don’t have to tell you guys that as an addiction provider we’re busy, we don’t have enough time, we are under-resourced, there’s never enough to be able to give what we need to give to all the patients. So, lack of resources and lack of time are certainly issues.

It may seem to addiction counselors and providers that they’re not medical folks…they’re not infectious disease specialists, this isn’t central to their mission, but I think it is important that we shift the paradigm to see that this ought to be a routine part of substance-use disorder treatment. Even if you’re not a physician, even if you’re not a subspecialist physician in infectious diseases, you have a part to play.

So, this education and training, getting addiction counselors and other providers comfortable to be able to have these conversations with patients just to be able to simply get them to be willing to do the assessment and the screening, to do the case detection, and then, if positive, to encourage them to go on and seek further care.

HOST: Think about your own practice for a moment — which of these barriers do you recognize, and how have you responded to them in the past? Remember that early detection and treatment can improve outcomes and limit risk for transmission.

This brings us to an important point, which is how to stop the spread of HIV. Here to explain is Dr. Treisman from ASAM in New Orleans.

PrEP

DR. TREISMAN: So how can we stop HIV transmission? Clean needles, safer sex, opiate-substitution therapy; that is, putting people who are using injectable opiates on Suboxone and methadone. Substance-abuse treatment in general, 12-step programs, inpatient detoxification, rehabilitation. Psychiatric treatment, including treatment of the comorbid conditions that drive substance abuse and high-risk behavior, and then treatment as prevention and PrEP. And PrEP has been shown to be effective in decreasing transmission of HIV in several studies that are quite important.

HOST: You heard Dr. Treisman mention something called PrEP. PrEP is pre-exposure prophylaxis, and this is the new tool we mentioned at the beginning of the show that can help prevent HIV infection for certain high-risk patients. PrEP is a specific, fixed-dose combination of medications, tenofovir and emtricitabine, that can be taken by people who do not have HIV but engage in behaviors that put them at high risk for acquiring HIV.

Let’s listen as Dr. Treisman discusses the efficacy of PrEP in clinical trials from the stage at ASAM.

DR. TREISMAN: Most of the studies of PrEP have been used in HIV serodiscordant couples — when one partner has HIV and one partner does not. The most successful trial of PrEP reduced the risk by 92%. ¹³ It probably would have been 100% if all the people took it correctly. ¹⁴ So it works if the patient takes it, and you should know your patients.

This is not a drug that works from a vending machine. In the unsuccessful trials with PrEP, mostly the drug was given out without much connection between the doctor and the patient, and in those circumstances, people tend not to take the medicine and it tends not to work.

How about people with substance-use disorders — people who are using currently? Does PrEP work? There is only one good trial, but quite remarkably, it’s a good trial. ¹⁵ It’s a randomized, placebo-controlled trial of adequate size in a population of people who are substance users— an amazing accomplishment. There were 2,413 participants and 1,204 got tenofovir and 1,209 got placebo. In the tenofovir group, 17 became infected and in the placebo group, 33. So that’s a reduction of half, and it was statistically significant.

This is quite a remarkable study because people don’t usually like to study HIV substance-using patients, and this trial showed that even in a group of people who are actively using at the beginning of the study, PrEP is effective.

HOST: So, studies show that PrEP can prevent HIV infection in high-risk populations, including people who inject drugs.

Here’s Dr. Michael Saag, Professor of Medicine in the Division of Infectious Diseases at the University of Alabama at Birmingham, who describes how preventive measures like PrEP work.

DR. SAAG: The trick here is to identify people who are at high risk, bring them into care, document that they do not have HIV infection by a blood test, check them for some general safety labs like creatinine and liver function, and their blood counts, and then counsel them on how to appropriately use PrEP and also advise them to continue to use condoms, not only to help prevent HIV, but to reduce the transmission of other sexually transmitted diseases, such as syphilis.

HOST: To illustrate the effect of intervention such as PrEP on an ongoing outbreak or epidemic, Dr. Saag talks about a recent example. Hear how an astute physician who alerted the CDC helped to avert what could have been an even bigger health crisis.

DR. SAAG: In late December, 2014, a Scott County, Indiana physician in a small community named Austin started noticing two to three cases of HIV that was diagnosed but had not been seen before. ¹⁶ Previously, Scott County only had five total HIV-infected people and now they’re seeing three. Over December and January, another four or five individuals were identified, and these folks were referred to the state health department. By February, eight more infections were identified, and by March the CDC was called in.

The HIV transmission was almost exclusively through intravenous drug use, primarily involving oxymorphone, which is an opioid, that would be ground up and then injected. The injection practices were multigenerational, often occurring in the same family, with two to 20 injections per day, and up to 20 needle-sharing partners might use the same needle.

By the time March 2015 arrived — now three months into this — up to 55 new cases of HIV were diagnosed, and this number ultimately expanded to 188 total cases of 513 contacts who were identified as possibly being exposed. That’s a 38% positivity rate among the tested contacts.

The CDC, after being called in, reached out to the Indiana University Ryan White Clinic with Diane Janowicz, and Diane came down and opened a clinic that began to solve the problem. The clinic was called Austin’s One-Stop Shop, which did HIV and HCV testing, collected vital records, driver’s licenses and state IDs were issued there, insurance enrollment, immunizations — kind of a comprehensive health and services community outreach center. Very importantly, they also provided care coordination and needle-exchange programs. And when they started doing that, the incidence of new HIV infections dropped, and by April 2016, no further cases had been transmitted. So, this was an effective intervention that worked extremely well.

This is an example of how the emerging or exploding opioid epidemic was borne out in one small county in southeastern Indiana, and how rapid intervention and recognition of these new cases led to control of what otherwise might have been a much worse epidemic.

HOST: Dr. Saag showed us how preventive measures like syringe-exchange programs and PrEP might have been able to prevent a local epidemic, such as what occurred in Scott County. And studies indicate that PrEP can reduce transmission, even among people who inject drugs.

Based on these studies, the CDC recommends PrEP for people who are HIV-negative but have high risk for HIV infection. ¹⁷ This includes gay or bisexual men who have had anal sex without a condom or who have had a sexually transmitted infection diagnosed in the last six months; men who have sex with both men and women; heterosexual men and women who do not regularly use condoms during sex with high-risk partners of unknown HIV status; and people who have injected drugs in the past six months and have shared needles or have been in drug treatment in the past six months.

Now, here’s Dr. Treisman again from ASAM to help us understand how these data and recommendations apply in clinical practice.

DR. TREISMAN: If it works, why are we not giving it to our patients? Well, it failed in some studies because of poor adherence, but we also don’t want to pay for lots of things that we know work: addiction treatment, opiate substitution, clean needles, rehabilitation, integrated care, and treatment of psychiatric comorbidity. We know these things work and it’s very difficult to get them paid for, and PrEP will be similar in that our patients are going to be discriminated against because people won’t want to spend the money to give them PrEP.

Current arguments against PrEP include poor adherence, which can lead to infection and even resistant viral infection, ¹⁸ expense; medical risk; and burden of monitoring. Fears about people sharing medications and selling it, although this turns out not to be true. People did not sell their PrEP drugs in any of the studies and learning how to do it and getting the word out to patients.

We need resources, psychiatric care, and integrated treatment to reduce failure with PrEP. Therefore, if you have people who are already in treatment, PrEP is a better idea rather than a worse idea. How do you offer PrEP? You need to give patients a thorough education about the need for adherence, you need to discuss safe sex because syphilis epidemic and other STDs are running wild, particularly on the West Coast, but also through the whole country. And people who use PrEP might think they don’t need to practice barrier resistance, but they do.

You need to test for hepatitis, even though you’ll be treating in part hepatitis B, you need to test people for hepatitis before you give them PrEP to make sure that you are not going to make it harder to treat their hepatitis. You also need to monitor adherence and renal function.

There is only one approved drug for PrEP. It causes nausea and relatively few other side effects, and it’s easy to use. There is only one dose, there is only one drug, so education for the physicians and other practitioners is pretty easy.

Poor adherence to PrEP can cause antiviral resistance, ¹⁷ and FTC and 3TC have overlapping resistance, so if you lose FTC you also lose 3TC; however, there’s lots of other choices. Tenofovir and TAF have overlapping resistance, but this is rare even in people who develop resistance. So, in people who develop resistance, it’s almost always the FTC side of the coin, and tenofovir tends to continue to work.

TAF is not approved for use in PrEP. You’ll hear more about TAF in the next part of this program, but TAF is a form of tenofovir that has fewer side effects but is not approved yet for PrEP and probably shouldn’t be used as the studies are not done.

HOST: Dr Treisman mentioned several drugs, FTC, 3TC, and TAF, that are used in preventing and treating HIV. You will hear more about these later.

Part 2: Approaches to Treatment

Introduction

HOST: It’s the DKB Radio Hour. I’m Spencer Cannon. This episode is brought to you by an educational grant from Gilead Sciences, Inc., and is accredited by the Postgraduate Institute for Medicine.

Welcome to Part Two of our series on the diagnosis, prevention, and treatment of HIV. In Part One, we talked with experts about the link between HIV and substance abuse. Drs. Treisman and Brady, speaking from the 2017 American Society of Addiction Medicine, or ASAM, conference in New Orleans, highlighted the importance of screening and early diagnosis in high-risk patients. We also discussed PrEP, a new tool to help prevent HIV infection in some people with high-risk behaviors.

In Part 2, we will discuss approaches to the treatment of HIV infection. Novel agents and regimens continue to be developed. These new therapies have changed HIV infection from a death sentence to a manageable chronic disease for most patients. But successful treatment depends on close collaboration between addiction specialists and other health care providers to promote patient adherence and minimize risk for adverse events.

Although HIV infection cannot yet be cured, most people who are infected with the virus and receive appropriate medical care can now expect to live many, many years. Getting there can be challenging for some patients, especially those with a history of substance abuse.

To illustrate some of these challenges, we turn to Dr. Treisman. In Part 1 of this series, Dr. Treisman introduced Jason, a young man with a history of opioid addiction. From ASAM, Dr. Treisman continues Jason’s story.

Jason Part 3

DR. TREISMAN: Jason was, when we last saw him, off to medical school. He finished medical school, did very well, and while in medical school he met the girl — “the one.” He was several years older than the other students and in his second year of medical school he met Alice, who he thought was the perfect girl. As he was getting serious about her, he went to the doctor and said he want to be tested for everything. He said he injected some drugs and wants to make sure that there isn’t anything to worry about. He admitted that he had many sex partners as an undergraduate, but that he always used safe sex. Still, he wanted to be sure.

He was shocked to find out that he was HIV infected. He was mortified by this and it really shook up his world. He went to see his doctor, he talked about various options. He got on HIV therapy, which contained a drug called efavirenz, and on efavirenz he got quite depressed. He also was terrified that he had given his girlfriend HIV.

Now, he had been using condoms with her because, as he described it, he always used condoms because he didn’t want anybody to say that he had gotten them pregnant and have trouble. So he was in the habit of using condoms. But here he was, HIV infected.

He immediately told his girlfriend with the help of his doctor. She got tested and was negative, which was a relief. He was also negative for hepatitis C. But he was very frightened about passing his HIV on to his girlfriend, very frightened about how he was going to live with HIV, and it didn’t help that he got quite depressed and became much more negative about things. Luckily his doctor recognized his depression and helped him change medications so his depression got better.

But he was worried about infecting Alice. He didn’t want to infect her, so they were going to continue to use condoms. He decided that he would get PrEP for her, and after talking about PrEP with the doctors she decided that a reasonable thing would be for her to go on PrEP, even though Jason’s viral load was undetectable.

One of the interesting things was that he expected her to leave him. She was very responsive to his being honest with her, being concerned about her, and quite remarkably, it probably improved their relationship rather than hurting it. She knew quite a bit about HIV by the end of the conversation, knew that he would probably have a normal lifespan, and knew that he could take care of himself and be healthy and also that they could have kids, they could have a normal life together. And so, she was very enthusiastic about the fact that he had been honest with her immediately, that he tried to protect her from getting HIV, and that he’d use condoms but also that he was taking his medicines and had an undetectable viral load.

So, their relationship continued and they continued to thrive.

HOST: Like many people who share needles, Jason became infected with HIV. But he only discovered his condition years later, after he had successfully quit using opioids. Fortunately, Jason had always used safe sexual practices; if he had not, he could have contributed to the spread of HIV. His story highlights the importance of screening patients with risk factors for HIV, including people who use injection drugs.

Once his HIV was diagnosed, Jason started a guideline-directed therapy, which had some side effects that required a change in therapy. Side effects are one of the key issues in the management of HIV. To tell us more about current issues in HIV care, we return to Dr. Treisman from the ASAM stage.

Adherence

DR. TREISMAN: I want to spend a few minutes talking about the problems that we face in the HIV epidemic, both as substance-use doctors and as physicians in general. Currently, the best result we can achieve with HIV is an undetectable viral load, unlike hepatitis C, where we can actually cure the virus. With hepatitis C, after 12 weeks of therapy, you’re cured and you don’t have a viral infection at all.

With HIV, although we can make viral loads undetectable, even after several years of treatment if you stop the meds, the virus comes right back, so right now this is a lifelong treatment. We have to give three drugs from two to three classes of drugs. Although there is conversation about whether people can get by on two drugs now because the drugs are so potent, we’re still using three drugs.

Noncompliance with HIV medications leads to antiviral resistance, ¹⁷ and there are people around who are resistant to a lot of the drugs that we have now. Some of them are very difficult to treat, either they were infected very early or they had lots of noncompliance.

Lots of new formulations require one pill once a day, which is very exciting. One-pill, once-a-day therapy means people don’t have the burden they had even a few years ago.

HOST: Even with viral resistance, sometimes caused by poor adherence to HIV medications, treatment is still possible. And new formulations make it easier for people to adhere to treatment. But getting them into care in the first place can still be a challenge.

Spectrum of Engagement in HIV Care

DR. TREISMAN: This next conversation is about the spectrum of engagement in HIV care. This study looked at the patients who are infected across the US, and then looked at how many people who receive diagnoses are linked into care, retained in care, need antiviral therapy, are on antiviral therapy and are adherent or undetectable. ¹⁹ And as you can see, when this study was done quite a few years ago in 2011, a lot of patients were infected and only a modest number were adherent and undetectable. We are certainly doing better than we were in 2011, but a huge number of patients still need to be identified, linked into care, and treated.

We’re not adequately keeping people in care. This process requires more and more connection to the patients, and part of the issue is that our patients have inadequate resources. In underserved areas, in underserved populations, engaging people in care is difficult.

HOST: The goal of HIV treatment is to attain an undetectable viral load — this is not the same as cure, as in the management of hepatitis C, but it can keep patients healthy and prevent transmission of HIV to others. The good news is that new regimens that combine multiple recommended drugs into a single pill that can be taken once a day are available. But as Dr. Treisman noted, patients have to be engaged in care for treatment to work, and engagement can be a hurdle in the addiction medicine setting.

To better understand these issues, we called Dr. Kathleen Brady and asked how to foster engagement and adherence in patients with HIV.

DR. BRADY: Medication adherence is a multifaceted construct. Some of the factors that influence medication adherence are things within the patient, characteristics of the patient, but external and environmental factors can also influence medication adherence.

What are those environmental factors? Certainly, the more you can simplify the regimen, the fewer pills per day, or tying their medication to a meal or some other event, it becomes very automatic.

It’s also important to talk to patients about why they are taking these medications and how the medications should help and listen to any concerns they might have about taking the medications. Also address side effects aggressively; ask about them and do whatever you can to address those side effects.

Other issues such as addictions and depression and cognitive impairment can interfere with medication adherence in HIV treatment, ²⁰ but those things can be addressed to some extent.

Finally, addiction, in and of itself, can interfere with compliance or adherence to medications for a number of reasons. Addictions interfere with people’s cognitive processes and memory, particularly when people are actively using. And when people are in the throes of addictions, they sometimes reorder their priorities so that nothing is more important to them than their drug of abuse.

So, it’s important if adherence becomes an issue in somebody with a history of addiction, to have an ongoing assessment of their substance use with your indirect screens, and just asking them. You want to have collaborative arrangements, addictions are chronic in relapsing illnesses, so people need to be in treatment. Maybe it’s not very intensive treatment if they’ve been in recovery for a while, but they still should be in touch with a recovery-related group or a counselor.

Helping patients find and initiate substance use treatment can be one of the most important things you can do in treating someone who has an addiction and is on HIV medications.8

HOST: As Dr. Brady emphasized, no clinician can do this alone. Maintaining adherence to HIV therapies for patients who are addicted requires close and ongoing collaboration between addiction specialists, HIV clinicians, other health and support services, and of course your clients, with shared decision-making.

Collaborative Care and Available Treatments for HIV

HOST: Here’s Dr. Treisman again to discuss the importance of collaborative care for patients with HIV and addiction.

DR. TREISMAN: I want to mention collaborative treatment. We need to include mental health, hep C and HIV, and general health care in substance abuse programs and vice versa so we can have better outcomes. Collaborative care is critical to better outcomes, and everybody who’s studied this has shown that including opiate-substitution therapy in HIV care leads to better outcomes. ²¹ And no matter how you do it, when you integrate care rather than disintegrate care, you have better outcomes.

HOST: We now have some perspective on the approach to managing HIV in people with addictions, and this approach emphasizes collaboration between multiple disciplines to treat addiction, comorbid mental illnesses, and HIV itself. What we haven’t yet discussed are the currently available treatments for HIV, how they work, and what’s recommended.

We called Dr. Richard Moore, Professor of Medicine at Johns Hopkins University School of Medicine, to help us understand how available therapies affect HIV.

DR. MOORE: Thank you. The way that available therapies work is by inhibiting certain steps in the HIV life cycle. ²² There are multiple steps in this life cycle. Our most commonly used drugs, the backbone of most of our therapies and the initial drugs developed, are called reverse transcriptase inhibitors. They inhibit the particular step in the life cycle with the reverse transcriptase that creates the DNA from the viral RNA.

We also have other types of drugs that inhibit other parts of the life cycle, including protease inhibitors, integrase inhibitors, and various entry inhibitors. And there’s a mixture of those. There are fusion inhibitors, coreceptor inhibitors and others such as CD4 and GP120 inhibitors. Most of these drugs are used currently to treat HIV.

One of the things that we learned very early was that a single drug does not work well. It will suppress virus for a short time, but because of the very rapid mutation that occurs daily in this virus, there’s a quasi-species of virus that will occur sometimes within hours, sometimes within days, that will render a single drug ineffective. So, we have learned that we require multiple drugs to be given together to suppress the virus. Currently, that is three drugs, ²³ almost always including reverse transcriptase inhibitors with an additional drug which might be a protease inhibitor or an integrase inhibitor, for example. We have learned is that it is very unlikely for a virus to develop single virus quasi species mutation to all three drugs simultaneously, which is why the combination or multiple drug therapy works.

HOST: Dr. Moore described how therapy using a backbone of nucleoside reverse transcriptase inhibitors plus another highly effective drug, such as an integrase or protease inhibitor, can successfully inhibit HIV replication.

Now Dr. Treisman will tell us which of these agents and combinations are recommended for the treatment of HIV in current guidelines.

DR. TREISMAN: Current treatment recommendation are two nucleosides, two “nucs,” reverse transcriptase inhibitors as a backbone, and then a third highly effective drug. ²³ These are the NIH guidelines, tenofovir and FTC in a fixed-dose combination, tenofovir/alafenamide, TAF, and FTC, and then abacavir/lamivudine, which is only used for certain patients but is a very effective combination, as well. The third highly effective drug is usually an integrase inhibitor, but it can still be a protease inhibitor.

These are the recommended first-line regimens, but we have lots of other regimens. The other drugs are still very vital and widely used. But if somebody rolls in now, it’s as simple as this, with these NIH guidelines, to start people off.

HOST: Dr. Treisman mentioned TAF— a relatively new agent now included in guidelines. TAF is tenofovir alafenamide, which is a new way of delivering the widely used HIV drug tenofovir disoproxil fumarate, also known as TDF.

We return to Dr. Moore, who tells us more about this new agent and why guidelines are moving away from TDF and toward TAF.

DR. MOORE: Tenofovir alafenamide fumarate, or TAF, is a prodrug of a tenofovir preparation that we were previously using called TDF. This prodrug provides similar antiviral efficacy with much smaller doses than the previous TDF and has fewer adverse effects on the kidneys and bones. ²⁴ We are able to give it with less toxicity. TAF is tolerated better and at lower doses, ²⁴ which has caused it to be a very attractive drug to be used in combination therapy for HIV.

Currently, TAF is only approved for treating HIV. It is not currently available for PrEP, for example, as there are still questions about whether there are adequate tissue levels for that purpose. There is a clinical trial going on studying this, but the answers are not yet in.

HOST: So TAF is another step in the evolution toward more tolerable and more effective regimens.

Another major step along this path was the development of one-pill, once-a-day regimens that contain recommended combinations of agents. There are now several once-daily regimens available in the US, and they are an important component of our efforts to minimize the burden of treatment and maximize adherence.

Remember that a high level of adherence to antiretroviral therapy is essential to minimize viral load and prevent the development of viral resistance. What else helps? Treatments with fewer side effects and less complex monitoring, and the prevention or management of comorbidities. In short, the simpler the regimen and the healthier and happier the patient and your client, the better the chances they’ll be successful in achieving and maintaining their treatment goals.

Before we close, let’s return to Dr. Treisman and his patient Jason to see what challenges he encountered and how he overcame them.

Jason Part 4

DR. TREISMAN: So, Jason had switched to a less depressive regimen; his reaction to efavirenz with a depressive result had gone away. He was going very well and was sailing along, but he suddenly found out that he had to have a surgery. The surgery was a cyst removal, it wasn’t huge, but it could get into his peritoneum. He was quite worried about pain, but also quite worried about using opiates.

He and his girlfriend went to the doctor. He told her that if he were given oxy it would be dangerous, and his doctor talked to him about opiates and careful monitoring. He agreed to have urine toxicology screens and he agreed that when he had his surgery, if he absolutely needed opiates he would have it only in the hospital and would stay in the hospital until he could get off opiates.

His physician was understanding about this and talked with the surgeon. The surgeon was understanding about it as well. They talked about Ketorolac, an injectable nonsteroidal antiinflammatory, which for some people is perfectly adequate for surgery, even fairly substantial surgery, but also talked about the fact that if he got reexposed to opiates he would have a fairly substantial risk of relapse, and that probably for some time after the surgery it would be a good idea for him to be monitored and for him to give urine samples for testing.

So, they continued in medical school, and his surgery was uneventful. They went on to do their residencies together, the couple matched and were married eventually and are doing okay. I’m still in touch with Jason, although I don’t see him regularly because he lives in another city. He has come back once to visit and he and his wife are doing great.

HOST: Jason’s story demonstrates how opioid addiction and HIV infection can change a patient’s life. In the end, effective management of his addiction and HIV infection helped Jason achieve his goals, both for his health and having a normal life. His story shows us what is possible for patients with addiction and HIV.

In closing, we turn once more to Dr. Treisman, who leaves us some key messages from our program — and one tantalizing possibility.

Key Takeaways

DR. TREISMAN: There is one known HIV cure, the famous Berlin patient, 40-year-old patient with HIV who developed acute myelogenous leukemia. He got a bone marrow transplant with a CCR5-delta-32 mutant, relapsed, and had to have a second one. ²⁵ After two bone marrow transplants he seems to be cured of HIV and has been cured for many years now. This is a very exciting development because it proves that HIV can be cured. Bone marrow transplant is not reasonable as a treatment because of its risks but trying to find ways to do the equivalent for patients is very exciting. Numerous cure investigations are currently going on, and we’re waiting to see the results of some of them. Some of the studies are very exciting.

Takeaways for today are: there are numerous highly effective, low-side-effect, one-pill, once-a-day regimens for HIV. HIV has become a chronic disease and transmission is preventable. We should be testing our patients for HIV and hepatitis C in the substance-use world, and we should be getting them into treatment.

Finally, what’s most important is this: collaborative treatment of HIV has the best outcome. You have to treat the medical comorbidities of HIV, you have to treat the psychiatric comorbidities of HIV, and you have to treat the substance-use comorbidities of HIV. You also have to treat HIV as a comorbidity of substance use and psychiatric disorders. Which means if you can get all three providers in the same clinic at the same time, you do much better.

If you’re in an environment where you can’t do that, one of the questions people always ask is, “What can I do?” Well, you can develop a virtual version of that. You can make collaborative relationships with people in other treatment programs around your area. HIV providers can collaborate with substance-use providers and with mental health providers, and you can improve the outcome for patients by being able to shuttle them back and forth between people who are working together trying to get the patient better. That seems to have the best outcomes.

So, although I want you all to fight and press for more integrated treatment and less disintegrated treatment, get rid of carve-outs, put mental health and substance-abuse treatment back into the general clinic, I also want you to be able to work with what we have realistically right now, which is to create virtual versions of collaborative care.

HOST: We hope you’ve enjoyed this episode of the DKB Radio Hour. Please join us for future episodes of the Radio Hour, when we discuss HIV and other topics.

I’m host Spencer Cannon, thanking you for your time.

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