ANQUOINETTE CROSBY: Welcome to our webcast. I'm Anquoinette Crosby. Nucleoside reverse transcriptase inhibitors, or NRTIs, were the first class of drugs used for the treatment of HIV. They can be highly effective when combined with other therapies, but they also come with potential side effects.
Here with me to talk about these side effects and what can be done to reduce them is Dr. Richard Elion, a physician in private practice in Washington, D.C. Thank you, doctor, for joining us. Also joining us from New York is Dr. Brian Boyle, Assistant Professor of Medicine at Weill Cornell Medical College.
Dr. Elion, what are the NRTIs, and how do they work?
RICHARD ELION, MD: NRTI is an acronym for nucleoside reverse transcriptase inhibitors, and those are the first class of drugs used for HIV. What they do is they prevent the RNA to be transcribed into DNA.
ANQUOINETTE CROSBY: What are some of the general side effects of the NRTIs?
RICHARD ELION, MD: Some of the general side effects of the NRTIs are, in combination with proteases, they seem to cause some changes in body composition, lipoatrophy and lipodeposition. In other words, the loss of fat and the deposition of fat. There are also some specific side effects -- anemia, some weakness of muscles, some neuropathy, some pancreatitis that's been associated with some of them, and those make up the majority of the side effects.
ANQUOINETTE CROSBY: Dr. Boyle, can you tell us how the side effects have interfered with your patients' adherence to treatments?
BRIAN BOYLE, MD: The side effects patients commonly encounter vary a lot, depending on which particular medications they're on. For example, AZT, also known as Retrovir, may have a lot of fatigue, may have some muscle aches, headaches and other symptoms. So I think that to say overall which side effects patients are going to have with antiretrovirals is relatively difficult, because it's going to vary a lot depending upon the individual medication, depending on how the medications are put together, and depending on the individual patient. Different patients have different side effects, depending upon the medications that they're on.
ANQUOINETTE CROSBY: Dr. Elion, why are the side effects of these medications so important?
RICHARD ELION, MD: They're very important for a number of reasons. Number one, at the end of 12 to 13 months, anybody, any population taking HIV drugs, half the people fail. It's estimated that of the 50 percent who fail, perhaps as many as 70 or 80 percent of that group have failed because they just couldn't take the drugs. So clearly, if a drug is going to make a person not feel good or feel sick, they're not likely to take them. If you're taking a regimen twice a day and you miss one dose in one day, which is about a 95 percent rate. At that rate, below 95 percent, you can have as much as a 15 or 20 percent loss in efficacy. Therefore, adherence, being able to stay with this regimen is incredibly, fundamentally, cardinally important for success with these drugs.
The second reason side effects are very important is, we're trying to operate on a model that HIV is a long-term, treatable infection. If there is an incremental, small, step-by-step layering on of these side effects over time, if these drugs cause side effects, people won't be able to stay on them for years and years. If HIV were only a three- to five-year kind of crisis, then these side effects would be less important, but changes in body composition, changes in cholesterol, changes that change your risk factors for dying of heart disease or other things are very important to longevity, so those kind of toxicity profiles, combined with the difficulty of actually taking the meds due to the toxicity profiles, make the side effect aspect fundamentally important to the success of a regimen.
ANQUOINETTE CROSBY: Are certain side effects more difficult to cope with than others?
RICHARD ELION, MD: There are certain side effects that are difficult to cope with, and it's interesting that when physicians view what the side effects are, they're more difficult. In the patient's view, they don't always rank or order those issues the same. From the patient point of view, one of the key things is being able to take the drugs at convenient times, the ability to integrate it into your lifestyle and integrate it into your day. It's fundamentally important to being able to maintain these regimens.
I think the second thing is that the drugs can't make you feel sick. If they make you feel nauseous, if they cause you to have pain, if they do things to make you be aware that you're taking pills that are hurting you, unless you're extraordinarily motivated, you're not going to stay on that regimen.
ANQUOINETTE CROSBY: What can patients do to avoid these side effects and to deal with them when they do occur?
RICHARD ELION, MD: I think the most important thing patients can do to avoid side effects is, first of all, to have a positive partnership, a relationship with the caregiver, whoever that is, whereby their problems become something they can talk about. They don't feel it's just a hard thing being HIV-positive and they just have to take these drugs no matter what they do. Being able to have someone to talk to, see when the regimen can have changes made to see how you can combine food with certain of the pills to make the GI side effects less, to see which kind of vitamins might be beneficial to be taken alongside the regimen, to prevent the occurrence of certain side effects.
The other aspect that we try and do sometimes is to think ahead of what the potential side effects might be and give patients medication that might diminish or impair or even eliminate the risk of those side effects, to do that with patients who have GI problems. So we might give them medicine to help prevent diarrhea while they're taking those medicines so they can go about their day without remembering where every toilet is on their commute to work.
The other thing that frequently we'll do is if we find patients aren't tolerating the regimen or are tolerating it but are not happy with it, we'll try to switch them or transition them to a regimen that will be easier for them. That's one of the incidences where that communication between the provider and the patient is so important, because an experienced provider can just about always find a regimen that will be a fit for the patient, so really this is about trying to tailor that regimen to the individual's needs and their lifestyle.
ANQUOINETTE CROSBY: Dr. Boyle, how do help your patients avoid and deal with these side effects?
BRIAN BOYLE, MD: Routinely with my patients, I'll actually run through various regimens that are possible for them and talk about each component of the regimen, each individual antiretroviral agent, and sometimes patients outright say, "I don't like a medication that causes diarrhea, so I won't take that." So that knocks that medication out of the regimen, and we then move on, of course, if the patient has that option.
One of the keys, I think, to helping patients manage side effects encountered with antiretrovirals is preparation and education and having a plan, so that the patient's not blindsided by side effects when they occur, and then having the patient understand that if something unusual is encountered, or if something more than mild or moderate of the expected side effects is encountered, that they're to call their health care provider and discuss the side effects with them and discuss and decide on a plan for management of that.
ANQUOINETTE CROSBY: Dr. Elion, what is your final message to patients who are concerned with the side effects of NRTIs?
RICHARD ELION, MD: My final comment about side effects would relate to the fact that side effects are something that are inherent to any potential regimen, and the way to minimize and prevent these side effects is through good communication. Sometimes patients are afraid to tell the doctor about the problems they're having because they don't want to displease the expectations of the provider, the nurse or the doctor. This is the time for just frank honesty and intimacy in terms of what the problems are with your regimen, and by working as part of a partnership, I think most of these problems can be avoided.
ANQUOINETTE CROSBY: Final comments, Dr. Boyle?
BRIAN BOYLE, MD: Every medicine has side effects, so I think that's really the main point, and being prepared for the side effects and working with your health care provider to manage the side effects, I think, are the primary things that patients and health care providers need to focus upon, and recognizing that most medications, when you start them, can have some initial problems, and getting through that initial phase and into the later phases of taking the medication, where you may encounter no side effects, are probably the most important aspects of getting on antiretrovirals and staying on them.
ANQUOINETTE CROSBY: Doctors, thank you for joining us, and thank you for joining us on our webcast. I'm Anquoinette Crosby.
1 Comment
Here with me to talk about these side effects and what can be done to reduce them is Dr. Richard Elion, a physician in private practice in Washington, D.C. Thank you, doctor, for joining us. Also joining us from New York is Dr. Brian Boyle, Assistant Professor of Medicine at Weill Cornell Medical College.
Dr. Elion, what are the NRTIs, and how do they work?
RICHARD ELION, MD: NRTI is an acronym for nucleoside reverse transcriptase inhibitors, and those are the first class of drugs used for HIV. What they do is they prevent the RNA to be transcribed into DNA.
ANQUOINETTE CROSBY: What are some of the general side effects of the NRTIs?
RICHARD ELION, MD: Some of the general side effects of the NRTIs are, in combination with proteases, they seem to cause some changes in body composition, lipoatrophy and lipodeposition. In other words, the loss of fat and the deposition of fat. There are also some specific side effects -- anemia, some weakness of muscles, some neuropathy, some pancreatitis that's been associated with some of them, and those make up the majority of the side effects.
ANQUOINETTE CROSBY: Dr. Boyle, can you tell us how the side effects have interfered with your patients' adherence to treatments?
BRIAN BOYLE, MD: The side effects patients commonly encounter vary a lot, depending on which particular medications they're on. For example, AZT, also known as Retrovir, may have a lot of fatigue, may have some muscle aches, headaches and other symptoms. So I think that to say overall which side effects patients are going to have with antiretrovirals is relatively difficult, because it's going to vary a lot depending upon the individual medication, depending on how the medications are put together, and depending on the individual patient. Different patients have different side effects, depending upon the medications that they're on.
ANQUOINETTE CROSBY: Dr. Elion, why are the side effects of these medications so important?
RICHARD ELION, MD: They're very important for a number of reasons. Number one, at the end of 12 to 13 months, anybody, any population taking HIV drugs, half the people fail. It's estimated that of the 50 percent who fail, perhaps as many as 70 or 80 percent of that group have failed because they just couldn't take the drugs. So clearly, if a drug is going to make a person not feel good or feel sick, they're not likely to take them. If you're taking a regimen twice a day and you miss one dose in one day, which is about a 95 percent rate. At that rate, below 95 percent, you can have as much as a 15 or 20 percent loss in efficacy. Therefore, adherence, being able to stay with this regimen is incredibly, fundamentally, cardinally important for success with these drugs.
The second reason side effects are very important is, we're trying to operate on a model that HIV is a long-term, treatable infection. If there is an incremental, small, step-by-step layering on of these side effects over time, if these drugs cause side effects, people won't be able to stay on them for years and years. If HIV were only a three- to five-year kind of crisis, then these side effects would be less important, but changes in body composition, changes in cholesterol, changes that change your risk factors for dying of heart disease or other things are very important to longevity, so those kind of toxicity profiles, combined with the difficulty of actually taking the meds due to the toxicity profiles, make the side effect aspect fundamentally important to the success of a regimen.
ANQUOINETTE CROSBY: Are certain side effects more difficult to cope with than others?
RICHARD ELION, MD: There are certain side effects that are difficult to cope with, and it's interesting that when physicians view what the side effects are, they're more difficult. In the patient's view, they don't always rank or order those issues the same. From the patient point of view, one of the key things is being able to take the drugs at convenient times, the ability to integrate it into your lifestyle and integrate it into your day. It's fundamentally important to being able to maintain these regimens.
I think the second thing is that the drugs can't make you feel sick. If they make you feel nauseous, if they cause you to have pain, if they do things to make you be aware that you're taking pills that are hurting you, unless you're extraordinarily motivated, you're not going to stay on that regimen.
ANQUOINETTE CROSBY: What can patients do to avoid these side effects and to deal with them when they do occur?
RICHARD ELION, MD: I think the most important thing patients can do to avoid side effects is, first of all, to have a positive partnership, a relationship with the caregiver, whoever that is, whereby their problems become something they can talk about. They don't feel it's just a hard thing being HIV-positive and they just have to take these drugs no matter what they do. Being able to have someone to talk to, see when the regimen can have changes made to see how you can combine food with certain of the pills to make the GI side effects less, to see which kind of vitamins might be beneficial to be taken alongside the regimen, to prevent the occurrence of certain side effects.
The other aspect that we try and do sometimes is to think ahead of what the potential side effects might be and give patients medication that might diminish or impair or even eliminate the risk of those side effects, to do that with patients who have GI problems. So we might give them medicine to help prevent diarrhea while they're taking those medicines so they can go about their day without remembering where every toilet is on their commute to work.
The other thing that frequently we'll do is if we find patients aren't tolerating the regimen or are tolerating it but are not happy with it, we'll try to switch them or transition them to a regimen that will be easier for them. That's one of the incidences where that communication between the provider and the patient is so important, because an experienced provider can just about always find a regimen that will be a fit for the patient, so really this is about trying to tailor that regimen to the individual's needs and their lifestyle.
ANQUOINETTE CROSBY: Dr. Boyle, how do help your patients avoid and deal with these side effects?
BRIAN BOYLE, MD: Routinely with my patients, I'll actually run through various regimens that are possible for them and talk about each component of the regimen, each individual antiretroviral agent, and sometimes patients outright say, "I don't like a medication that causes diarrhea, so I won't take that." So that knocks that medication out of the regimen, and we then move on, of course, if the patient has that option.
One of the keys, I think, to helping patients manage side effects encountered with antiretrovirals is preparation and education and having a plan, so that the patient's not blindsided by side effects when they occur, and then having the patient understand that if something unusual is encountered, or if something more than mild or moderate of the expected side effects is encountered, that they're to call their health care provider and discuss the side effects with them and discuss and decide on a plan for management of that.
ANQUOINETTE CROSBY: Dr. Elion, what is your final message to patients who are concerned with the side effects of NRTIs?
RICHARD ELION, MD: My final comment about side effects would relate to the fact that side effects are something that are inherent to any potential regimen, and the way to minimize and prevent these side effects is through good communication. Sometimes patients are afraid to tell the doctor about the problems they're having because they don't want to displease the expectations of the provider, the nurse or the doctor. This is the time for just frank honesty and intimacy in terms of what the problems are with your regimen, and by working as part of a partnership, I think most of these problems can be avoided.
ANQUOINETTE CROSBY: Final comments, Dr. Boyle?
BRIAN BOYLE, MD: Every medicine has side effects, so I think that's really the main point, and being prepared for the side effects and working with your health care provider to manage the side effects, I think, are the primary things that patients and health care providers need to focus upon, and recognizing that most medications, when you start them, can have some initial problems, and getting through that initial phase and into the later phases of taking the medication, where you may encounter no side effects, are probably the most important aspects of getting on antiretrovirals and staying on them.
ANQUOINETTE CROSBY: Doctors, thank you for joining us, and thank you for joining us on our webcast. I'm Anquoinette Crosby.