Real Life Situations . . .

Protease Inhibitors vs. NNRTIs

Recently, there has been a lot of talk about switching from a protease inhibitor-based regimen to a non-nucleoside (NNRTI)-based regimen. Why is there so much interest in doing this? Should I consider switching to an NNRTI-based regimen?

ScalesInterest in switching from a protease inhibitor-based regimen to an NNRTI-based one is largely motivated by concerns about protease inhibitor side effects and about saving the protease inhibitors for later use when disease progression might require the strongest approach to treatment. With either approach, almost all such regimens include two NARTI (nucleoside analogue) drugs.

Generally NNRTIs have fewer side effects than protease inhibitors. Two big side effect concerns with protease inhibitors that often motivate switching therapy are fat redistribution resulting in a change in body shape composition (lipodystrophy) and abnormal changes in lab values, including triglycerides and cholesterol. This is seen in some people on long-term protease inhibitor therapy. However, it has still not been definitively shown that protease inhibitors are the cause or sole cause of lipodystrophy, nor is there any strong evidence that switching to an NNRTI-based regimen will correct the problem once it occurs.

A lot of research has looked at the effects of switching from protease inhibitor to NNRTI regimens on lipodystrophy. Some protease inhibitors, especially ritonavir, can significantly increase triglyceride and cholesterol levels that may increase the risk for heart disease. Study results so far suggest that changing regimens does not reverse fat redistribution, but triglyceride and cholesterol levels are decreased especially if the NNRTI is nevirapine (Viramune).

There are conflicting results on whether efavirenz (Sustiva) decreases these levels. So it might be reasonable to switch to an NNRTI-based regimen if your cholesterol and triglyceride levels are elevated. However, it is also possible to use cholesterol and triglyceride lowering drugs to achieve the same effect, although drug interactions may occur between these drugs and the protease inhibitors.

Another factor that leads some people to switch from protease inhibitor to NNRTI regimens is that most NNRTIs have relatively easy dosing. Fewer side effect and better ease of use lead some to believe that adherence (taking drugs as prescribed) will improve and thus increase the chances of long-term success.

The decision to change your anti-HIV regimen is best made in partnership with your doctor. Many experts believe that if you experience a good response (suppressed viral load and increases in CD4+ cell count) with minor or at least tolerable side effects on a protease inhibitor-based regimen, then it's reasonable and maybe even preferable to continue on that regimen. There is always a risk, whether from side effects or diminished response to therapy, with switching regimens.

A Note About NNRTIs

The dosing advantage of the NNRTIs has been diminished recently with the use of low dose (sometimes called baby dose) ritonavir (Norvir) in combination with another protease inhibitor. This results in higher and more sustained levels of the other protease inhibitor in the blood. Therefore it's possible to use lower doses of both drugs and the schedule can be reduced to twice-a-day and possibly even once daily. However, this combination may not be an option for everybody.

Opportunistic Infections

My doctor recently told me that I can stop taking my opportunistic infections (OI) preventive therapies. Does this mean that I can also stop taking my anti-HIV drugs?

It's likely that your doctor told you that it is safe to stop taking your OI preventive medicine because you have had a sustained increase in CD4+ cell counts from being on effective anti-HIV therapies. If this were the reason, it would be unwise to stop taking your anti-HIV therapies as they are making your immune system stronger and able to ward off disease-causing organisms without the need of more drugs.

However, there could be other reasons why your doctor suggests that you go off certain medications, including concerns about drug interactions or side effects. Talk to your doctor to find out why she or he is encouraging you to stop taking any therapy.

The US Public Health Service has issued guidelines on when it may be safe to stop taking preventive OI therapies. For more information on these federal guidelines, read PI Perspective 28.

Side Effects

I am considering stopping my anti-HIV therapies because of side effects. Does this sound reasonable? I have also heard that I might develop resistance to these therapies if I stop them. Is there anything I can do to reduce the risk of developing resistance? How long should I stop for and when I restart therapy should I use the same regimen or a different one?

Dealing with drug side effects can be a real challenge. Most are treatable, either by switching a particular drug or by using ways to treat or manage the side effect. So the first response might best be exploring ways to treat or manage them, not to immediately stop your anti-HIV drugs.

WomanIt's important to remember that lots of people experience side effects for about a month or two after they start or switch to a new regimen. They usually decrease over time as your body adjusts to the drugs. However, if they continue for more than two months or get more severe over time, contact your doctor immediately.

Stopping anti-HIV therapies is one way to deal with serious side effects, but that decision is best made with your doctor. When you talk to your doctor, remember that there are potential concerns, including: a drop in CD4+ cell counts (in some people this can be quite dramatic); an increase in viral load; and a small but real possibility of developing resistance to one or more drugs in your regimen.

Resistance is not always well understood. The only time we're certain that someone won't develop resistance is when they're off treatment. There's some evidence that going off treatment for awhile tends to reverse some of the resistance a person has already built up.

Does this mean that there's no chance of developing resistance from going off therapy? Not exactly. Even though there's little or no evidence of developing resistance after stopping therapy, there is still a theoretical concern -- especially if you go on and off therapy several times.

Each time treatment is stopped and later restarted, it creates a brief period when there's an inadequate level of drug in the bloodstream. In theory, these periods are brief "windows of opportunity" for developing resistance.

To minimize this risk, it's important to not simply stop taking one drug in your regimen or to reduce the dose of a drug without guidance from your doctor.

If you choose to stop therapy, there is some slowly emerging information to help guide doing that more safely. Some experts suggest that people using nevirapine (Viramune) or efavirenz (Sustiva) stop those drugs two or three days before stopping other anti-HIV medications. This is because these two drugs remain in the blood much longer than other drugs. Consequently, if you stop all the anti-HIV drugs at the same time, nevirapine or efavirenz will be found in the blood after the others have worn off. This might increase the risk of developing resistance to either one. Ideally, the blood levels of all anti-HIV drugs should reach zero at about the same time.

Unfortunately, there is no good answer to how long someone should stop their anti-HIV drugs. We do know that after stopping therapy, it becomes even more important to closely monitor your CD4+ cell counts and viral load to help guide future decisions.

Finally, many factors need to be considered when restarting anti-HIV therapy. If the side effect(s) went away while you were off therapy, it's likely that one or more drugs caused the side effect(s). Restarting the same regimen may not be wise as those side effect(s) may reappear. This is not always the case, but switching to another regimen is probably preferable.

Another consideration is whether you could switch to a whole new regimen. If not, it's even more important to identify the drug causing the side effect and substitute it. It may also benefit you to take a resistance test before stopping the original regimen to help select a new one. Just remember, a resistance test can only be accurately done if you have a viral load above 1,000 copies/mL.

Tried and True vs. Brand Spanking New

Should I switch to a new (recently approved/available) anti-HIV drug right now? Are new anti-HIV drugs better than old ones?

As more anti-HIV drugs are developed, many wonder if they should switch to a newer drug. A new drug isn't necessarily better or worse than older ones. To decide if switching to a new drug is right for you, start by evaluating new the same way you evaluate old.

Collect and consider the available information about potency, drug interactions, reported side effects and dosing schedule. Remember that while a new drug often sounds good -- especially amid the hype of marketing campaigns -- it may not be the one for you. Think strategically about your future options and plan for the long-term before you switch.

Perhaps most importantly, think about your reasons for changing. If you're currently doing well and have minimal side effects, changing might not be wise. You would be stepping off into the unknown, while abandoning something that's working well for you. On the other hand, if you're experiencing some level of drug failure, adherence problems or serious side effects, it would be wise to consider a change.

That said, a new drug may (or not) be more potent than the current drugs -- maybe even against resistant virus. If it is, this is good news for those who have taken many anti-HIV drugs and are "treatment experienced." A new drug might be easier to take -- with once a day dosing, for example. This can lead to improved adherence. Also, it could claim fewer or more tolerable side effects overall, making it an attractive option for those struggling with side effects.

There is sometimes a psychological boost from taking something new. Because few people have taken the drug, there's little negative news about it, which makes people feel good. Feeling good and hopeful about treatment can lead to better adherence and health in general.

On the other hand, a new drug has often only been used by a small number of people for a limited time. This means that some of the information about the drug may not be apparent until more people, like you, use it. We have less information about a new drug than almost any older drug. And six months or a year from now, we will know more about it than we do today.

Also, doctors generally have less experience with a new drug, and so they aren't used to recognizing its potential side effects. New can also mean that side effects aren't well characterized yet. This might worsen quality of life and interfere with the ability to adhere. However, this is not unique to a new drug. It's a risk associated with switching in general.

Most people, rather than jumping on the new drug bandwagon, will wait until more doctors and patients have used the drug and experienced and managed side effects, so that when they are ready to make a switch there's more information to consider. Ultimately, the key to switching to a new drug or an older one is strategy: don't switch without a reason for doing so, and if you do, don't plan only for the short-term but for a long and healthy treatment future.


I just found out I am seven weeks pregnant. Is it true that I shouldn't take any anti-HIV medications during the first trimester?

Pregnant womanThe first trimester (14 weeks) of pregnancy is a time of great physical change for a woman and her developing baby. There are two main reasons why some doctors and women prefer to delay starting anti-HIV treatment during this time. One is the concern about side effects to the developing baby, and the second is the difficulty that starting therapy poses to a newly pregnant woman whose body is undergoing great change.

First, the beginning trimester is the time when the baby's organs, like the heart, lungs and brain, develop most rapidly and are especially fragile. The developing baby may be prone to harm from any drugs that the mother takes. So, some women may prefer to delay treatment until after the first trimester, when the baby's organ development is completed.

Some women taking anti-HIV drugs when they find out they're pregnant may switch or stop certain ones during the first trimester. Switching to those less likely to harm the baby is common. Stopping altogether, however, should be done with great care as the drugs may help maintain the mother's health during this important time.

Second, many women experience morning sickness during the first trimester. These symptoms may worsen with therapy, making taking drugs as prescribed difficult. This may result in decreased drug levels in the blood, increasing the risk of drug resistance. So, delaying treatment may lessen these uncomfortable symptoms and prevent problems linked to poor adherence like developing drug resistance.

No woman should ever be denied treatment or forced to stop taking anti-HIV medications during the first trimester. Using therapy during this time should really depend on her own health needs and personal preferences. Understanding the risks and benefits associated with delaying, stopping or continuing medications during the first trimester is critical.

Lastly, anti-HIV medications help reduce mother-to-child HIV transmission. Anti-HIV therapies are only one part of a bigger picture of mother-to-child HIV prevention. Good prenatal care and stable support along with careful attention to the health and nutrition of the expectant mother are equally important.

For more information on HIV and pregnancy, read Project Inform's Pregnancy and HIV.

Back to the Project Inform WISE Words March 2001 contents page.