Antiretroviral treatment is a long-term commitment. For most people with HIV, once treatment is started, it must be continued indefinitely, being careful to take all of the medications exactly as prescribed. This, however, is easier said than done.

There are occasions in which treatment needs to be stopped temporarily, and there are important issues to remember when doing this. Even if treatment interruptions aren't necessary, they may be desirable, given that antiretroviral treatment can cause long-term side effects, can be difficult to adhere to on a daily basis, and can be costly. Because of these and other challenges, there has been a lot of interest in the study of treatment interruptions, also known as "structured treatment interruptions" (STIs) and "drug holidays."

While treatment interruptions may have a number of possible benefits, they are only supported for certain HIV-positive people receiving antiretroviral treatment. If you are considering a treatment interruption, be sure to talk with your healthcare provider about the information contained here. Under no circumstances should you attempt a treatment interruption on your own, without direct supervision from your healthcare provider. Treatment interruptions are still considered to be highly experimental and potentially dangerous.

Are treatment interruptions ever necessary?
According to most HIV experts—as well as HIV treatment guidelines published by the U.S. Department for Health and Human Services (DHHS) and the International AIDS Society-USA (IAS-USA)—once antiretroviral treatment becomes necessary, it should be continued indefinitely. However, there are a number of circumstances that can arise while someone is on antiretroviral treatment that may require him or her to temporarily stop therapy. These include:

  • Side effects and drug toxicities that require treatment to be stopped.
  • Other illnesses that can increase the risk of side effects or make it difficult for people to swallow or absorb oral medications.
  • Travel restrictions. For some travelers, packing and taking HIV medications while away from home can be a difficult situation. For example, some countries prohibit the entry of HIV-positive citizens from other countries (fortunately, this is no longer an issue for people living with HIV planning on visiting the United States). While it is not recommended, temporarily stopping treatment to avoid being identified as HIV positive while traveling internationally is sometimes necessary.
  • Surgery that requires nothing be taken by mouth (such as liquids, food, or pills) 12 hours before the procedure, or surgery that may not allow someone to swallow medications after the procedure is completed.
  • Non-availability of drugs, such as running out of medication before a refill prescription can be filled.
  • Participation in a clinical trial. As researchers continue looking at ways to cure HIV, including gene therapies and immune-based therapies like therapeutic vaccines, people living with HIV participating in studies of these experimental approaches may be asked to temporarily discontinue their HIV treatment. Seeing what happens to the virus and the immune system in the absence of standard HIV treatment, but after receiving a medication designed to help eradicate the virus from the body, will be essential to this research.

When treatment must be stopped immediately, it is best to discontinue all of the drugs at the same time. However, if a necessary treatment interruption can be planned in advance—such as elective surgery or travel restrictions—there are a few important issues to consider:

  • Are you using Sustiva (efavirenz) or Viramune (nevirapine)? If you are considering a treatment interruption and are taking either of these drugs, it is best to plan ahead. This is because these drugs stay in the blood much longer than protease inhibitors (PIs) or nucleoside reverse transcriptase inhibitors (NRTIs). For example, if someone stops their Sustiva and two nucleoside analogues on the same day, the Sustiva will linger in the body longer than the either of the nucleoside analogues. This would be like taking only the Sustiva without the addition of other antiretroviral treatments, which can cause the virus to become resistant to the Sustiva. As a result, people who are taking a break from their Sustiva- or Viramune-based combination should consider stopping the Sustiva or Viramune at least a few days or a week (up to three weeks) before stopping the other antiretroviral drugs they are taking. Unfortunately, research hasn't yet determined the best time to stop either of these drugs if a treatment interruption is necessary. If you've been off of your Viramune-based regimen for two weeks or longer, you should be careful upon restarting the drug. Like starting Viramune for the first time, it is best to restart the Viramune using half the recommended daily dose (200mg once daily), continue it for 14 days, and then start taking the full daily dose again (200mg twice daily).
  • Are you taking HIV medications that need to be taken with food? If you are not taking a regimen that contains Sustiva or Viramune but are taking medications that need to be taken with food, it is best to stop all of the medications at the same time. If you are stopping because of surgery, schedule your last dose for 12 hours before the procedure—the last time you will be able to eat anything before the surgery. You should resume taking all of your antiretroviral medications as soon as you're allowed to eat and drink again.
  • Are you taking HIV medications that do not need to be taken with food? If you are not taking a regimen that contains Sustiva or Viramune but are taking medications that do not need to be taken with food, it is best to stop all of the medications at the same time. Alternatively, take your medications as scheduled with a sip of water. If treatment is interrupted, all drugs should be restarted together.

People who have HIV and hepatitis B must also be careful with treatment interruptions. If you have chronic hepatitis B and are taking Epivir (lamivudine), Emtriva (emtricitabine), Viread (tenofovir), Combivir (zidovudine/lamivudine), Truvada (tenofovir/emtricitabine), Epzicom (abacavir/lamivudine), Trizivir (abacavir/zidovudine/lamivudine), or Atripla (efavirenz/tenofovir/emtricitabine), abruptly stopping any of these drugs may cause a "hepatic flare" – a sudden and sharp increase in liver enzymes and damage to the liver. If you have HIV and hepatitis B and need to temporarily stop any of these drugs, your doctor should monitor your liver enzymes very careful, at least until therapy is restarted.

Above all, a decision to temporarily stop treatment should be made in consultation with a healthcare professional.

What about other types of treatment interruptions?
Beyond acute situations that may require someone to temporarily stop therapy, treatment interruptions have been explored in clinical trials for a variety of reasons. On a practical level, treatment interruptions may help to reduce overall treatment cost, limit the inconvenience of daily medications, and potentially reduce the risk of long-term side effects. Treatment interruptions have also been studied as a way to boost the immune system and to help people who have tried and failed numerous antiretroviral drugs in the past respond better to "salvage" drug regimens. Here's a look at some of the experimental treatment approaches that have been explored in clinical trials:

Immune system boost
It has been suggested that treatment interruptions can be used to boost the activity of certain CD4 cells—called HIV-specific CD4 cells—needed by the immune system to help control HIV. Very early on in the course of HIV infection, these HIV-specific CD4 cells are quickly overcome by the large amount of virus in the body. In turn, the immune system is unable to mount the necessary response needed to control the infection. Once antiretroviral treatment is started, there is often a rapid and dramatic reduction in the amount of virus in the body – so much so that the immune system quickly forgets that the virus is present. As a result, the immune system doesn't perceive HIV to be a threat and doesn't attempt to mount the necessary immune response against the virus. Researchers have studied treatment interruptions as a way to control the amount of virus circulating in the body—allowing for enough virus to spark HIV-specific CD4 cell components of the immune system, but not enough virus to overwhelm the immune system.

This theory has been tested in people who began treatment within a few months after they were infected with the virus. These patients are said to have "primary HIV infection," as they are usually diagnosed with HIV while they have symptoms of infection and do not yet have antibodies to the virus in their bloodstream. Because these people started therapy so quickly after becoming infected with HIV, it is possible that their immune systems are better equipped to successfully control HIV in response to treatment interruptions. While some studies involving patients with primary HIV infection who received immediate treatment have demonstrated short-term benefits associated with treatment interruptions, almost all patients eventually saw their viral loads increase and CD4 cell counts decrease.

Researchers have also concluded that treatment interruptions are not an effective way to boost the HIV-fighting capabilities of the immune system in people who are said to have "chronic HIV infection." Generally speaking, these are people who have been infected with HIV for at least a year. While some studies have suggested that treatment interruptions were beneficial for some patients who started therapy after they had been infected for more than a year, several other studies were not able to confirm these results.

Antiretroviral treatment plays a major role in reducing the risk of mother-to-child HIV transmission. However, the use of antiretroviral treatment during pregnancy is not always straightforward.

For starters, pregnant women may want to temporarily stop treatment in early pregnancy because of nausea and vomiting. They may also be concerned about information suggesting that some prescription and over-the-counter drugs can cause fetal damage during the first three months (first trimester) of pregnancy.

Additionally, many pregnant women may not yet meet the requirements for starting antiretroviral treatment (for example, their CD4 cell counts are above 350). However, in order to reduce the risk of transmitting the virus to their babies, a combination of drugs will need to be started. In this situation, therapy is routinely stopped after delivery.

All of the issues raised in the "Necessary Treatment Interruptions" section of this lesson should be considered when stopping treatment during or after pregnancy.

Treatment failure
There are a growing number of HIV-infected people who have been on several antiretroviral treatment combinations and are unable to keep their viral loads undetectable. Researchers have theorized that temporarily stopping therapy might help their virus switch to a strain that is sensitive to the drugs, much like it was before therapy was started in the first place. This, in turn, might increase the chance of reducing viral load—and keeping it undetectable—upon starting a "salvage" drug regimen.

Unfortunately, clinical trials evaluating this theory did not produce encouraging results. In fact, for patients who have tried and failed several antiretroviral treatment regimens—especially those with low CD4-cell counts—treatment interruptions may be dangerous. Even though treatment regimens may not be able to keep viral loads undetectable, they can still protect the immune system and help ward off new illnesses.

Good viral load and C4D-cell responses to treatment
Most people who take antiretrovirals see their viral loads decrease and their CD4-cell counts increase, often to levels that are comparable to those seen in HIV-negative people. In turn, researchers have looked at the possibility of treating HIV like other chronic diseases: starting therapy when the immune system shows signs of damage or when somebody experiences symptoms of HIV diseases, stopping it when their health improves, and restarting treatment when the CD-cell count falls again (and so on).

Several clinical trials have been conducted to determine the safety of such treatment interruptions, in which the decision to stop and restart therapy is determined using CD4-cell counts. In the Strategies for Management of Antiretroviral Therapy (SMART) study, people with CD4 cell counts above 350 were enrolled and randomized to one of two groups: a continuous treatment group that did not stop HIV treatment, or a treatment interruption group that stopped treatment when the CD4 count rose above 350, restarted when the CD4 count dropped below 250, stopped again when it rose above 350, and so on.

The study was supposed to continue for approximately nine years, but was stopped after 14 months due to worrisome results. Early data indicated that patients in the treatment interruption group had an increased risk of disease progression and death, compared to patients in the continuous treatment group. The SMART researchers were hoping that patients in the treatment interruption group would experience fewer complications that can be caused by HIV treatment, such as heart attacks, stroke, coronary artery disease, kidney problems, and liver damage. But they actually found more complications in the treatment interruption group.

Similar studies produced conflicting results. For example, in the STACCATO trial, people doing STIs who restarted treatment at a higher T4 count – 350, compared to SMART's 250 – were no more likely to die or experience an AIDS-related complication, compared to those who remained on continuous therapy. But another study, the TRIVACAN study, mirrored the results of SMART. It, too, used a CD4 count of 250 to restart patients on treatment.

Other treatment interruption approaches have been tried in patients who experience good viral load and CD4-cell count responses to treatment. For example, some studies have looked at using weekly and monthly time frames instead. For example, the Italian ISS PART study compared 137 people on continuous therapy to 136 people doing increasingly long treatment interruptions (of one, two and three months, each followed by three months on treatment), and had positive results: while the treatment interruption group had a slight drop in CD4 cell counts after two years, 91% of the treatment interruption group and 92% of the continuous treatment group had viral loads below 400. There was also the French WINDOWS study comparing continuous treatment to a two-months-on, two-months-off treatment interruption approach in 403 people. After 21 months, there were no AIDS-defining events in either group. While more people in the continuous treatment group had CD4 cell counts above 450 (92% compared to 75% of people doing repeated treatment interruptions), the development of drug resistance was similar in both groups.

In the end, as often happens with studies that are designed to give a "final answer" to a major question, the conclusions of these studies yield even more questions than answers. For the near future, the message for people with HIV who want to take a break from their meds remains the same: treatment interruptions are risky and should not be attempted without a careful evaluation of the possible risks and benefits, and certainly not without the guidance of an HIV expert or within a clinical trial.

Last Revised: February 14, 2016