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 anti-HIV 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 T-cells – called HIV-specific T-cells – needed by the immune system to help control HIV. Very early on in the course of HIV infection, these HIV-specific T-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 anti-HIV 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 T-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 T-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.
Pregnancy
Anti-HIV treatment plays a major role in reducing the risk of mother-to-child HIV transmission. However, the use of anti-HIV 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 anti-HIV treatment (for example, their T-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 anti-HIV 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 anti-HIV treatment regimens – especially those with low T-cell counts – treatment interruptions may be dangerous. This was definitely the case in one study reported by a research team in Frankfurt, Germany. The study involved patients who had tried and failed several anti-HIV treatment regimens. Many of the patients who stopped therapy saw their T-cell counts fall very quickly, and some were diagnosed with a new AIDS-defining illness during the treatment interruption. The patients who remained on therapy, even though they had detectable viral loads, did not see their T-cell counts decrease by much and none were diagnosed with a new AIDS-related illness. Even though their anti-HIV treatment regimens weren't able to keep their viral loads undetectable, they were still able to protect the immune system and help ward off new illnesses.
Good viral load and T-cell responses to treatment
Most people who take anti-HIV drug treatment see their viral loads decrease and their T-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 T-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 T-cell counts. The results of two studies were reported in February 2006. In the Strategies for Management of Antiretroviral Therapy (SMART) study, approximately 5,500 people with T-cell counts above 350 were enrolled. They were 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 T4 count of 250 to restart patients on treatment.
Other treatment interruption approaches have been tried in patients who experience good viral load and T-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 T-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 T-cell counts above 450 (92% compared to 75% of people doing repeated treatment interruptions), the development of drug resistance was similar in both groups.
Search for news stories about this topic