Boosting the Immune System

An effective HAART cocktail can almost completely shut down HIV replication. With medication controlling the virus, the immune system can start to rebuild itself. However, with almost no virus in circulation to keep them on their guard, immune cells don't always recognize that the enemy is still there, so the natural anti-HIV response may fade. When treatment is stopped, the virus will replicate freely, and immune cells will be exposed to it once again. In theory, structured treatment interruptions (STIs) might, therefore, encourage the immune system to control HIV. Researchers studying this have theorized that after each interruption of therapy, the body's ability to control HIV might increase, ultimately allowing drug therapy to be stopped.

This theory has been tested in several clinical trials and the results have been quite different depending on the disease stage in which the interruption of therapy is begun. Improvement of immune responses has definitely been seen in some people doing STIs during the acute HIV infection stage (immediately after initial infection). The trials have not been ongoing for long enough to know how long-lasting the improved viral control will be or the ultimate clinical benefit to the trial participants, but for now some researchers are encouraged by the results they've seen. However, the same cannot be said for the results so far seen with attempts to boost immune control of the virus in those in later disease stages (the "chronically infected"). Most people with longer-term infection who stopped their treatment had a very rapid rise in their viral loads and had to start their cocktails again. Even with multiple repetitions of the STIs, most PHAs have been unable to regain sufficient immune control to discontinue drug therapy for a lengthy period. Researchers are now considering the possibility that for those with chronic infection, a combination of STIs with therapeutic vaccines that are aimed at further boosting the immune response to HIV might have a better effect. Clinical trials to assess this possibility are ongoing.

To Make Drug-Resistant Virus Sensitive to Treatment

Many people who have used multiple anti-HIV drugs for lengthy periods have virus that is resistant to most or all of the current drugs. Taking a break from treatment would mean that the virus in their bodies would no longer be under pressure from the drugs. As a result, drug-sensitive virus (also called "wildtype") is able to replicate. After a few months without treatment, most of the virus will again be "wildtype," as wildtype usually replicates faster than drug-resistant virus. This could mean that such people could start treatment again, even with drugs they've previously used. Because much of the virus in their bodies is once again sensitive to the effects of the drugs, they may get good control of their HIV for at least some period of time. Unfortunately, in the research done to date, it appears that this effect may only last for a few months in some HIV positive people. Eventually, the drug-resistant virus, which had faded away but not completely disappeared, may return in some people.

To Improve Quality of Life

Sometimes a drug holiday can improve your quality of life. Side effects and toxicities, high numbers of pills, difficulties in sticking to the drug schedule over time, treatment as a constant reminder of HIV infection, and simply being tired of downing the drugs every day can make taking a break look very attractive. Taking a drug holiday may also reduce the risk of long-term complications of the drugs.

There are many concerns that have been expressed about the possible negative results of interrupting therapy. The most-often mentioned is the fear that going on and off drugs could create resistance. However, it appears so far that in people whose virus is fully suppressed -- meaning that their viral load is undetectable -- there may not be much risk of resistance.

It's simply a matter of the biology of resistance. The viral mutations that can create resistance occur as a function of viral load -- the more viruses that are present, the more chances there are for one of them to accidentally develop a mutation that allows it to resist a drug's antiretroviral effect. Then, since it's not being affected by the drug, it can replicate and eventually become the dominant population of HIV in the body. This is particularly likely when low drug levels are present (because someone is skipping doses or not taking drugs as directed or because an unexpected drug interaction lowers HAART medication levels).

With a planned therapy interruption, the drugs are taken properly during the treatment interval, and then stopped cold turkey. Thus, the low drug levels that would be problematic are not present except for a very brief interlude immediately following the cessation (stopping). If the virus is fully suppressed prior to the drug cessation, that means that there should be very little chance of developing resistance to the drugs. This also means that when the virus reappears during the drug holiday, the re-populating virus should be wild-type and sensitive to most drugs. Data from the STI studies so far done suggest that this is, indeed, the case in people with undetectable viral loads prior to a treatment interruption.

In the beginning there was a great deal of excitement about the possibilities for structured treatment interruptions. Disappointing results from more recent studies, however, have tempered this enthusiasm.