Some patients may wish to stop their HIV therapy temporarily for personal or social reasons. These include:

• Side-effects.
• Treatment fatigue and desire for a break.
• Problems with adherence.
• Travel or disruption to usual routine.
• Success of treatment or high CD4 cell count.
• Cost of medications and associated healthcare.

An analysis of 8300 European HIV-positive patients recently found that 16% interrupted HIV treatment for at least two weeks during the first two years of treatment. This was more likely in women, in patients with high viral loads before starting treatment, and those with a poor response to anti-HIV therapy^[1].

In addition to reducing exposure to anti-HIV drugs, there may be other health benefits associated with stopping or cycling therapy. Researchers are currently investigating the extent to which:

• Interruptions reduce the presence of drug-resistant virus before switching therapy.
• Cycling therapy stimulates the body’s own immune responses to HIV.
• Cycling therapy plus treatment with immune-based therapies stimulate the body’s own immune responses to HIV.
• Cycling therapy during the early stages of HIV infection may alter or slow the overall course of the disease.

The other reason for a treatment interruption is starting therapy unnecessarily early in the first place. In the late 1990s, many people commenced antiretroviral treatment before they had experienced much immune damage. Since that time, several studies have found that starting treatment before the CD4 cell count falls below 350 cells/mm³ provides no health benefit. As a result, treatment guidelines have become more conservative. This trend away from early therapy and the prevalence of long-term side-effects associated with anti-HIV drugs have led many patients and their doctors to consider stopping therapy.

The debate: continuous versus intermittent therapy

The disparity between the ‘ideal’ of life-long treatment and the reality of intermittent therapy was first highlighted at the 2000 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), which heard during an interactive session that more than one-third of North American physicians had already managed a patient who had undertaken a structured treatment interruption. In addition, 58% had encountered at least one patient who wanted to try a structured treatment interruption. Subsequent studies have demonstrated that some people had simply been taking themselves off therapy when their immune systems have been restored, or because of side-effects^[2][3].

The debate around continuous versus intermittent therapy rests on an assessment of the risks and benefits of each strategy.

Advocates of continuous therapy emphasise benefits such as slow immune restoration and the rebuilding of damaged lymph nodes that occur during long-term antiretroviral therapy. However, the ongoing benefits of antiretroviral therapy in terms of CD4 cell count increases and viral load reductions slow over time. After three years of continuous treatment, the ongoing benefits to the immune system are minimal although, of course, continuous therapy protects against the immune damage that occurs in the absence of therapy.

The immune damage that follows treatment interruption is of major importance to continuous therapy advocates. They are wary of potential and dramatic immune damage when therapy is stopped, particularly in people who previously had low CD4 cell counts.

However, others are more circumspect, acknowledging that continuous therapy would likely last for many years because the lifespan of HIV-infected people has been extended considerably by combination therapy. This group accepts that life-long therapy may not be such a good idea due to severe long-term side-effects, such as body fat changes, elevated blood fats, diabetes, heart disease and liver damage, and the increased risk of drug resistance as adherence to therapy wanes. There is some evidence that stopping therapy can alleviate some of these side-effects, such as the blood fat changes that occur during antiretroviral therapy.

A systematic review of studies into structured treatment interruptions published in 2005 concluded that timed interruptions put patients at risk of developing drug resistance, without any significant immunological or virological benefits or reductions in side-effects^[4]. The review also concluded that CD4 cell count-guided treatment interruptions were probably safe in the short term, but acknowledged that longer-term safety had not been examined. However, the discovery of the risks of this approach in early 2006 have also called the safety of this approach into question.