Benefits and risks of treatment interruption

People who have been taking HIV therapy for a long time may wish to take breaks from treatment for several reasons. There are many potential reasons for treatment interruption, including:

• Taking a break without having to worry about drugs every day.
• Disruption of one’s schedule, for example due to travel.
• Relief of short-term side-effects.
• Prevention or resolution of long-term toxicities.
• Improved quality of life.
• Stimulation of the immune system to respond to HIV.
• Reversion to drug-sensitive wild-type virus.
• Delayed resistance and preservation of drugs for future use.
• Waiting for new and better drugs to become available.
• Decreased drug cost.

Likewise, treatment interruptions come with a variety of drawbacks or risks, including:

• Increased HIV replication and rising viral load.
• CD4 cell count decline.
• Clinical disease progression including opportunistic illnesses.
• Acute retroviral syndrome due to viral rebound.
• Liver enzyme flares if co-infected with hepatitis B.
• Possible higher risk of heart, liver and kidney problems.
• Emergence of further drug resistance.
• Higher risk of HIV transmission.
• Increased cost of medical care.

With current available antiretroviral therapies, there is every indication that treatment will probably have to continue for life. But ‘treatment fatigue’ is a common problem and many people wish to take breaks from pill-taking, even briefly. Others stop treatment for practical reasons, such as inability to obtain drugs due to lack of money or inadequate insurance coverage, disruption of normal routines or travel to countries where it might not be safe to carry HIV medications.

Perhaps the most common reason for treatment interruption is a desire to reduce the total duration of exposure to antiretroviral drugs, in the hope of reducing long-term toxicities such as mitochondrial or metabolic complications. Since these symptoms worsen progressively over time, it makes sense that a shorter period of drug exposure might mean fewer side-effects.

Whilst this approach seems logical, the SMART study (discussed below) showed that people who interrupted therapy had a higher risk of heart, liver and kidney problems that traditionally have been seen as signs of drug-related toxicity. Further, this and other recent studies have found that people who stop treatment do not necessarily enjoy an improved quality of life, suggesting that the benefits of treatment breaks may not be worth the risks.

A further consideration is the increased risk of HIV transmission through sex, mother-to-child transmission or sharing of injection drug equipment when a person has a high viral load. It is well known that the risk of sexual transmission is increased during acute HIV infection when people typically have a very high initial viral load; studies have also shown that mother-to-child transmission is more likely if a woman has unsuppressed virus. One case of HIV transmission has been reported in a discordant couple who stopped practising safe sex after the infected partner achieved an undetectable viral load, but then continued to have unprotected sex during a treatment interruption.¹