Immune stimulation by treatment interruption

Intermittent therapy has been investigated as a means of stimulating the body’s HIV-specific immune responses. In order to mount an effective response, immune cells must be able to recognise a disease-causing organism, which cannot happen when HIV is fully suppressed. The theory was that stopping treatment and allowing viral load to rise from time to time might have the effect of ‘autovaccination’, encouraging the immune system to step up its activity against the virus.

Several studies have looked at structured treatment interruption after starting antiretroviral therapy during acute or primary infection. During the earliest stages of infection, the immune system generates CD4 and CD8 T-cells designed to respond to HIV, but in most people this is not adequate to keep the virus under control. Studies of treatment interruption during or after primary HIV infection have yielded mixed results, but on the whole treatment breaks do not appear to help the immune system control HIV over the long term. For further discussion, see Starting HIV treatment: Treatment during primary infection.

As for treatment interruptions once HIV infection is established, early research produced some promising results, but most studies have failed to show any consistent effect on HIV-specific immune responses, CD4 cell counts, viral load set-point or speed of viral rebound after stopping therapy.

For example, the Swiss-Spanish Intermittent Treatment Trial found that cycles of structured treatment interruption had no effect on viral load. The study enrolled 133 individuals with an undetectable viral load, a CD4 cell count of at least 300 cells/mm³ and no prior treatment failures. Participants interrupted treatment for two weeks then recommenced therapy for eight weeks in four cycles, provided that viral load stayed below 50 copies/ml. Treatment was then stopped indefinitely at week 40. By week 52, only 17% had a viral load below 5000 copies/ml, dropping to 8% by 96 weeks. Although HIV-specific CD8 cell counts did increase, this did not enable control of the virus.¹

On the whole, studies generally have not demonstrated that allowing virus levels to rise periodically improves immune response during chronic infection. Most people’s immune systems are not able to effectively control HIV when they are not taking any antiretroviral treatment at all, so it is not clear how higher virus levels during a treatment break might be helpful.