The Pharmaceutical Journal
Vol 268 No 7196 p597-604
4 May 2002

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Interruptions to HIV treatment might enhance viral replication

A study published in Nature has placed a question mark over the practice of structured treatment interruptions, or drug holidays, in patients infected with HIV (2002;417:95).

Researchers showed that HIV preferentially infects HIV-specific CD4 T cells. This enables the virus selectively to disable the specific immune response against it, thereby encouraging persistent infection in an otherwise immunocompetent host, they say. "The phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption."

The researchers studied the immune response in 12 HIV-infected individuals. They found that in all subjects, whether acutely or chronically infected, treated or untreated, HIV-specific CD4 T cells had been infected at a 2.1–5.3 times higher frequency than other CD4 T cells. When one subject stopped therapy, more than half the infected CD4 T cells were HIV-specific. This, say the researchers, suggests that it is the HIV-specific CD4 T-cell response that provides fuel for viral spreading.

Dr Daniel Douek, National Institutes of Health, Maryland, told The Journal that when therapy is stopped and virus is allowed to rebound, there is increased infection of all CD4 T cells, but a much greater increase in HIV-specific CD4 T cells. "Thus, by trying to boost the immune system with structured treatment interruptions, you might actually be causing some damage by infecting HIV-specific CD4 T cells and debilitating the anti-HIV response," he said.

Dr Douek added that a trial of short-course structured treatment interruptions — one week on therapy followed by one week off — is being conducted at NIH. Such courses do not allow virus to rebound and it is not expected that increased infection of HIV-specific CD4 T cells will occur. "So we must not tarnish all structured treatment interruptions with the same brush. Short-course structured treatment interruptions may have great value in helping to reduce drug-related side effects of therapy," he added.