NIAID promote 7 day on-off HAART despite risks

Following trailers from Anthony Fauci which appeared as long ago as last summer’s Durban International AIDS Conference, researchers at the National Institute of Allergy and Infectious Diseases (NIAID) have published data from their pilot study investigating the effects of short-cycle, intermittent anti-HIV therapy.

NIAID researchers recruited 10 people whose viral load had been below 500 copies for at least six months, whilst taking a three or four drug HAART regimens. All ten had CD4 counts above 300 and viral load below 50 copies at the time of entry into the study. The study involved switching to a regimen of d4T/3TC/indinavir/ritonavir, which was taken for a week, followed by a week without drugs. This seven day on-off cycle was then continuously repeated throughout the study period. This ‘proof-of-concept’ study does not include a control arm.

Though it will require a much larger, randomised trial before firm conclusions can be drawn, during follow-up, there was no deterioration in control of HIV replication, no change in immune function, and an apparent reduction in some of the side-effects associated with anti-HIV medication.

Speaking about the study, which is published in the 4th December edition of the Proceedings of the National Academy of Science, lead investigator and report author Dr Mark Dybul said: “Because it halves the total time during which patients receive anti-HIV medication, structured intermittent therapy could significantly reduce the costs and side-effects of anti-HIV drugs.”

Critics of this approach argue that these attractive concepts remain unsubstantiated at the moment. Whilst reducing exposure to HAART will reduce drugs bills, it’s unclear how overall expenditure on care will change if additional monitoring is required, or indeed if treatment fails faster than would be expected for continuous treatment. Participants were on the trial for up to 88 weeks and viral load tests showed that viral replication was suppressed to below 50 copies in those who adhered to their medication schedule. However, the concern that regular changes to the therapy-taking routine may constitute an adherence barrier for some individuals appears to have been borne out in this experiment – two people were excluded from the trial for not taking their medication correctly.

Researchers also noted an improvement in some key side-effects associated with anti-HIV drugs. Cholesterol levels dropped by an average of 22% and triglyceride levels halved. Abnormal cholesterol and triglyceride levels are part of the lipodystrophy syndrome; an assortment of metabolic and body fat disturbances seen in people taking antiretrovirals.

Nevertheless, the NIAID team themselves acknowledge that this is a very small pilot study which cannot fully evaluate the potential role of structured treatment interruptions. And researchers are emphasising that cycling therapy is not something to try without strict medical supervision, as part of a clinical trial.

Criticism of the cycling method used by the NIAID has recently been voiced by Professor Andrew Phillips of the Royal Free and University College Medical School, London. In a modeling exercise he suggests that a seven day on, seven day off approach to therapy is a pattern of treatment interruption likely to favour the emergence of resistance.

In his article he argues that being on and off drugs for a short period of time (i.e. being off drugs for less time than that needed for viral load to return to pre-therapy levels), could lead to a situation where viruses with resistance mutations will have the optimum opportunity to infect target cells. Prof Phillips notes that the point at which viral load stabilises during treatment interruption is likely to indicate the point at which the supply of uninfected target cells is exhausted.