Glasgow conference confirms swing to later treatment

US treatment guidelines will soon shift towards the more cautious approach favoured in the UK, Paul Volberding told the Fifth International Congress on Drug Therapy in HIV Infection yesterday in Glasgow. US treatment guidelines currently encourage physicians and patients to consider starting treatment if an individual’s CD4 cell count falls below 500 accompanied by a viral load above 10-20,000 copies. In contrast the British HIV Association guidelines suggest that treatment should be deferred until the CD4 cell count falls below 350 and viral load has risen above 30,000 – 50,000 copies.

Outlining the principles likely to be reflected in revised International AIDS Society guidelines – and mirrored in US Department of Health and Human Services guidelines also under revision, Dr Volberding stated the new paradigm of treatment after four years’ experience of HAART:

• Treat at a CD4 cell count below 200, or when symptoms develop, whichever occurs earlier

• When the CD4 cell count lies between 200 and 500, the primary trigger for choosing when to start treatment should be the CD4 cell count, not viral load

• The primary value of knowing the viral load level is to determine how frequently the CD4 cell count should be measured – if viral load is high, measure the CD4 cell count more often

• Assuming that the first regimen will be the most durable, and therefore used for longer than any subsequent regimen, the key question in determining which drugs to use should be: which regimen will cause least long-term toxicity?

However, in a plenary address to the conference, Scott Hammer of Columbia University and the US AIDS Clinical Trials Group said that he believed the pendulum would swing back towards earlier treatment.

“A more aggressive stance will re-emerge onto the scene, I think, as drugs improve. When simple, potent, durable, non-toxic regimens become the norm, the pendulum will swing back towards aggressive early therapy”, he said.

The guideline changes are supported by data presented today by the Royal Free Hospital and University College Medical School team, which show no difference in the likelihood of viral suppression after 32 weeks on treatment between people who started HAART at CD4 counts between 200 and 350, and those who started HAART with CD4 counts above 350. The groups also found that the risk of viral rebound after initial suppression below 500 copies was not affected by the baseline viral load at which individuals started treatment, strongly rebutting the view that HAART will be more durable if started at a lower viral load level (e.g. less than 30,000 copies).

Prof. Andrew Phillips analysed data from three European cohorts of individuals who started HAART, and found that amongst 2742 individuals, only those with CD4 cell counts below 200 had a poorer response to therapy (defined as failure to achieve viral load below 500 copies within 32 weeks). Similarly, only those with viral load above 100,000 copies had a poorer response to therapy.

Alessandro Cozzi-Lepri analysed data from 1484 Italian patients in the ICONA cohort who started HAART in the year beginning May 1997, and found no difference in the size of the CD4 cell increase after 96 weeks when comparing the immunological response in those with CD4 cell counts below 200, between 201 and 350, and above 350 at baseline. There was no significant difference in the risk of viral load rebound after week 32 between those started therapy when their CD4 cell counts were between 201 and 350, and those above 350, but those who started therapy with a CD4 count below 200 did have a higher risk of rebound.

British HIV Association guidelines will be updated in the first quarter of 2001, but asked whether he thought British guidelines ought to recommend a lower starting point than a CD4 count of 350, Professor Brian Gazzard, Chair of BHIVA, said yesterday that he did not expect major changes to British guidance.

“I would not feel comfortable with a starting point below 300, given the risk of illness in patients [with fast CD4 cell declines]. I think these findings broadly confirm that we were right to set the starting point at around 350-300”, he told aidsmap.