Expert advisers to the World Health Organization have concluded that treatment programmes in resource-limited settings should prioritise a small number of second-line antiretroviral drugs, in order to make programmes simpler to run, to speed up drug approvals and to drive down costs of second-line drugs.
Following an expert meeting held last May, WHO will recommend that two nucleoside analogue backbones should be prioritised wherever possible: either tenofovir plus 3TC or FTC, or abacavir plus didanosine (ddI).
Two ritonavir-boosted protease inhibitors are favoured over others: either lopinavir or atazanavir. The chief reason for this choice is the price of the two drugs, which are substantially cheaper than any other protease inhibitors. The two drugs are also heat-stable, but atazanavir must be boosted with ritonavir, which is not available in a heat-stable form. The meeting report says that atazanavir is likely to be added to the UNITAID purchasing list for second-line thearpy in 2008.
“Doing so will create an incentive for generic manufacturers and possibly generic-originator partnerships to fast-track development of heat-stable versions of the product, either heat-stable RTV packaged with ATV, or heat-stable
fixed-dose combinations of ATV/r,” the report states.
The decision to slim down the range of second-line drug choices follows requests for advice from national treatment programmes concerned about the potentially large number of drugs they might need to approve and include in their national formularies. Clearer guidance on which drugs are likely to prove most effective after the failure of standard first-line regimens was also required.
A smaller range of drugs may also help drug regulators to decide which generic and branded products to prioritise for registration around the world, and may encourage the growth of demand for the products, which should feed through into lower prices eventually.
One of the surprises of the new guideline is the recommendation that 3TC – or FTC - should be recycled after the failure of first-line treatment. Although this strategy would not be endorsed in wealthy settings, experts agreed that where it is not possible to suppress viral load to undetectable levels, the presence of 3TC in the combination may nevertheless contribute some benefit, since several studies have now shown that despite high level 3TC resistance, treatment with the drug results in a viral load approximately 0.5log below the level seen in those who do not receive 3TC.