Protease inhibitors, the backbone of many HIV treatment regimes, may select different patterns of resistance in the strains of HIV most common in southern Africa (sub type C) and Europe (subtype B). In particular, patients with subtype C who receive treatment with nelfinavir are much less likely to develop a mutation that allows other protease inhibitors to be used if nelfinavir fails.
A study presented by Dr Pat Cane, of Birmingham's Public Health Laboratory indicated that the protease gene in subtype C of HIV mutated in significantly different ways to subtype B of the virus. Subtype B is most prevalent form of HIV in the UK, North America and the rest of the industrialised world, and was accordingly the strain of the virus which all the currently licensed protease inhibitors were developed to fight.
However, subtype c is the most widespread type of the virus worldwide, with particular concentrations in southern Africa, and increasing numbers of cases of subtype C are being detected in the UK, particularly amongst heterosexuals.
Dr Cane's study found that the pattern of major mutations, which can confer resistance to some or all drugs, in people whose treatment was failing differed from those seen in subtype B.
In particular, the incidence of the D30N mutation associated with the failure of nelfinavir treatment was much lower in patients with subtype C infection. In studies conducted in North America and Europe, individuals who developed the D30N mutation appeared more likely to respond to a second-line protease inhibitor than people with other patterns of protease resistance.
In the review carried out by the Public Health Laboratory’s virology reference group at Birmingham University, those with subtype C were found to be more likely to develop the L90M mutation associated with protease inhibitor cross resistance.
In people never treated with protease inhibitors and in those whose treatment was failing, minor mutations, which occur naturally and do not lead in themselves to drug resistance, were also seen to differ from those usually seen in sub-type B.
"There's little concordance between the mutations seen in subtypes B and C. We need to data on the susceptibility of subtype C mutations to protease inhibitors so we can establish the treatment implications" concluded Dr Cane.