segunda-feira, novembro 20, 2006
Resistência diminui em Portugal?
Is HIV drug resistance in decline in Europe?
Three studies from Europe presented to the Eighth Glasgow International Congress on Drug Therapy in HIV Infection suggest that HIV drug resistance, especially to several drug classes, is in decline, largely due to improved treatment efficacy.
However researchers and activists have drawn different conclusions about what this means for the future of drug development.
Jurgen Vercauteren of the Rega Institute at Leuven in Belgium analysed all 3093 HIV isolates from drug experienced patients that were included in the Portuguese Resistance Database between July 2001 and March 2006. These 3093 samples of HIV came from 2373 patients.
Vercauteren defined HIV with ‘multi-drug resistance’ (MDR) as virus whose genotype indicated susceptibility to no more than one HIV antiretroviral, with the exceptions of enfuvurtide (T-20), tipranavir and darunavir.
An approximately equal number of viral isolates was sent to the Database each year, but during the study period the proportion that were multi-drug-resistant declined from 5.7 per cent in 2001-2 (33 out of 576 isolates) to 2.1 per cent in 2005-6 (13 out of 490 isolates). The decline was steady, with an average 20% decrease per year, and highly statistically significant (p=0.003).
The two factors associated with having MDR virus were length of treatment (16% increase in likelihood per year on treatment) and having an uncertain date as to the start of therapy, which increased the chance of having MDR-virus nearly eightfold. This was taken as Vercauteren as being a ‘surrogate marker’ for having had early and suboptimal ARV treatment.
Vercauteren said that though his findings only showed that the incidence of MCR HIV had declined in one country – Portugal – he expected it to be replicated throughout Europe, telling conference delegates “it is up to you to show us that”.
He said that his findings reflected the increasing efficacy of HAART and said that in the future new HIV drugs’ ability to tackle MDR HIV might become less important compared with ease of use, tolerability and lack of toxicity.
Vercauteren’s findings were questioned by some treatment activists. It is unlikely that in a country with the highest HIV prevalence in western Europe only 3093 resistance tests have been performed since 2001 and the Database may not reflect reality. It is also important to note that the incidence of drug resistance is much easier to measure than its prevalence; resistance will remain archived in patients on successful HAART and may give trouble in the future, but will not show up as currently active resistance.
It is also the case that some of the drugs now increasingly used as first-line therapy, such as the boosted protease inhibitors, are chosen precisely because of a high resistance threshold and were initially designed as salvage therapies. This is still clearly a desirable attribute of any new therapy.