An international collaboration which aims to monitor the transmission of drug resistant HIV has found that a significant number of HIV-positive Europeans carry resistant virus, even before they have taken HIV treatment. Researchers involved in the CATCH study, which reported data at last week’s International AIDS Society Conference in Paris, say the results support the gathering of resistance data in everyone who is newly-infected with HIV.
CATCH was established to determine the prevalence of drug resistance in treatment naïve Europeans during the period from 1996 to 2002. Data presented in Paris involve 1,633 participants recruited from sixteen European countries and from Israel. Data gathered from France and the UK were not included. Seventy-two per cent of the group were male, and 69% were infected with HIV subtype B, the subtype most common in Europe and the USA.
Blood samples were genotyped using the Retrogram test, and mutations were classified according to published guidance on antiretroviral resistance from the International AIDS Society USA Panel. Overall, primary resistance mutations were detected in 9.6% of the cohort. By drug class, mutations associated with resistance to NRTIs were seen in 6.9%; to NNRTIs in 2.6%; and to PIs in 2.2%. Genotypic resistance to two or more classes was noted in 1.7%.
An approximate date of infection was available for an undisclosed majority of the study group, allowing comparisons to be made between those whose infection was very recent (acute infection) and those who had been HIV-positive for longer (chronic infection). The prevalence of primary resistance mutations in people infected for less than one year was not significantly different to that observed in people infected for longer, suggesting transmitted resistance persists.
Resistance mutations were more common in people infected with subtype B than with a non B subtype (11.3% versus 3.3%). This is to be expected given the longer history of exposure to HIV treatments in the industrialised West than in those regions where non B subtypes are predominant.
Reduced susceptibility to specific drugs
Primary resistance mutations were detected in 157 CATCH participants. Interpretation of these 157 genotypes forecast reduced NRTI susceptibility in 17% for 3TC, and in close to the 40% mark for AZT and d4T. Twenty-six per cent were predicted to harbour reduced NNRTI susceptibility, and between 10% and 22% reduced susceptibility to PIs, depending on the drug.
The study did not set out to evaluate responses to treatment, and so these predictions were not tested. Nevertheless, these data will be warmly embraced by those who propose a role for resistance testing in the initial selection of HIV therapy, an issue on which there continues to be little consensus within the international HIV community. A recent revision of the British HIV Association Treatment Guidelines, available in draft form here at aidsmap.com, offers this: "Resistance testing prior to therapy may be of crucial value for a proportion of patients who carry resistance mutations, especially in the context of demonstrable transmitted resistance. It is recommended using the nearest available sample to seroconversion or presentation."
van der Vijver DAMC et al. Analysis of more than 1600 newly diagnosed patients with HIV from 17 European countries shows that 10% of the patients carry primary drug resistance: The CATCH study. 2nd International AIDS Society Conference, Paris 13-16 July, LB1, 2003.