Presence of genotypic resistance in nucleoside analogue-treated HIV-1-infected patients with undetectable viral load

Patients harbouring drug-resistant viruses usually suffer a rise in serum v iraemia after a variable period of time. We have investigated the relations hip between the appearance of resistant genotypes and the viral load of eac h patient after treatment, Our objective was to assess the association betw een human immunodeficiency virus (HIV) RNA plasma levels and the number of drug resistance-associated point mutations after treatment. A total of 150 patients from three reference centres in Spain (Madrid, Barcelona and Sevil le) from a previous study (Erase Study) were included. Patients had at that time undergone antiretroviral treatment with nucleoside analogues for at l east 1 year (zidovudine/didanosine; zidovudine/zalcitabine; zidovudine/zalc itabine/lamivudine; zidovudine/didanosine/lamivudine). In this study, plasm a viraemia in these patients was quantified and a line probe assay was used to determine the genotype of the virus. Viral load was significantly highe r in patients harbouring virus with more than three mutations than in those individuals who harboured wild-type strains (P<0.05). Surprisingly, when p atients with viral load <500 copies/mt (13/150) were analysed, only two car ried wildtype strains, whereas three had virus with more than three point m utations. The viral load of six samples was assayed using an ultrasensitive test (detection limit <20 copies/ml). Of the three samples where viral loa d was <20 copies/ml, one patient harboured wild-type virus, whereas two car ried mutant virus strains. These results suggest that even in patients with undetectable viral loads by conventional methods, viral replication may co ntinue and mutations develop. Therefore, standard values of plasma viraemia for measuring the effectiveness of the treatment should be reconsidered wh en patients are on antiviral regimens of just two or three nucleoside analo gues.