HIV PHENOTYPE SWITCHING DURING ANTIRETROVIRAL THERAPY - EMERGENCE OF SAQUINAVIR-RESISTANT STRAINS WITH LESS CYTOPATHOGENICITY

Objectives: The aim of the study was to investigate changes in virolog ical characteristics of HIV strains isolated from 38 HIV-seropositive subjects during antiretroviral therapy. Design and methods: Patients w ith a CD4+ cell count less than or equal to 300 x 10(6)/l were treated with zidovudine (12 individuals) and saquinavir (10 individuals) alon e or in combination (16 individuals). CD4+ cell count, viral load, HIV biological phenotype and drug resistance were evaluated during the st udy period. Results: After 52 weeks, 28 subjects (74%) harboured drug- resistant strains. In patients with a syncytium-inducing (SI) strain, a decline of CD4+ cell count and an increase of viral load were observ ed aside from the emergence of drug resistance. Conversely, al the eme rgence of antiretroviral resistance, an immunological and virological deterioration was observed only in patients who had a non-syncytium-in ducing (NSI) strain. During the study, a phenotype switching of HIV is olates was detected in eight (21%) patients and a temporal corresponde nce between the appearance of phenotype switching and the emergence of drug resistance was found in seven cases. Th ree patients harbouring saquinavir-resistant strains showed a switch from SI to NSI variants a ssociated with a moderate increase in CD4+ cell count. Conclusions: Th e emergence of resistant strains during antiretroviral therapy may be associated with the selection of viral strains with less cytopathogeni city, while it could become a poor prognostic sign in patients with NS I isolates.