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 virological characteristics of HIV strains isolated from 38 HIV-seropositive subjects during antiretroviral therapy. Design and methods: Patients with a CD4+ cell count less than or equal to 300 x 10(6)/l were treated with zidovudine (12 individuals) and saquinavir (10 individuals) alone or in combination (16 individuals). CD4+ cell count, viral load, HIV biological phenotype and drug resistance were evaluated during the study 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 observed aside from the emergence of drug resistance. Conversely, al the emergence of antiretroviral resistance, an immunological and virological deterioration was observed only in patients who had a non-syncytium-inducing (NSI) strain. During the study, a phenotype switching of HIV isolates was detected in eight (21%) patients and a temporal correspondence 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 associated with a moderate increase in CD4+ cell count. Conclusions: The emergence of resistant strains during antiretroviral therapy may be associated with the selection of viral strains with less cytopathogenicity, while it could become a poor prognostic sign in patients with NSI isolates.