[Decrease of HIV-1 replicative capacity after serial passage in MT-4 cells under conditions of the combined...

The replicative activity of HIV-1/IIIB was determined in MT-4 cells under conditions of combined HIV reverse transcriptase and protease inhibitors in the presence of four different drug cocktails: (1) phosphazide, didanosine, nevirapine; (2) stavudine, didanosine, nevirapine; (3) phosphazide, didanosine, nevirapine, indinavir; (4) stavudine, didanosine, nevirapine, indinavir. The concentration of every inhibitor was 10 times higher than the 50% effective concentration. Alpha interferon was used as a natural antiretroviral agent in addition. The virus was subjected to 5 serial passages in the presence of the drug cocktails and then to 5 serial passages without the agents using cocultivation of infected and uninfected cells at ratio 1:5 to increase virus activity. Virus replication in the presence of all the drug combinations resulted in the appearance of HIV-1 variants with low replicative activity that was insignificantly increased during further passages even without the antiretroviral agents. If extrapolated to the clinical practice, these results indicate that all the drug cocktails were effective inhibitors of HIV-1 replication because the virus variants with high replicative activity did not emerge. Moreover, the results showed that the clinical use of the drug cocktails was promising.