Human immunodeficiency virus drug therapy and virus

Analysis of the short-term dynamics of human immunodeficiency virus (HIV) type 1 infection in response to drug therapy has elucidated crucial kinetic properties of viral dynamics in vivo (D. D. Ho et al., Nature 373:123–126, 1995; A. S. Perelson et al., Science 271:1582–1586, 1996; X. Wei et al., Nature 373:117–122, 1995). Here we investigated long-term changes in virus load in patients treated with a combination of lamivudine and zidovudine to identify principal factors responsible for the observed 10- to 100-fold sustained suppression of virus load in vivo. Interestingly, most standard accounts of virus dynamics cannot explain a large sustained reduction without shifting the virus very close to extinction. The effect can be explained by taking into consideration either (i) the immune response against HIV, (ii) the killing of uninfected CD4 cells, or (iii) the differential efficacies of the drugs in different cell populations. Long-term treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients with a combination of lamivudine and zidovudine results in a 10- to 100-fold reduction of virus load and a 25 % increase in CD4 cell count, which is usually sustained for at least 1 year (5) (Fig. 1). Patients receiving this therapy show a rapid decline in virus load over several order