RESISTANCE, REMISSION, AND QUALITATIVE DIFFERENCES IN HIV CHEMOTHERAPY

To understand the role of qualitative differences in multidrug chemoth erapy for human immunodeficiency virus (HIV) infection in virus remiss ion and drug resistance, we designed a mathematical system that models HIV multidrug chemotherapy including uninfected CD4+ T cells, infecte d CD4+ T cells, and virus populations. The model, which includes the l atent and progressive stages of the disease and introduces chemotherap y, is a system of differential equations describing the interaction of two distinct classes of HIV (drug-sensitive [wild type] and drug-resi stant [mutant]) with lymphocytes in the peripheral blood; the external lymphoid system contributes to the viral load. The simulations indica te that to preclude resistance, antiviral drugs must be strong enough and act fast enough to drive the viral population below a threshold le vel. The threshold depends upon the capacity of the virus to mutate to strains resistant to the drugs. Above the threshold, mutant strains r apidly replace wild-type strains. Below the threshold, resistant strai ns do not become established, and remission occurs. An important disti nction between resistance and remission is the reduction of viral prod uction in the external lymphoid system. Also the virus population rapi dly rebounds when treatment is stopped even after extended periods of remission.