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. 1999 Dec 7;96(25):14464–14469. doi: 10.1073/pnas.96.25.14464

Figure 4.

Figure 4

Modifications of the basic treatment window regime resulting in the re-establishment of CTL memory during the asymptomatic period of the infection. Again, only memory CTL responses generated in the presence of CD4 cell help are considered. Because we assume that CD4 cell help is significantly impaired, these CTL are at low levels before start of therapy. Shading indicates drug therapy. (i) Multiple drug windows. In low immune responders and in patients with advanced HIV disease, the basic drug window treatment regime may result only in partial establishment of CTL memory and failure to control the virus. Further phases of drug therapy separated by treatment windows may successively boost the CTL response, resulting in the eventual generation of efficient CTL memory and long-term control of HIV. Parameters were chosen as follows: λ = 1; d = 0.1; β = 0.5; a = 0.2; p = 1; c = 0.027; b = 0.001; q = 0.5; h = 0.1; s = 0.0042. (ii) Drug therapy in conjunction with vaccination with persisting antigen. Although virus load is kept at low levels because of antiviral therapy, the patient is vaccinated with a mixture of immunogenic HIV peptides. This boost induces the establishment of CTL memory whereas drug treatment keeps HIV-induced immune impairment to a minimum. During the generation of CTL memory, HIV load sharply drops to very low levels, because the CTL response is boosted in the absence of HIV replication, allowing the rising CTL to reduce virus load to ever decreasing values. This process theoretically could clear the infection. However, the presence of latently infected cells and reservoirs inaccessible to CTL renders this goal difficult to achieve. Thus, when drug treatment is stopped, virus load is likely to transiently increase before being controlled in the long term by CTL memory. Vaccination with a recombinant virus vector expressing HIV-specific proteins was modeled according to the basic virus infection model (38). Denoting uninfected target cells for the vector as x2, and vector-infected cells by y2, the model is given by ẋ2 = λ2− d2x2 − β2x2y2; ẏ2 = β2x2y2 − a2y2 − p2y2z. The CTL response is equally stimulated both by HIV and the vaccine. Parameters were chosen as follows: λ = 1; d = 0.1; β = 0.5; a = 0.2; p = 1; c = 0.1; b = 0.001; q = 0.5; h = 0.1; s = 0.0042; λ2 = 1; d2 = 0.1; β2 = 0.5; a2 = 0.2.