Optimal timing and duration of induction therapy for HIV-1 infection.
The tradeoff between the need to suppress drug-resistant viruses and the problem of treatment toxicity has led to the development of various drug-sparing HIV-1 treatment strategies. Here we use a stochastic simulation model for viral dynamics to investigate how the timing and duration of the induction phase of induction-maintenance therapies might be optimized. Our model suggests that under a variety of biologically plausible conditions, 6-10 mo of induction therapy are needed to achieve durable suppression and maximize the probability of eradicating viruses resistant to the maintenance regimen. For induction regimens of more limited duration, a delayed-induction or -intensification period initiated sometime after the start of maintenance therapy appears to be optimal. The optimal delay length depends on the fitness of resistant viruses and the rate at which target-cell populations recover after therapy is initiated. These observations have implications for both the timing and the kinds of drugs selected for induction-maintenance and therapy-intensification strategies.
Curlin
Marcel E
ME
Department of Medicine, University of Washington, Seattle, Washington, USA.
Iyer
Shyamala
S
Mittler
John E
JE
D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods / Q000706:statistics & numerical data; D003198:Computer Simulation; D003661:Decision Support Techniques; D018450:Disease Progression; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000187:drug effects; D004359:Drug Therapy, Combination; D004360:Drug Therapy, Computer-Assisted / Q000379:methods / Q000706:statistics & numerical data; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000472:pathogenicity; D006207:Half-Life; D006801:Humans; D016015:Logistic Models; D009154:Mutation; D010347:Patient Care Planning / Q000592:standards; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents