Neumann AU, Mallet A, Calvez V, Li T, Tubiana R, Katlama C, Autran B; International Conference on AIDS.
Int Conf AIDS. 1998; 12: 12-3 (abstract no. 267/11153).
Bar-Ilan University, Life Sci. Dept., Ramat-Gan, Israel.
BACKGROUND: Although current highly active anti-Retroviral therapy (HAART) is very effective in controlling HIV replication, still in many patients viral load in plasma persists for long periods at levels above 20 HIV RNA copies/ml. The source for this virus level is not clear and a few possible explanations were suggested to explain it, each with different implications for treatment. Here, we test various such models using mathematical analysis of HIV and T-cells kinetic data. METHODS: 10 patients received triple therapy (indinavir/AZT/3TC) for a month. Treatment was then interrupted for a month, at which point the same treatment was again re-started. Plasma and cellular viral load were frequently measured, as well as CD4, CD8 and other T-cell markers. Kinetic data was fit with 3 different models: a) Infected cells with different life spans; b) Infected cells with different susceptibility to therapy; c) Infected cells in two compartments, one of which is a drug sanctuary. RESULTS: Once therapy started, viral load in plasma has undergone a multi-phasic decline with slowing decay rates: average t1/2 = 0.8 days (between days 1 and 3 of therapy), 1.5 (days 3-7), 8.2 (days 7-28), and 80 (days 28-84). All three models could be fitted to this pattern of viral decline with insignificant differences in fitting error. Once therapy was interrupted there was a delay of 4-7 days before HIV rebound started. During this period there was a significantly consistent increase in CD4 and CD8 T-cell counts, correlated with T-cell phenotype modifications. The one compartment models can not reproduce this data. Only the drug sanctuary model explains both the viral rebound delay and the correlated T-cell increase. CONCLUSION: Kinetics of HIV multi-phasic decay during HAART can be explained by all three models for HIV persistence. However, only the model that assumes a drug sanctuary compartment can explain the delay in viral rebound at therapy interruption and the relation between HIV and T-cell dynamics. The possible existence of a drug sanctuary compartment has important implications for the development of future therapy strategies.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Antiretroviral Therapy, Highly Active
- Drug Therapy, Combination
- HIV Infections
- HIV Seropositivity
- Humans
- Indinavir
- Lamivudine
- Viral Load
- Zidovudine
- drug therapy
- therapy
Other ID:
UI: 102226694
From Meeting Abstracts