Comput Methods Programs Biomed - Computer simulation of structured treatment interruption for HIV infection.


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The use of highly active antiretroviral therapy (HAART) for suppression of measurable levels of virus in the body has greatly contributed to restoration and preservation of the immune system in HIV positive patients. However, short and long term problems associated with HAART have led to proposals for alternative treatment strategies for controlling HIV infection. In particular, structured treatment interruptions (STIs) that consist of therapy withdrawal and re-initiation according to specific criteria have been considered. The aim of these STIs was one or both of: (i) to stimulate the immune system to react to HIV, (ii) to allow re-emergence of wild-type virus and thereby reduce problems of drug resistance. However, a number of clinical trials of STIs have shown adverse outcomes for patients under discontinuous therapy, including serious health risks associated with treatment interruptions. In this paper we consider in some detail two of the larger clinical studies, namely, (a) strategies for management of anti-retroviral therapy (SMART); (b) Staccato study. For each of these studies we perform computer simulations of the treatment strategies. These simulations suggest several underlying reasons for the adverse outcomes during treatment interruption. In particular, HIV infection exhibits rapid dynamic load changes, and therefore measurement based treatment regimes need to be carefully designed to avoid large transients in healthy CD4+ T cell count. Furthermore, repeated treatment interruptions may accelerate the emergence of resistant mutant virus and may increase the infection of long term reservoirs such as macrophages which will accelerate progression to AIDS.

Resumo Limpo

use high activ antiretrovir therapi haart suppress measur level virus bodi great contribut restor preserv immun system hiv posit patient howev short long term problem associ haart led propos altern treatment strategi control hiv infect particular structur treatment interrupt stis consist therapi withdraw reiniti accord specif criteria consid aim stis one stimul immun system react hiv ii allow reemerg wildtyp virus therebi reduc problem drug resist howev number clinic trial stis shown advers outcom patient discontinu therapi includ serious health risk associ treatment interrupt paper consid detail two larger clinic studi name strategi manag antiretrovir therapi smart b staccato studi studi perform comput simul treatment strategi simul suggest sever under reason advers outcom treatment interrupt particular hiv infect exhibit rapid dynam load chang therefor measur base treatment regim need care design avoid larg transient healthi cd t cell count furthermor repeat treatment interrupt may acceler emerg resist mutant virus may increas infect long term reservoir macrophag will acceler progress aid

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