Structured treatment interruptions as a potential alternative therapeutic regimen for HIV-infected patients: a review of recent clinical data and future prospects.

Research Institute for Genetic and Human Therapy at IRCCS Policlinico S. Matteo, P. le Golgi, 2-27100 Pavia, Italy.
Journal of Antimicrobial Chemotherapy (Impact Factor: 5.44). 09/2002; 50(2):155-60.
Source: PubMed

ABSTRACT Highly active antiretroviral therapy (HAART) allows for substantial control of HIV replication in vivo, and has caused a significant decline in morbidity and mortality rates among patients. However, eradication of the virus from the body is not possible. Therefore, HAART necessarily becomes a life-long treatment and this is associated with several problems: (i) the high cost of therapy; (ii) increased frequency of drug-related side effects; (iii) viral resistance; and (iv) poor patient adherence to the treatment. Based on these considerations, among other alternative strategies, structured treatment interruptions (STI) have been proposed with the potential object-ive of inducing immune-mediated control of HIV replication in HIV-infected patients. The available clinical data indicate that STI might increase HIV-specific, cell-mediated immune responses in patients treated during primary HIV infection; however, it does not seem to have the same effect in patients treated during chronic infection. Nevertheless, in chronically infected patients STI might limit drug-related side effects by decreasing exposure to drugs, without influencing the efficacy of the therapy. In addition, recent data suggest a possible role for immune-modulations such as hydroxyurea and therapeutic vaccines as adjuvant therapies for limiting viral rebound in these patients. Preliminary indications suggest that there is reduced hope for STI as a salvage therapy. Finally, it is important to stress that no controlled, randomized studies of STI have been held in humans, and it is not possible to evaluate fully the clinical impact of such a strategy. Therefore, clinicians and patients should avoid using STI outside the setting of controlled clinical trials.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In der vorliegenden Arbeit werden die Verträglichkeit, Wirksamkeit und Lebensqualität einer Hydroxyurea (HU) enthaltenden antiretroviralen Kombinationstherapie evaluiert. Bei HIV-Patienten mit Therapieversagen konnte gezeigt werden, dass die Umstellung der Therapie auf eine HU enthaltende ART eine effektive und verträgliche Therapieoption darstellt. Die Viruslast konnte drastisch gesenkt werden, die Steigerung der CD4-Zellen wurde jedoch nicht in zufrieden stellender Höhe erreicht. Subjektiv wurde die Therapiekombination sehr gut vertragen.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several diseases involve complex interplay between an infection and the body’s defences. Concerning AIDS, for example, this corresponds to developments in the immune system’s responses and the HIV virus’ counter-responses. Treatment for such diseases involves, at specific times, delivery of an agent that inhibits the infection. We hypothesise that: given a credible model of the combined dynamics of infection and response, the timing and quantities involved in treatment can be valuably investigated using that model. In particular, we investigate searching for optimised treatment plans with an evolutionary algorithm (EA). Our test case is a cellular automaton (CA) model of HIV dynamics, extended to incorporate HAART therapy (a favoured HIV treatment).An EA is wrapped around this model, and searches for treatments that maximally delay onset of AIDS, given certain constraints. We find that significant improvements over default HAART strategy are readily discovered in this way.
    Parallel Problem Solving from Nature - PPSN IX, 9th International Conference, Reykjavik, Iceland, September 9-13, 2006, Procedings; 01/2006
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: HIV-1 eradication from infected individuals has not been achieved with the prolonged use of highly active antiretroviral therapy (HAART). The cellular reservoir for HIV-1 in resting memory CD4(+) T cells remains a major obstacle to viral elimination. The reservoir does not decay significantly over long periods of time but is able to release replication-competent HIV-1 upon cell activation. Residual ongoing viral replication may likely occur in many patients because low levels of virus can be detected in plasma by sensitive assays and transient episodes of viremia, or HIV-1 blips, are often observed in patients even with successful viral suppression for many years. Here we review our current knowledge of the factors contributing to viral persistence, the latent reservoir, and blips, and mathematical models developed to explore them and their relationships. We show how mathematical modeling has helped improve our understanding of HIV-1 dynamics in patients on HAART and of the quantitative events underlying HIV-1 latency, reservoir stability, low-level viremic persistence, and emergence of intermittent viral blips. We also discuss treatment implications related to these studies.
    Journal of Theoretical Biology 07/2009; 260(2):308-31. DOI:10.1016/j.jtbi.2009.06.011 · 2.30 Impact Factor