Article

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: 5.34). 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.

0 Bookmarks
 · 
30 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: One of the consequences of viral quasispecies dynamics is the presence, in the mutant spectrum, of minority memory genomes that reflect those variants that were dominant at an earlier phase of the same evolutionary lineage. Replicative and cellular (or anatomical) contributions to quasispecies memory were previously defined during intrahost evolution of human immunodeficiency virus type 1 (HIV-1) [Briones, C., Domingo, E., Molina-París, C., 2003. Memory in retroviral quasispecies: experimental evidence and theoretical model for human immunodeficiency virus. J. Mol. Biol. 331, 213-229.]. However, the effects of replicative memory regarding virus evolution in vivo have not been investigated. Here we document that a multidrug-resistant (MDR) HIV-1, present at memory level, determined the ensuing evolution of the virus in an infected patient. Nucleotide sequencing and detailed phylogenetic analyses of sequential viral populations and individual molecular clones evidenced that the progeny of a minority MDR genome during a treatment interruption contributed the dominant genomes when an antiretroviral treatment was restored. An extension of a mathematical model of establishment and maintenance of memory, based on quasispecies theory, supports the experimental data. Therefore a replicative memory subpopulation, not detectable in a consensus nucleotide sequence, affected decisively subsequent states of viral evolution in vivo.
    Gene 01/2007; 384:129-38. · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Antiretroviral (ARV) drugs account for >70% of the direct costs of HIV care. Changing practices in the use of ARV drugs may have major cost implications for the care budget within a regional population. Objective: To characterize and quantify the precise changes in the use of ARV within an entire HIV-infected population and to develop an approach to monitor the cost impact of future changes on the ARV budget. Design, Setting, and Participants: Socio-demographic, clinical, and primary-costing data were obtained from all 1218 HIV-positive patients receiving HIV care and living within southern Alberta, Canada between 1995 and 2003. Main Outcome Measures: Mean per patient per month (PPPM) costs in $Can (2003 values) were used for the basis of comparison. Actual and predicted changes in costs are presented as percentage changes. Results: After increasing 226% between 1996 and 1998, total PPPM ARV costs climbed only 6.7% from 1998 and 2003. Four counterbalancing forces contributed to this relative stabilization in costs: (i) the increased use of four or more ARV drugs to treat resistant HIV; (ii) the use of newer, more expensive ARV drugs (both [i] and [ii] increased total ARV costs by 22%); (iii) a delay in initiating ARV therapy to a lower CD4 count threshold; and (iv) the increased use of treatment interruptions (both [iii] and [iv] decreased total ARV costs by 15.3%). Increased or decreased use of these practices differentially affected mean ARV costs by 5-25% or more. Conclusions: Changing medical practices in terms of ARV use may have a major impact on the ARV budget. Detailed knowledge of both the entire HIV population being served, along with comprehensive information on current and planned changes in ARV use are essential for projecting both immediate and longer term funding.
    Disease Management and Health Outcomes 01/2005; 13(3):209-217. · 0.36 Impact Factor
  • 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.

Full-text

View
0 Downloads