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Conference
"Treatment Interruptions in HIV Infection" Carlos Zala (biography) English - 2003-03-29 - 31 minutes
Summary : Treatment interruptions are used in acute infection, chronic infection and salvage therapy. In acute infection it is used to enhance immune control of viral replication and in salvage therapy to re-populate with WT virus. Here we will focus on treatment interruption in chronic infection, which is done to limit toxicity and cost. The goal of STI in chronic infection is to reduce therapeutic burden in terms of toxicity, QOL, spread of resistant HIV, and cost, without promoting resistance, reducing treatment options or promoting spread of HIV. A problem with STI in this case is that it may select for resistant mutants, and also in the viral rebound phase the patient becomes an efficient transmitter of HIV infection. As indicated by the results of the Staccato Trial, where the one week on – one week off arm of the study was closed due to high rates of virologic failure, we can deduce that it’s probably not possible to maintain an undetectable viral load and a CD4 response with intermittent therapy. An alternative approach would be to allow viral load rebound, while focusing on viral load set point. The goal would be to reduce overall drug exposure while maintaining protection against clinical progression. The Swiss Spanish Intermittent Therapy Trial (SSIT) showed this approach to be effective in about 20% of patients. Another, more convenient approach would be to ignore the viral load rebound and focus on CD4 maintenance. This was tested in the trial designed by Dr Vella, which was presented at the 10th CROI meeting, where the CD4 counts correlated nicely with the viral load but had problems with accumulation of resistant mutations in all 3 drug classes. The BC Centre for Excellence data also shows that the probability of remaining on STI decreases over time. So STI remains an attractive hypothesis, but more research is needed and until then it may be a valuable tool in selected clinical settings.
Learning objectives : The participant will gain an understanding of the status of STI use in chronic HIV infection, in terms of potential benefits and current problems.
- The goal of STI in chronic infection is to reduce therapeutic burden in terms of toxicity, QOL, spread of resistant HIV, and cost, without promoting resistance, reducing treatment options or promoting spread of HIV.
- Problems with STI in this case are the selection of resistant mutants and the efficacy of transmission at times of viral load rebound.
- The Swiss Spanish Intermittent Therapy Trial (SSIT) tested STI focusing on viral load set point, where it was successful in about 20% of patients.
- STI focusing on CD4 maintenance showed long term success, but increased selection of mutations in all 3 drug classes (Vella S, 10th CROI).
- The BC Centre for Excellence data shows that the probability of remaining on STI treatment decreases over time.
- STI is still an attractive hypothesis but needs more research and may be useful in selected clinical settings.
Bibliographic references : http://jvi.asm.org/cgi/content/full/76/14/7000?view=full&pmid=12072500
J Virol 2002 Jul;76(14):7000-9
Origin of human immunodeficiency virus type 1 quasispecies emerging after antiretroviral treatment interruption in patients with therapeutic failure.
Kijak GH, Simon V, Balfe P, Vanderhoeven J, Pampuro SE, Zala C, Ochoa C, Cahn P, Markowitz M, Salomon H
http://jvi.asm.org/cgi/content/abstract/77/5/3229
J Virol 2003 Mar;77(5):3229-37
Genetic characterization of rebounding human immunodeficiency virus type 1 in plasma during multiple interruptions of highly active antiretroviral therapy.
Dybul M, Daucher M, Jensen MA, Hallahan CW, Chun TW, Belson M, Hidalgo B, Nickle DC, Yoder C, Metcalf JA, Davey RT, Ehler L, Kress-Rock D, Nies-Kraske E, Liu S, Mullins JI, Fauci AS
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