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Conference
"First Line Therapy: A Virological Perspective" Anna Maria Geretti (biography) English - 2005-06-06 - 60 minutes
(45 slides)
Summary : Factors such as adherence, toxicity, drug interactions, cost and resistance pathways are important to consider when choosing a first line therapy. In the case of double nucleoside backbone regimens, the standard and therefore largest set of data available is for the co-formulated ZVD/3TC regimen. However, ZVD/3TC seems to be inferior to ABC/3TC and TDF/3TC in terms of potency and toxicity. Of these 3 co-formulations, ABC/3TC appears to be the most promising combination with the exception of the acute hypersensitivity reactions associated with ABC (AHS).
As ABC dosage was shown to have a limited effect on the extent of the AHS, Dr Geretti reviews previous studies aimed to identify genetic factors that can predict the occurrence of AHS. She reviews studies by Mallal et al (2002), Hetherington et al. (2002) and Martin et al. (2002), who have screened for markers such as HLA-B*5701 and Hsp70hom’C’ to determine their predictive ability of AHS. However, in a diverse multiethnic population, screening for these genetic markers is not only lengthy but may also be inaccurate.
The question that Dr. Geretti brings to our attention is the importance of DNA screening for resistance mutations in ethnically diverse groups to determine the ideal first line antiretroviral therapy. Dr. Geretti examines in detail the genotypic baseline resistance and resistance at failure in several drug combinations.
Learning objectives : After viewing this presentation, participants will be able to discuss:
- Comparison of co-formulated double nucleoside backbone regimens;
- Abacavir hypersensitivity reaction (AHS);
- Genetic markers associated with AHS;
- Baseline resistance mutations;
- Resistance mutations associated with specific drug combinations.
Bibliographic references : Phillips, Elizabeth J a; Wong, Gavin A b; Kaul, Rupert c; Shahabi, Kamnoosh c; Nolan, David A e; Knowles, Sandra R d; Martin, Annalise M e; Mallal, Simon A e; Shear, Neil H dClinical and immunogenetic correlates of abacavir hypersensitivity.AIDS. 19(9):979-981, June 10, 2005.
Seth Hetherington, Arlene R Hughes, Michael Mosteller, Denise Shortino, Katherine L Baker, William Spreen, Eric Lai, Kirstie Davies, Abigail Handley, David J Dow et al.Genetic variations in HLA-B region and hypersensitivity reactions to abacavir The Lancet, Volume 359, Issue 9312, 30 March 2002, Pages 1121-1122
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