lam resistance in patients who never took antivirals so even entecavir is not totally safe

[stef2011]

http://archive.mail-list.com/hbv_research/message/20111218.203256.018c61a9.en.html

Author: [email protected]
Date: 2011-12-18 21:32 +100
To: hbv_research
Subject: Lamivudine resistance mutations in patients with genotype D
World J Gastroenterol. 2011 Dec 7;17(45):4987-92.
Lamivudine resistance mutations in patients infected with hepatitis B virus genotype D.
Source: http://www.ncbi.nlm.nih.gov/pubmed/22174548
Yildiz O, Aygen B, Demirtürk N, Demirdal T, Inan D, Yildirmak T, Kantürk A, Tütüncü E, Group HB.
SourceOrhan Yildiz, Bilgehan Aygen, Department of Infectious Diseases and Clinical Microbiology, Medical School of Erciyes University, 38039 Kayseri, Turkey.

Abstract
AIM: To determine the distribution of viral genotypes for primary or acquired lamivudine resistance.

METHODS: A total of 283 patients with chronic hepatitis B virus (HBV) infection (245 patients with chronic hepatitis B and 38 inactive hepatitis B surface antigen carriers) were included in the study. The HBV genotype was determined by using quantitative real-time polymerase chain reaction and sequence analysis, and tyrosine-methionine-aspartate-aspartate (YMDD) motif mutations were determined using the reverse transcriptase hybridization method.

RESULTS: Lamivudine resistance was determined in a total of 25 (10.7%) chronic hepatitis B patients. Eight subjects (4%) had primary resistance to lamivudine, and 17 (53.1%) had secondary resistance to lamivudine. Genotype D, which was isolated from 267 of the patients with chronic HBV infection, was the dominant genotype in Turkey.

CONCLUSION: Identification of YMDD motif mutations should have a positive impact on the selection of proper antiviral medication for patients, even for those who are nucleoside naïve.

[stef2011]

yes of course, and it is not so rare since my mutant q215s and q215q has cross resistance already with lam and adv and i never took these.this was at high population >20%

usually with this mutation there are others at less than 20% population, the test taken in 2010 couldn t show, lam mutants could be there

lately also hbsag mutants, also present naturally, can be important for etv response too, few research centers are checking this

[4est]

so what you say is that, it is possible to develop NUC resistance without taking NUCs and this resistance can be discovered using deep sequence and after that the treatment should be start accordingly.

[stef2011]

acquired resistance is similar with secondary resistance ?

i dont understand the question

hbv exisits as quasispieces that are made by replication error.
both primary, secondary mutations are due to this replication error which is the same without or during therapy.
the quasispieces/mutations/resistance just develops slower as the replication is lower

[4est]

I'm not a buddy-builder I only have a bigger constitution :) and i read about the BMI and find out that exist more then one way to measure this, but i will look over the way to measure the fat in the body.

anyway, back on the original question, acquired resistance is similar with secondary resistance ?

[stef2011]

in case of bodybuilders you should divide muscles mass from fat mass, it is the fat mass to make problems

i ve read it is very difficult to measure this accurately, i think there are a few machines to do it

[4est]

interesting remark about BMI level - seams to me that I have to loss some kilo, even if I'm not consider myself a fat person (also no other person consider me a fat person, only a big/athletic one)

[stef2011]

the big problem is that ultra deep sequence is finding most mutations already present baseline, anyway even these normal tests found mutants present already in about 10%

primary mutations are those directly making drug useless

secondary mutations are those that henance replication capacity of primary mutations so that hbv repication gets back to wild type levels

secondary mutations are very dangerous because they are cross resistant to many/all the drugs so that they make useless all other drugs too

locarnini had very good posters about this:
http://www.ihlpress.com/pdf%20files/resistance06_presentation/A_Thurs_Locarnini_sec.pdf

it is also strange but higher bmi than 24,9 has also higher resistance rates.i think immune system of patient with high bmi are weaker and so more mutants can develop

[4est]

what is the difference between primary and acquired lamivudine resistance ?

acquired lamivudine resistance is not referring to the one that had LAM treatment and develop resistance?

[stef2011]

no they just checked the mutants on patients with no therapy, but having first or secondary mutants before therapy is failure on lam, possibly on adv if q215s is present and etv too

[grmr]

that's definetly confirm TFV is safer on resistance... isnt it? cannot open the link.. how long did they stay on ETV?