Rate of YMDD motif mutants in lamivudine-untreated Iranian patients with chronic hepatitis B virus infection

Abstract

Although the natural occurrence of YMDD motif mutants in lamivudine-untreated patients with chronic hepatitis B has been reported, these mutants were not detected in Iranian lamivudine-untreated chronic hepatitis B patients.

Drug-Related Mutational Patterns in Hepatitis B Virus (HBV) Reverse Transcriptase Proteins From Iranian Treatment-Naïve Chronic HBV Patients

“…The rtA181T change has been reported to occur in the absence of rtM204I/V and is considered a primary resistance mutation (19, 20). In this study we found that L180M 3.37% (11), M204I 2.76% (9), and M204V 1.23% (4) were more common than had been reported previously in Iran (21, 22). Our results fall between the extremes reported by other studies around the world (7-12, 23).…”

“…Compared to the lamivudine, resistance to ADV usually occurs less frequently and takes longer to emerge. Adefovir-resistant HBV mutations have not been detected in patients up to 48 weeks into therapy and increase to 3%, 11%, 18%, and 29% following 2, 3, 4, and 5 years of therapy, respectively (22, 24). HBV genotype D is associated with an increased risk of adefovir resistance (11, 25).…”

“…The latter finding had a mutation frequency of 1.64% and was higher than the other domains studied (Figure 1). These mutations may be regarded as secondary resistance mutations, as they have been associated only with very low-level resistance in vitro (22, 26). These secondary mutations have also been detected in the absence of rtN236T (both alone and in combination) in patients who have either not responded to or have had a virological breakthrough during adefovir treatment (32-34).…”

The incidence of Drug- Resistant Mutants in Patients with Chronic HBV Infection After Lamivudine Treatment

“…An investigation in Iranian population showed that patients without Lamivudine therapy had no rtL80M / M204V mutations (24). Also, another study on infected blood donors with HBV showed that Lamivudine resistance mutations (rtL180M / rtM204V) strains are not detected in Iranian blood donors (10).…”

Naturally occurring hepatitis B virus reverse transcriptase mutations related to potential antiviral drug resistance and liver disease progression

“…These include 32 articles published from institutions based in Asia (12 published from China, four from Iran, four from Turkey, four from India, three from Japan, two from Taiwan, and one each from Korea, Jordan, and Indonesia), 11 articles published from institutions based in Europe (six from Italy, two from Germany, and one each from Austria, Ireland, and Spain), four articles published from institutions based in North America (three from United States and one from Canada), two articles published from institutions based in South America (both from Brazil), and one article published from an institution in South Africa (Supplementary Table 1 ). Among the 50 studies, 36[ 12 , 20 , 21 , 32 - 58 , 60 - 65 ] used direct PCR sequencing methods, 11[ 22 - 28 , 59 , 66 - 68 ] used the INNO-LiPA line assay, and 3[ 29 - 31 ] detected RT mutations by ultra-deep pyrosequencing (UDPS). Seventeen articles[ 21 , 26 , 27 , 30 , 31 , 34 , 35 , 37 - 39 , 42 , 43 , 46 - 48 , 53 , 58 ] included treatment-naïve patients infected with genotypes B and C, one study[ 32 ] with genotypes A and D, eleven studies[ 22 , 28 , 29 , 36 , 50 , 51 , 55 , 56 , 60 , 63 , 68 ] with genotype D, one study[ 33 ] with genotype C, and fifteen studies[ 20 , 23 - 25 , 40 , 41 , 44 , 45 , 52 , 54 , 57 , 61 , 64 , 65 , 67 ] with more than three genotypes ( e.g ., A, ...…”