Genotypic resistance to lamivudine among hepatitis B virus isolates in Mexico.
BACKGROUND
Drug resistance of hepatitis B virus (HBV) is an increasing clinical problem. Resistance to lamivudine in HBV isolates in Mexico has been poorly explored.


OBJECTIVE
To characterize the mutation patterns associated with genotypic resistance to lamivudine and their prevalence among HBV isolates in Mexico.


METHODS
Thirty-nine Mexican HBV isolates were analysed by PCR and line probe assay for detection of genetic variants in the polymerase open reading frame domains B and C (INNO-LiPA HBV DR; INNOGENETICS N. V., Ghent, Belgium). This assay detects wild-type and mutations at codons 180, 204 and 207 of the HBV polymerase gene, and at codon positions 171, 172, 195, 196, 198 and 199 of the HBV surface antigen (HBsAg). HBV isolates were obtained from HBsAg-positive serum samples of 15 chronic hepatitis patients, two haemodialysis patients with chronic HBV carriage, 20 men found positive for HBsAg when seeking HIV testing and two AIDS patients with chronic HBV infection. None of the participants had received antiviral therapy.


RESULTS
Overall, HBV wild-type was found in 37 (94.9%) out of the 39 isolates studied. Two (5.1%) out of the 39 isolates showed mixed wild-type and mutant populations. These mutations occurred in isolates from one hepatitis patient and one haemodialysis patient. The isolate from the hepatitis patient showed a double mutation at codon positions 180 (L180M) and 204 (M204V), thus a 2.6% prevalence of genotypic resistance to lamivudine was found. The isolate from the haemodialysis patient showed a single mutation at codon position 180 (L180M). The two HBV mutant isolates were further analysed for genotype and both isolates were genotype H.


CONCLUSIONS
HBV genotypic resistance to lamivudine exists in Mexican isolates. The results highlight the importance of testing for HBV resistance before treatment and have implications for a more rational use of drugs.
Alvarado-Esquivel
Cosme
C
Faculty of Medicine, Universidad Juárez del Estado de Durango, Durango, Dgo, and National Institute of Public Health, Morelos, Mexico. alvaradocosme@yahoo.com
de la Ascensión Carrera-Gracia
Manuela
M
Conde-González
Carlos Jesús
CJ
Juárez-Figueroa
Luis
L
Ruiz-Maya
Lilia
L
Aguilar-Benavides
Sergio
S
Torres-Valenzuela
Alejandro
A
Sablon
Erwin
E
D003062:Codon / Q000235:genetics; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005784:Gene Amplification; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008800:Mexico / Q000453:epidemiology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
D003062:Codon; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine