{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:35:57Z","timestamp":1774647357346,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSP2023R350"],"award-info":[{"award-number":["RSP2023R350"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Several nucleotide analogues have been approved for use in treating hepatitis B virus (HBV) infection. Long-term exposure to therapy leads to the emergence of mutations within the HBV DNA polymerase gene, resulting in drug resistance, a major factor contributing to therapy failure. Chronic HBV patients from the Khyber Pakhtunkhwa province, Pakistan, who had completed 6 months of therapy participated in this study. Samples were collected from 60 patients. In this study, the entire reverse transcriptase domain of the HBV polymerase gene was amplified using nested polymerase chain reaction and sequenced. Drug-resistant mutations were detected in nine (22.5%) patients. All of these patients had lamivudine-resistant mutations (rtM204V + L180M), while seven individuals (17.5%) had both lamivudine- plus entecavir-resistant mutations (L180M + M204V + S202G). N236T, a mutation that gives rise to tenofovir and adefovir resistance, was observed in two (5%) patients. T184A, a partial drug-resistant mutation to entecavir, was found in five (12.5%) patients. Furthermore, other genotypic variants (100%) and vaccine escape mutations (5%) were additionally observed. Moreover, pN459Y (35%), pN131D (20%), pL231S (20%), pP130Q (17.5%), pS189Q (12.5%), pP161S (5%), pH160P (2.5%), pT322S (2.5%), and pA223S (2.5%) mutations in the polymerase gene, as well as sA166V (17.5%), sQ181K (12.5%), sV184R (7.5%), sA17E (5%), sP153S\/K (5%), sW156C (5%), sC76Y (2.5%), and S132F (2.5%) mutations in the small surface gene, were identified for the first time in this study. Phylogenetic analysis showed that genotype D was predominant amongst the HBV carriers. Subtype D1 was found in most patients, while two patients were subtype D9. These novel findings may contribute to the body of knowledge and have clinical significance for treating and curing HBV infections in Pakistan.<\/jats:p>","DOI":"10.3390\/microorganisms11112622","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T06:29:01Z","timestamp":1698128941000},"page":"2622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Phylogenetic Analysis and Emerging Drug Resistance against Different Nucleoside Analogues in Hepatitis B Virus Positive Patients"],"prefix":"10.3390","volume":"11","author":[{"given":"Maryam","family":"Gohar","sequence":"first","affiliation":[{"name":"Center of Biotechnology and Microbiology, University of Peshawar, Peshawar 25000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irshad Ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Center of Biotechnology and Microbiology, University of Peshawar, Peshawar 25000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amin","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Health & Biological Sciences, Abasyn University Peshawar, Peshawar 25000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Ajmal","family":"Khan","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Humaira","family":"Yasmin","sequence":"additional","affiliation":[{"name":"Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad 45550, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamshaid","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Center of Biotechnology and Microbiology, University of Peshawar, Peshawar 25000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3631-3354","authenticated-orcid":false,"given":"Sadia","family":"Butt","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Shaheed Benazir Bhutto Women University Peshawar, Peshawar 25000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajaz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1002\/jmv.24853","article-title":"Mutations associated with drug resistance and prevalence of vaccine escape mutations in patients with chronic hepatitis B infection","volume":"89","author":"Pacheco","year":"2017","journal-title":"J. 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