{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:11:51Z","timestamp":1787663511721,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UK Medical Research Council (MRC)"},{"name":"UK Department for International Development (DFID)"},{"name":"European Union"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>We assessed the performance and clinical relevance of Illumina MiSeq next-generation sequencing (NGS) for HIV-1 genotyping compared with Sanger sequencing (SS). We analyzed 167 participants, 45 with virologic failure (VL \u2265 1000 copies\/mL), i.e., cases, and 122 time-matched participants with virologic suppression (VL &lt; 1000 copies\/mL), i.e., controls, 12 months post-ART initiation. Major surveillance drug resistance mutations (SDRMs) detected by SS were all detectable by NGS. Among cases at 12 months, SS identified SDRMs in 32\/45 (71.1%) while NGS identified SDRMs among 35\/45 (77.8%), increasing the number of cases with SDRMs by 3\/45 (6.7%). Participants identified with, and proportions of major SDRMs increased when NGS was used. NGS vs. SS at endpoint revealed for NNRTIs: 36\/45 vs. 33\/45; Y181C: 26\/45 vs. 24\/45; K103N: 9\/45 vs. 6\/45 participants with SDRMs, respectively. At baseline, NGS revealed major SDRMs in 9\/45 (20%) cases without SDRMs by SS. Participant MBL\/043, among the nine, the following major SDRMs existed: L90M to PIs, K65R and M184V to NRTIs, and Y181C and K103N to NNRTIs. The SDRMs among the nine increased SDRMs to NRTIs, NNRTIs, and PIs. Only 43\/122 (25.7%) of participants had pre-treatment minority SDRMs. Also, 24.4% of the cases vs. 26.2 of controls had minority SDRMs (p = 0.802); minority SDRMs were not associated with virologic failure. NGS agreed with SS in HIV-1 genotyping but detected additional major SDRMs and identified more participants harboring major SDRMs, expanding the HIV DRM profile of this cohort. NGS could improve HIV genotyping to guide treatment decisions for enhancing ART efficacy, a cardinal pre-requisite in the pursuit of the UNAIDS 95-95-95 targets.<\/jats:p>","DOI":"10.3390\/v16091454","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T03:03:37Z","timestamp":1726196617000},"page":"1454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Next-Generation Sequencing Reveals a High Frequency of HIV-1 Minority Variants and an Expanded Drug Resistance Profile among Individuals on First-Line ART"],"prefix":"10.3390","volume":"16","author":[{"given":"Maria","family":"Nannyonjo","sequence":"first","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonah","family":"Omooja","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"},{"name":"Uganda Virus Research Institute, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Lule","family":"Bugembe","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Bbosa","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Lunkuse","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella Esther","family":"Nabirye","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1793-0444","authenticated-orcid":false,"given":"Faridah","family":"Nassolo","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamidah","family":"Namagembe","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Abaasa","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kazibwe","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, College of Veterinary Medicine, Makerere University, Kampala P.O. Box 7072, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontiano","family":"Kaleebu","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"},{"name":"Uganda Virus Research Institute, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9675-4234","authenticated-orcid":false,"given":"Deogratius","family":"Ssemwanga","sequence":"additional","affiliation":[{"name":"Medical Research Council\/Uganda Virus Research Institute & London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe P.O. Box 49, Uganda"},{"name":"Uganda Virus Research Institute, Entebbe P.O. Box 49, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"ref_1","unstructured":"(2024, June 01). UNAIDS DATA 2022. Geneva: Joint United Nations Program on HIV\/AIDS. Available online: https:\/\/www.unaids.org\/sites\/default\/files\/media_asset\/data-book-2022_en.pdf."},{"key":"ref_2","unstructured":"McMahon, R. (2014). UNAIDS Issues New Fast-Track Strategy to End AIDS by 2030-EGPAF, Elizabeth Glaser Pediatric AIDS Foundation. Available online: https:\/\/www.pedaids.org\/2014\/11\/20\/unaids-issues-new-fast-track-strategy-to-end-aids-by-2030."},{"key":"ref_3","unstructured":"(2017, September 05). WHO Surveillance of HIV Drug Resistance in Adults Receiving ART (Acquired HIV Drug Resistance). 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