Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria
Abstract Background Deep sequencing could improve understanding of HIV treatment failure and viral population dynamics. However, this tool is often inaccessible in low- and middle-income countries. Objectives To determine the genetic patterns of resistance emerging in West African HIV-1 subtypes dur...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2022-02, Vol.77 (2), p.474-482 |
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| creator | El Bouzidi, Kate Datir, Rawlings P. Kwaghe, Vivian Roy, Sunando Frampton, Dan Breuer, Judith Ogbanufe, Obinna Murtala-Ibrahim, Fati Charurat, Man Dakum, Patrick Sabin, Caroline A. Ndembi, Nicaise Gupta, Ravindra K. |
| description | Abstract
Background
Deep sequencing could improve understanding of HIV treatment failure and viral population dynamics. However, this tool is often inaccessible in low- and middle-income countries.
Objectives
To determine the genetic patterns of resistance emerging in West African HIV-1 subtypes during first-line virological failure, and the implications for future antiretroviral options.
Patients and methods
Participants were selected from a Nigerian cohort of people living with HIV who had failed first-line ART and subsequently switched to second-line therapy. Whole HIV-1 genome sequences were generated from first-line virological failure samples with Illumina MiSeq. Mutations detected at ≥2% frequency were analysed and compared by subtype.
Results
HIV-1 sequences were obtained from 101 participants (65% female, median age 30 years, median 32.9 months of nevirapine- or efavirenz-based ART). Thymidine analogue mutations (TAMs) were detected in 61%, other core NRTI mutations in 92% and NNRTI mutations in 99%. Minority variants ( |
| doi_str_mv | 10.1093/jac/dkab385 |
| format | Article |
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Background
Deep sequencing could improve understanding of HIV treatment failure and viral population dynamics. However, this tool is often inaccessible in low- and middle-income countries.
Objectives
To determine the genetic patterns of resistance emerging in West African HIV-1 subtypes during first-line virological failure, and the implications for future antiretroviral options.
Patients and methods
Participants were selected from a Nigerian cohort of people living with HIV who had failed first-line ART and subsequently switched to second-line therapy. Whole HIV-1 genome sequences were generated from first-line virological failure samples with Illumina MiSeq. Mutations detected at ≥2% frequency were analysed and compared by subtype.
Results
HIV-1 sequences were obtained from 101 participants (65% female, median age 30 years, median 32.9 months of nevirapine- or efavirenz-based ART). Thymidine analogue mutations (TAMs) were detected in 61%, other core NRTI mutations in 92% and NNRTI mutations in 99%. Minority variants (<20% frequency) comprised 18% of all mutations. K65R was more prevalent in CRF02_AG than G subtypes (33% versus 7%; P = 0.002), and ≥3 TAMs were more common in G than CRF02_AG (52% versus 24%; P = 0.004). Subtype G viruses also contained more RT cleavage site mutations. Cross-resistance to at least one of the newer NNRTIs, doravirine, etravirine or rilpivirine, was predicted in 81% of participants.
Conclusions
Extensive drug resistance had accumulated in people with West African HIV-1 subtypes, prior to second-line ART. Deep sequencing significantly increased the detection of resistance-associated mutations. Caution should be used if considering newer-generation NNRTI agents in this setting.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkab385</identifier><identifier>PMID: 34741609</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adult ; Anti-HIV Agents - pharmacology ; Anti-HIV Agents - therapeutic use ; Drug Resistance, Viral - genetics ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; HIV Infections - drug therapy ; HIV-1 - genetics ; Humans ; Male ; Mutation ; Nigeria ; Original Research ; Treatment Failure ; Viral Load</subject><ispartof>Journal of antimicrobial chemotherapy, 2022-02, Vol.77 (2), p.474-482</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-a4de7e54c0959db4ada02c6c7aca37831c8777bb6d5e31730fc569b9d936fc1f3</citedby><cites>FETCH-LOGICAL-c412t-a4de7e54c0959db4ada02c6c7aca37831c8777bb6d5e31730fc569b9d936fc1f3</cites><orcidid>0000-0002-3614-4570</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34741609$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El Bouzidi, Kate</creatorcontrib><creatorcontrib>Datir, Rawlings P.</creatorcontrib><creatorcontrib>Kwaghe, Vivian</creatorcontrib><creatorcontrib>Roy, Sunando</creatorcontrib><creatorcontrib>Frampton, Dan</creatorcontrib><creatorcontrib>Breuer, Judith</creatorcontrib><creatorcontrib>Ogbanufe, Obinna</creatorcontrib><creatorcontrib>Murtala-Ibrahim, Fati</creatorcontrib><creatorcontrib>Charurat, Man</creatorcontrib><creatorcontrib>Dakum, Patrick</creatorcontrib><creatorcontrib>Sabin, Caroline A.</creatorcontrib><creatorcontrib>Ndembi, Nicaise</creatorcontrib><creatorcontrib>Gupta, Ravindra K.</creatorcontrib><title>Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Abstract
Background
Deep sequencing could improve understanding of HIV treatment failure and viral population dynamics. However, this tool is often inaccessible in low- and middle-income countries.
Objectives
To determine the genetic patterns of resistance emerging in West African HIV-1 subtypes during first-line virological failure, and the implications for future antiretroviral options.
Patients and methods
Participants were selected from a Nigerian cohort of people living with HIV who had failed first-line ART and subsequently switched to second-line therapy. Whole HIV-1 genome sequences were generated from first-line virological failure samples with Illumina MiSeq. Mutations detected at ≥2% frequency were analysed and compared by subtype.
Results
HIV-1 sequences were obtained from 101 participants (65% female, median age 30 years, median 32.9 months of nevirapine- or efavirenz-based ART). Thymidine analogue mutations (TAMs) were detected in 61%, other core NRTI mutations in 92% and NNRTI mutations in 99%. Minority variants (<20% frequency) comprised 18% of all mutations. K65R was more prevalent in CRF02_AG than G subtypes (33% versus 7%; P = 0.002), and ≥3 TAMs were more common in G than CRF02_AG (52% versus 24%; P = 0.004). Subtype G viruses also contained more RT cleavage site mutations. Cross-resistance to at least one of the newer NNRTIs, doravirine, etravirine or rilpivirine, was predicted in 81% of participants.
Conclusions
Extensive drug resistance had accumulated in people with West African HIV-1 subtypes, prior to second-line ART. Deep sequencing significantly increased the detection of resistance-associated mutations. Caution should be used if considering newer-generation NNRTI agents in this setting.</description><subject>Adult</subject><subject>Anti-HIV Agents - pharmacology</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Drug Resistance, Viral - genetics</subject><subject>Female</subject><subject>Genotype</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>HIV Infections - drug therapy</subject><subject>HIV-1 - genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Mutation</subject><subject>Nigeria</subject><subject>Original Research</subject><subject>Treatment Failure</subject><subject>Viral Load</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kc1u1TAQRi0EopfCij3yCiGhUDuO43iDhMpPK1WwAbbWxJkEl1w72E5En4JXxtW9VLBh5cUcnxl9HyFPOXvFmRZn12DPhu_Qi07eIzvetKyqmeb3yY4JJivVSHFCHqV0zRhrZds9JCeiUQ1vmd6RX28RF5rwx4reOj_RMNKLy68VpxE3hDlR_JnRJ7chTWufbxakG0QH2QVPwQ90iOtU4ORSBm-Rwpgx0hHcvEa81Y0uplzNzpeZzy5ijmFzEebya3L7IqfO049uwqJ9TB6MZSs-Ob6n5Mv7d5_PL6qrTx8uz99cVbbhda6gGVChbCzTUg99AwOw2rZWgQWhOsFtp5Tq-3aQKLgSbLSy1b0etGhHy0dxSl4fvMva73Gw6HO5yCzR7SHemADO_Dvx7puZwma6rmTbdUXw4iiIoYSXstm7ZHGewWNYk6mlbmrdlqAL-vKA2hhSijjereHM3FZoSoXmWGGhn_192R37p7MCPD8AYV3-a_oNTOOqKg</recordid><startdate>20220202</startdate><enddate>20220202</enddate><creator>El Bouzidi, Kate</creator><creator>Datir, Rawlings P.</creator><creator>Kwaghe, Vivian</creator><creator>Roy, Sunando</creator><creator>Frampton, Dan</creator><creator>Breuer, Judith</creator><creator>Ogbanufe, Obinna</creator><creator>Murtala-Ibrahim, Fati</creator><creator>Charurat, Man</creator><creator>Dakum, Patrick</creator><creator>Sabin, Caroline A.</creator><creator>Ndembi, Nicaise</creator><creator>Gupta, Ravindra K.</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3614-4570</orcidid></search><sort><creationdate>20220202</creationdate><title>Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria</title><author>El Bouzidi, Kate ; Datir, Rawlings P. ; Kwaghe, Vivian ; Roy, Sunando ; Frampton, Dan ; Breuer, Judith ; Ogbanufe, Obinna ; Murtala-Ibrahim, Fati ; Charurat, Man ; Dakum, Patrick ; Sabin, Caroline A. ; Ndembi, Nicaise ; Gupta, Ravindra K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-a4de7e54c0959db4ada02c6c7aca37831c8777bb6d5e31730fc569b9d936fc1f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>Anti-HIV Agents - pharmacology</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Drug Resistance, Viral - genetics</topic><topic>Female</topic><topic>Genotype</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>HIV Infections - drug therapy</topic><topic>HIV-1 - genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Mutation</topic><topic>Nigeria</topic><topic>Original Research</topic><topic>Treatment Failure</topic><topic>Viral Load</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El Bouzidi, Kate</creatorcontrib><creatorcontrib>Datir, Rawlings P.</creatorcontrib><creatorcontrib>Kwaghe, Vivian</creatorcontrib><creatorcontrib>Roy, Sunando</creatorcontrib><creatorcontrib>Frampton, Dan</creatorcontrib><creatorcontrib>Breuer, Judith</creatorcontrib><creatorcontrib>Ogbanufe, Obinna</creatorcontrib><creatorcontrib>Murtala-Ibrahim, Fati</creatorcontrib><creatorcontrib>Charurat, Man</creatorcontrib><creatorcontrib>Dakum, Patrick</creatorcontrib><creatorcontrib>Sabin, Caroline A.</creatorcontrib><creatorcontrib>Ndembi, Nicaise</creatorcontrib><creatorcontrib>Gupta, Ravindra K.</creatorcontrib><collection>Access via Oxford University Press (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El Bouzidi, Kate</au><au>Datir, Rawlings P.</au><au>Kwaghe, Vivian</au><au>Roy, Sunando</au><au>Frampton, Dan</au><au>Breuer, Judith</au><au>Ogbanufe, Obinna</au><au>Murtala-Ibrahim, Fati</au><au>Charurat, Man</au><au>Dakum, Patrick</au><au>Sabin, Caroline A.</au><au>Ndembi, Nicaise</au><au>Gupta, Ravindra K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2022-02-02</date><risdate>2022</risdate><volume>77</volume><issue>2</issue><spage>474</spage><epage>482</epage><pages>474-482</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><abstract>Abstract
Background
Deep sequencing could improve understanding of HIV treatment failure and viral population dynamics. However, this tool is often inaccessible in low- and middle-income countries.
Objectives
To determine the genetic patterns of resistance emerging in West African HIV-1 subtypes during first-line virological failure, and the implications for future antiretroviral options.
Patients and methods
Participants were selected from a Nigerian cohort of people living with HIV who had failed first-line ART and subsequently switched to second-line therapy. Whole HIV-1 genome sequences were generated from first-line virological failure samples with Illumina MiSeq. Mutations detected at ≥2% frequency were analysed and compared by subtype.
Results
HIV-1 sequences were obtained from 101 participants (65% female, median age 30 years, median 32.9 months of nevirapine- or efavirenz-based ART). Thymidine analogue mutations (TAMs) were detected in 61%, other core NRTI mutations in 92% and NNRTI mutations in 99%. Minority variants (<20% frequency) comprised 18% of all mutations. K65R was more prevalent in CRF02_AG than G subtypes (33% versus 7%; P = 0.002), and ≥3 TAMs were more common in G than CRF02_AG (52% versus 24%; P = 0.004). Subtype G viruses also contained more RT cleavage site mutations. Cross-resistance to at least one of the newer NNRTIs, doravirine, etravirine or rilpivirine, was predicted in 81% of participants.
Conclusions
Extensive drug resistance had accumulated in people with West African HIV-1 subtypes, prior to second-line ART. Deep sequencing significantly increased the detection of resistance-associated mutations. Caution should be used if considering newer-generation NNRTI agents in this setting.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>34741609</pmid><doi>10.1093/jac/dkab385</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3614-4570</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adult Anti-HIV Agents - pharmacology Anti-HIV Agents - therapeutic use Drug Resistance, Viral - genetics Female Genotype High-Throughput Nucleotide Sequencing HIV Infections - drug therapy HIV-1 - genetics Humans Male Mutation Nigeria Original Research Treatment Failure Viral Load |
| title | Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria |
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