Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania

Abstract Background More than 15 million people in sub-Saharan Africa receive ART. Treatment failure is common, but the role of HIV drug resistance in treatment failure is largely unknown because drug resistance testing is not routinely done. This study determined the prevalence and patterns of HIV...

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Veröffentlicht in:Journal of antimicrobial chemotherapy 2022-02, Vol.77 (2), p.483-491
Hauptverfasser: Henerico, Shimba, Mikasi, Sello Given, Kalluvya, Samuel Elias, Brauner, Jan M., Abdul, Seif, Lyimo, Eric, Desderius, Bernard, Korn, Klaus, van Zyl, Gert, Jacobs, Graeme Brendon, Preiser, Wolfgang, Kasang, Christa
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container_end_page 491
container_issue 2
container_start_page 483
container_title Journal of antimicrobial chemotherapy
container_volume 77
creator Henerico, Shimba
Mikasi, Sello Given
Kalluvya, Samuel Elias
Brauner, Jan M.
Abdul, Seif
Lyimo, Eric
Desderius, Bernard
Korn, Klaus
van Zyl, Gert
Jacobs, Graeme Brendon
Preiser, Wolfgang
Kasang, Christa
description Abstract Background More than 15 million people in sub-Saharan Africa receive ART. Treatment failure is common, but the role of HIV drug resistance in treatment failure is largely unknown because drug resistance testing is not routinely done. This study determined the prevalence and patterns of HIV drug resistance in patients with suspected virological failure. Materials and methods A single high viral load of >1000 viral RNA copies/mL of plasma at any point during ART was considered as suspected virological failure. HIV-1 RNA was extracted from plasma samples of these patients using the QIAamp Viral RNA kit. The protease and part of the RT regions of the HIV pol gene were characterized. Results Viral load was determined in 317 patients; 64 (20.2%) had suspected virological failure. We successfully genotyped 56 samples; 48 (85.7%) had at least one major resistance-associated mutation (RAM). Common mutations in RT were M184V (75%), T215Y (41.1%), K103N (39.3%), M41L (32.1%), D67DN (30.3%), G190A (28.6%) and A98G (26.8%). No RAMs were detected in ART regimens based on a ritonavir-boosted PI. Conclusions The Tanzanian national guidelines define ‘virological failure’ as two consecutive viral load measurement results, at 3 month intervals, above the WHO threshold (1000 copies/mL). Here, we show that a single viral load above the WHO threshold is associated with high rates of RAMs. This suggests that a single high viral load measurement could be used to predict virological failure and avoid delays in switching patients from first-line to higher genetic barrier second-line regimens.
doi_str_mv 10.1093/jac/dkab406
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Treatment failure is common, but the role of HIV drug resistance in treatment failure is largely unknown because drug resistance testing is not routinely done. This study determined the prevalence and patterns of HIV drug resistance in patients with suspected virological failure. Materials and methods A single high viral load of &gt;1000 viral RNA copies/mL of plasma at any point during ART was considered as suspected virological failure. HIV-1 RNA was extracted from plasma samples of these patients using the QIAamp Viral RNA kit. The protease and part of the RT regions of the HIV pol gene were characterized. Results Viral load was determined in 317 patients; 64 (20.2%) had suspected virological failure. We successfully genotyped 56 samples; 48 (85.7%) had at least one major resistance-associated mutation (RAM). Common mutations in RT were M184V (75%), T215Y (41.1%), K103N (39.3%), M41L (32.1%), D67DN (30.3%), G190A (28.6%) and A98G (26.8%). No RAMs were detected in ART regimens based on a ritonavir-boosted PI. Conclusions The Tanzanian national guidelines define ‘virological failure’ as two consecutive viral load measurement results, at 3 month intervals, above the WHO threshold (1000 copies/mL). Here, we show that a single viral load above the WHO threshold is associated with high rates of RAMs. This suggests that a single high viral load measurement could be used to predict virological failure and avoid delays in switching patients from first-line to higher genetic barrier second-line regimens.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkab406</identifier><identifier>PMID: 35107140</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Anti-HIV Agents - pharmacology ; Anti-HIV Agents - therapeutic use ; Drug Resistance, Viral - genetics ; HIV Infections - drug therapy ; HIV Infections - epidemiology ; HIV-1 - genetics ; Humans ; Original Research ; Prevalence ; Tanzania - epidemiology ; Treatment Failure ; Viral Load</subject><ispartof>Journal of antimicrobial chemotherapy, 2022-02, Vol.77 (2), p.483-491</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-8e464d8876b420d3d89c189a52bd1cf14fc706fee9e57577bc80e411b4e664613</citedby><cites>FETCH-LOGICAL-c412t-8e464d8876b420d3d89c189a52bd1cf14fc706fee9e57577bc80e411b4e664613</cites><orcidid>0000-0003-0241-0321 ; 0000-0002-0254-7910 ; 0000-0003-3021-5101 ; 0000-0003-3659-0615</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35107140$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Henerico, Shimba</creatorcontrib><creatorcontrib>Mikasi, Sello Given</creatorcontrib><creatorcontrib>Kalluvya, Samuel Elias</creatorcontrib><creatorcontrib>Brauner, Jan M.</creatorcontrib><creatorcontrib>Abdul, Seif</creatorcontrib><creatorcontrib>Lyimo, Eric</creatorcontrib><creatorcontrib>Desderius, Bernard</creatorcontrib><creatorcontrib>Korn, Klaus</creatorcontrib><creatorcontrib>van Zyl, Gert</creatorcontrib><creatorcontrib>Jacobs, Graeme Brendon</creatorcontrib><creatorcontrib>Preiser, Wolfgang</creatorcontrib><creatorcontrib>Kasang, Christa</creatorcontrib><title>Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Abstract Background More than 15 million people in sub-Saharan Africa receive ART. Treatment failure is common, but the role of HIV drug resistance in treatment failure is largely unknown because drug resistance testing is not routinely done. This study determined the prevalence and patterns of HIV drug resistance in patients with suspected virological failure. Materials and methods A single high viral load of &gt;1000 viral RNA copies/mL of plasma at any point during ART was considered as suspected virological failure. HIV-1 RNA was extracted from plasma samples of these patients using the QIAamp Viral RNA kit. The protease and part of the RT regions of the HIV pol gene were characterized. Results Viral load was determined in 317 patients; 64 (20.2%) had suspected virological failure. We successfully genotyped 56 samples; 48 (85.7%) had at least one major resistance-associated mutation (RAM). Common mutations in RT were M184V (75%), T215Y (41.1%), K103N (39.3%), M41L (32.1%), D67DN (30.3%), G190A (28.6%) and A98G (26.8%). No RAMs were detected in ART regimens based on a ritonavir-boosted PI. Conclusions The Tanzanian national guidelines define ‘virological failure’ as two consecutive viral load measurement results, at 3 month intervals, above the WHO threshold (1000 copies/mL). Here, we show that a single viral load above the WHO threshold is associated with high rates of RAMs. This suggests that a single high viral load measurement could be used to predict virological failure and avoid delays in switching patients from first-line to higher genetic barrier second-line regimens.</description><subject>Anti-HIV Agents - pharmacology</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Drug Resistance, Viral - genetics</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - epidemiology</subject><subject>HIV-1 - genetics</subject><subject>Humans</subject><subject>Original Research</subject><subject>Prevalence</subject><subject>Tanzania - epidemiology</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>eNp9kU1P3DAQhq2qqGxpT9yRT1WlKmAnjuNckCrUAhKiPdD2aE3sya5p1k7tZFH59STsgsqlpznMo2c-XkIOOTvmrC5ObsGc2N_QCCZfkQUXkmU5q_lrsmAFK7NKlMU-eZvSLWNMllK9IftFyVnFBVuQu-8RN9ChN0jBW9rDMGD0iYaWXlz-pDaOSxoxuTTAzDg_Iw79kOidG1Y0jalHM6ClGxdDF5bOQEdbcN0YH_HrEIdV9gvT7KU34O_BO3hH9lroEr7f1QPy4-uXm7OL7Orb-eXZ56vMCJ4PmUIhhVWqko3ImS2sqg1XNZR5Y7lpuWhNxWSLWGNZlVXVGMVQcN4IlFJIXhyQ0623H5s1WjMtHqHTfXRriH91AKdfdrxb6WXYaKWmHyo5CT7uBDH8Gacr9Nolg10HHsOYdC5zUQtV5vOsT1vUxJBSxPZ5DGd6jkpPUeldVBN99O9mz-xTNhPwYQuEsf-v6QHN5qAk</recordid><startdate>20220202</startdate><enddate>20220202</enddate><creator>Henerico, Shimba</creator><creator>Mikasi, Sello Given</creator><creator>Kalluvya, Samuel Elias</creator><creator>Brauner, Jan M.</creator><creator>Abdul, Seif</creator><creator>Lyimo, Eric</creator><creator>Desderius, Bernard</creator><creator>Korn, Klaus</creator><creator>van Zyl, Gert</creator><creator>Jacobs, Graeme Brendon</creator><creator>Preiser, Wolfgang</creator><creator>Kasang, Christa</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/0000-0003-0241-0321</orcidid><orcidid>https://orcid.org/0000-0002-0254-7910</orcidid><orcidid>https://orcid.org/0000-0003-3021-5101</orcidid><orcidid>https://orcid.org/0000-0003-3659-0615</orcidid></search><sort><creationdate>20220202</creationdate><title>Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania</title><author>Henerico, Shimba ; Mikasi, Sello Given ; Kalluvya, Samuel Elias ; Brauner, Jan M. ; Abdul, Seif ; Lyimo, Eric ; Desderius, Bernard ; Korn, Klaus ; van Zyl, Gert ; Jacobs, Graeme Brendon ; Preiser, Wolfgang ; Kasang, Christa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-8e464d8876b420d3d89c189a52bd1cf14fc706fee9e57577bc80e411b4e664613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Anti-HIV Agents - pharmacology</topic><topic>Anti-HIV Agents - therapeutic use</topic><topic>Drug Resistance, Viral - genetics</topic><topic>HIV Infections - drug therapy</topic><topic>HIV Infections - epidemiology</topic><topic>HIV-1 - genetics</topic><topic>Humans</topic><topic>Original Research</topic><topic>Prevalence</topic><topic>Tanzania - epidemiology</topic><topic>Treatment Failure</topic><topic>Viral Load</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Henerico, Shimba</creatorcontrib><creatorcontrib>Mikasi, Sello Given</creatorcontrib><creatorcontrib>Kalluvya, Samuel Elias</creatorcontrib><creatorcontrib>Brauner, Jan M.</creatorcontrib><creatorcontrib>Abdul, Seif</creatorcontrib><creatorcontrib>Lyimo, Eric</creatorcontrib><creatorcontrib>Desderius, Bernard</creatorcontrib><creatorcontrib>Korn, Klaus</creatorcontrib><creatorcontrib>van Zyl, Gert</creatorcontrib><creatorcontrib>Jacobs, Graeme Brendon</creatorcontrib><creatorcontrib>Preiser, Wolfgang</creatorcontrib><creatorcontrib>Kasang, Christa</creatorcontrib><collection>Oxford Journals 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>Henerico, Shimba</au><au>Mikasi, Sello Given</au><au>Kalluvya, Samuel Elias</au><au>Brauner, Jan M.</au><au>Abdul, Seif</au><au>Lyimo, Eric</au><au>Desderius, Bernard</au><au>Korn, Klaus</au><au>van Zyl, Gert</au><au>Jacobs, Graeme Brendon</au><au>Preiser, Wolfgang</au><au>Kasang, Christa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania</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>483</spage><epage>491</epage><pages>483-491</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><abstract>Abstract Background More than 15 million people in sub-Saharan Africa receive ART. Treatment failure is common, but the role of HIV drug resistance in treatment failure is largely unknown because drug resistance testing is not routinely done. This study determined the prevalence and patterns of HIV drug resistance in patients with suspected virological failure. Materials and methods A single high viral load of &gt;1000 viral RNA copies/mL of plasma at any point during ART was considered as suspected virological failure. HIV-1 RNA was extracted from plasma samples of these patients using the QIAamp Viral RNA kit. The protease and part of the RT regions of the HIV pol gene were characterized. Results Viral load was determined in 317 patients; 64 (20.2%) had suspected virological failure. We successfully genotyped 56 samples; 48 (85.7%) had at least one major resistance-associated mutation (RAM). Common mutations in RT were M184V (75%), T215Y (41.1%), K103N (39.3%), M41L (32.1%), D67DN (30.3%), G190A (28.6%) and A98G (26.8%). No RAMs were detected in ART regimens based on a ritonavir-boosted PI. Conclusions The Tanzanian national guidelines define ‘virological failure’ as two consecutive viral load measurement results, at 3 month intervals, above the WHO threshold (1000 copies/mL). Here, we show that a single viral load above the WHO threshold is associated with high rates of RAMs. This suggests that a single high viral load measurement could be used to predict virological failure and avoid delays in switching patients from first-line to higher genetic barrier second-line regimens.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>35107140</pmid><doi>10.1093/jac/dkab406</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-0241-0321</orcidid><orcidid>https://orcid.org/0000-0002-0254-7910</orcidid><orcidid>https://orcid.org/0000-0003-3021-5101</orcidid><orcidid>https://orcid.org/0000-0003-3659-0615</orcidid><oa>free_for_read</oa></addata></record>
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection; Free Full-Text Journals in Chemistry
subjects Anti-HIV Agents - pharmacology
Anti-HIV Agents - therapeutic use
Drug Resistance, Viral - genetics
HIV Infections - drug therapy
HIV Infections - epidemiology
HIV-1 - genetics
Humans
Original Research
Prevalence
Tanzania - epidemiology
Treatment Failure
Viral Load
title Prevalence and patterns of HIV drug resistance in patients with suspected virological failure in North-Western Tanzania
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