{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:52:54Z","timestamp":1790031174162,"version":"4.0.1"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T00:00:00Z","timestamp":1562889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Janssen"},{"name":"University of Liverpool and Chantal Biya International Reference Centre"},{"name":"CIRCB"},{"DOI":"10.13039\/501100000836","name":"University of Liverpool","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000836","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In sub-Saharan Africa, detecting resistance-associated mutations (RAMs) at failure of first-line ART with two NRTIs plus an NNRTI predicts improved virological responses to second-line therapy with two NRTIs plus a ritonavir-boosted PI (PI\/r). This indicates residual NRTI activity in the presence of RAMs, although additional factors may contribute to the effect.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The aim of this study was to investigate the influence of pre-existing RAMs on the outcomes of maintenance monotherapy with ritonavir-boosted darunavir within a randomized trial in Cameroon.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>RAMs were detected in HIV-1 DNA using PBMCs collected at initiation of darunavir\/ritonavir monotherapy. Adherence was assessed by pill count and visual analogue scale (VAS). Predictors of virological failure (confirmed or last available viral load &amp;gt;400 copies\/mL) were explored by logistic regression analysis. Trial name\u205f=\u205fMANET (NCT02155101).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>After NNRTI-based therapy, participants (n\u205f=\u205f81) had received PI\/r-based therapy for a median of 3.2\u2009years and had a confirmed viral load &amp;lt;60 copies\/mL and a median CD4 count of 466\u2009cells\/mm3. NRTI and NNRTI RAMs were detected in 39\/60 (65.0%) and 41\/60 (68.3%) HIV-1 DNA sequences, respectively. Over 48\u2009weeks of monotherapy, 16\/81 (19.8%) patients experienced virological failure. After adjusting for age, HIV-1 DNA load, adherence by VAS and RAM status, virological failure was less likely with higher VAS-measured adherence (adjusted OR 0.04, 95% CI 0.01\u20130.37; P\u205f=\u205f0.004) and detectable HIV-1 DNA RAMs (adjusted OR 0.15, 95% CI 0.03\u20130.82; P\u205f=\u205f0.028).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Pre-existing NRTI and NNRTI RAMs are associated with improved virological responses to NRTI-sparing ART in sub-Saharan Africa, indicating a predictive effect that is independent of residual NRTI activity.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkz264","type":"journal-article","created":{"date-parts":[[2019,6,14]],"date-time":"2019-06-14T12:12:12Z","timestamp":1560514332000},"page":"3011-3015","source":"Crossref","is-referenced-by-count":12,"title":["An apparent paradox: resistance mutations in HIV-1 DNA predict improved virological responses to antiretroviral therapy"],"prefix":"10.1093","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3670-6588","authenticated-orcid":false,"given":"Anna Maria","family":"Geretti","sequence":"first","affiliation":[{"name":"Institute of Infection & Global Health , University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Abdullahi","sequence":"additional","affiliation":[{"name":"Institute of Infection & Global Health , University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Mafotsing Fopoussi","sequence":"additional","affiliation":[{"name":"Institute of Infection & Global Health , University of Liverpool, Liverpool, UK"},{"name":"Chantal Biya International Reference Centre for Research on HIV\/AIDS Prevention & Management (CIRCB), Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bonnett","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine , University of Liverpool, Liverpool, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoire","family":"Fokom Defo","sequence":"additional","affiliation":[{"name":"Chantal Biya International Reference Centre for Research on HIV\/AIDS Prevention & Management (CIRCB), Yaound\u00e9, Cameroon"},{"name":"Ministry of Public Health H\u00f4pital Central Yaound\u00e9, , Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Moudourou","sequence":"additional","affiliation":[{"name":"Chantal Biya International Reference Centre for Research on HIV\/AIDS Prevention & Management (CIRCB), Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Fokam","sequence":"additional","affiliation":[{"name":"Chantal Biya International Reference Centre for Research on HIV\/AIDS Prevention & Management (CIRCB), Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Kouanfack","sequence":"additional","affiliation":[{"name":"Ministry of Public Health H\u00f4pital Central Yaound\u00e9, , Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Torimiro","sequence":"additional","affiliation":[{"name":"Chantal Biya International Reference Centre for Research on HIV\/AIDS Prevention & Management (CIRCB), Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,12]]},"reference":[{"key":"2024082905351567100_dkz264-B1"},{"key":"2024082905351567100_dkz264-B2","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1001\/jama.296.6.679","article-title":"Adherence to antiretroviral therapy in sub-Saharan Africa and North America","volume":"296","author":"Mills","year":"2006","journal-title":"JAMA"},{"key":"2024082905351567100_dkz264-B3","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1007\/s10461-011-9942-x","article-title":"Adherence to highly active antiretroviral therapy (HAART): a meta-analysis","volume":"15","author":"Ortego","year":"2011","journal-title":"AIDS Behav"},{"key":"2024082905351567100_dkz264-B4","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1093\/cid\/civ556","article-title":"Long-term virological outcomes of first-line antiretroviral therapy for HIV-1 in low- and middle-income countries: a systematic review and meta-analysis","volume":"61","author":"Boender","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2024082905351567100_dkz264-B5","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/cid\/cix1108","article-title":"Effectiveness of protease inhibitor\/nucleos(t)ide reverse transcriptase inhibitor-based second-line antiretroviral therapy for the treatment of HIV-1 infection in sub-Saharan Africa: a systematic review and meta-analysis","volume":"66","author":"Stockdale","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2024082905351567100_dkz264-B6","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1093\/cid\/cis254","article-title":"Patterns of HIV-1 drug resistance after first-line antiretroviral therapy (ART) failure in 6 sub-Saharan African countries: implications for second-line ART strategies","volume":"54","author":"Hamers","year":"2012","journal-title":"Clin Infect Dis"},{"key":"2024082905351567100_dkz264-B7","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1089\/aid.2015.0331","article-title":"Antiretroviral resistance after first-line antiretroviral therapy failure in diverse HIV-1 subtypes in the SECOND-LINE study","volume":"32","author":"Lam","year":"2016","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2024082905351567100_dkz264-B8","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S1473-3099(15)00536-8","article-title":"Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study","volume":"16","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"2024082905351567100_dkz264-B9","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1089\/aid.2016.0010","article-title":"High viral load and multidrug resistance due to late switch to second-line regimens could be a major obstacle to reach the 90-90-90 UNAIDS","volume":"32","author":"Guichet","year":"2016","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2024082905351567100_dkz264-B10","doi-asserted-by":"crossref","first-page":"3148","DOI":"10.1093\/jac\/dky281","article-title":"Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring","volume":"73","author":"Villa","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"2024082905351567100_dkz264-B11","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1089\/aid.2017.0290","article-title":"Nucleoside reverse transcriptase inhibitors with reduced predicted activity do not impair second-line therapy with lopinavir\/ritonavir or darunavir\/ritonavir","volume":"34","author":"Villabona-Arenas","year":"2018","journal-title":"AIDS Res Hum Retroviruses"},{"key":"2024082905351567100_dkz264-B12","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.ebiom.2015.07.025","article-title":"During stably suppressive antiretroviral therapy integrated HIV-1 DNA load in peripheral blood is associated with the frequency of CD8 cells expressing HLA-DR\/DP\/DQ","volume":"2","author":"Ruggiero","year":"2015","journal-title":"EBioMedicine"},{"key":"2024082905351567100_dkz264-B13","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1093\/jac\/dkt474","article-title":"Sensitive testing of plasma HIV-1 RNA and Sanger sequencing of cellular HIV-1 DNA for the detection of drug resistance prior to starting first-line antiretroviral therapy with etravirine or efavirenz","volume":"69","author":"Geretti","year":"2014","journal-title":"J Antimicrob Chemother"},{"key":"2024082905351567100_dkz264-B14","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/hiv.12348","article-title":"Efficacy of protease inhibitor monotherapy vs. triple therapy: meta-analysis of data from 2303 patients in 13 randomized trials","volume":"17","author":"Arribas","year":"2016","journal-title":"HIV Med"},{"key":"2024082905351567100_dkz264-B15","doi-asserted-by":"crossref","first-page":"e384","DOI":"10.1016\/S2352-3018(17)30069-3","article-title":"Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286\/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial","volume":"4","author":"Ciaffi","year":"2017","journal-title":"Lancet HIV"},{"key":"2024082905351567100_dkz264-B16","article-title":"Evolution of protease inhibitor resistance in human immunodeficiency virus type 1 infected patients failing protease inhibitor monotherapy as second-line therapy in low-income countries: an observational analysis within the EARNEST randomized trial","author":"Thompson","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2024082905351567100_dkz264-B17","doi-asserted-by":"crossref","first-page":"ofy251.","DOI":"10.1093\/ofid\/ofy251","article-title":"Hepatitis B virus (HBV) infection and re-activation during nucleos(t)ide reverse transcriptase inhibitor-sparing antiretroviral therapy in a high-HBV endemicity setting","volume":"5","author":"Abdullahi","year":"2018","journal-title":"Open Forum Infect Dis"},{"key":"2024082905351567100_dkz264-B18","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12981-017-0138-y","article-title":"Comparison of six methods to estimate adherence in an ART-naive cohort in a resource-poor setting: which best predicts virological and resistance outcomes?","volume":"14","author":"Orrell","year":"2017","journal-title":"AIDS Res Ther"},{"key":"2024082905351567100_dkz264-B19","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1097\/QAD.0000000000001206","article-title":"Factors associated with virological rebound in HIV-infected patients receiving protease inhibitor monotherapy","volume":"30","author":"St\u00f6hr","year":"2016","journal-title":"AIDS"},{"key":"2024082905351567100_dkz264-B20","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1093\/infdis\/jir518","article-title":"Factors associated with virological failure in HIV-1-infected patients receiving darunavir\/ritonavir monotherapy","volume":"204","author":"Lambert-Niclot","year":"2011","journal-title":"J Infect Dis"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/74\/10\/3011\/58958360\/jac_74_10_3011.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/74\/10\/3011\/58958360\/jac_74_10_3011.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T05:35:37Z","timestamp":1724909737000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/74\/10\/3011\/5531805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,12]]},"references-count":20,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,7,12]]},"published-print":{"date-parts":[[2019,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkz264","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,10]]},"published":{"date-parts":[[2019,7,12]]}}}