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0-26.741-21.543-14.142-34.142l128.662-128.662c7.81-7.81 20.474-7.81 28.284 0l128.662 128.662c12.6 12.599 3.676 34.142-14.142 34.142z"></path></svg></button></li></ul></li></ul></div> <script src="//a.academia-assets.com/assets/webpack_bundles/fast_loswp-bundle-97865a4b41eebf6819eddc4c76d29598fe6b0336be57e9b6cde63060c39bfa02.js" defer="defer"></script><script>window.loswp = {}; window.loswp.author = 53252628; window.loswp.bulkDownloadFilterCounts = {}; window.loswp.hasDownloadableAttachment = true; window.loswp.hasViewableAttachments = true; // TODO: just use routes for this window.loswp.loginUrl = "https://www.academia.edu/login?post_login_redirect_url=https%3A%2F%2Fwww.academia.edu%2F53535922%2FTargeting_only_reverse_transcriptase_with_zidovudine_lamivudine_abacavir_plus_tenofovir_in_HIV_1_infected_patients_with_multidrug_resistant_virus_a_multicentre_pilot_study%3Fauto%3Ddownload"; window.loswp.translateUrl = 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with multidrug resistance receiving zidovudine/lamivudine/abacavir (TZV) plus tenofovir (TDF). Methods Pilot analysis of highly experienced patients (n 5 28), with ! 1 thymidine-associated mutation (TAM) and the M184V mutation. Results Median of 8.5 treatment regimens, 58% Centers for Disease Control stage C. Baseline (nadir) CD4 count 363 (112) cells/mL. There was a sustained 24-week drop in viral load (VL) of 0.71 HIV-1 RNA copies/mL (Po0.001), with 35.7% (10/28) achieving a VL of o50 copies/mL. The median 24-week decrease in CD4 was À 53 cells/mL and only À 17 cells/mL when baseline CD4 was o350 cells/mL. There was no evolution in RT mutations, TAMs, accessory mutations or K65R. No clinical progression and one out of 28 suspected abacavir Hypersensitivity Reaction (HSR). Lower probability of achieving VLo400 copies/mL was associated with D67N (P 5 0.007), D67N/M41L (P 5 0.01), ! 3 TAMs (P 5 0.07) and VL410 000 copies/mL (P 5 0.01). Mutations conferring zidovudine hypersusceptibility (Y181C, K65R and L74V) did not improve virological or immunological outcomes. Better CD4 outcomes were seen in patients without M41L (P 5 0.04) or with baseline VLo10 000 copies/mL (P 5 0.01). Conclusions A bridging regimen with TZV 1 TDF prevents significant immunological decline and may forestall viral evolution in HIV-1 RT despite persistent viral replication.","publication_date":"2008,,","publication_name":"HIV Medicine","grobid_abstract_attachment_id":"70334140"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Targeting only reverse transcriptase with zidovudine/lamivudine/abacavir plus tenofovir in HIV-1-infected patients with multidrug-resistant virus: a multicentre pilot study","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [53252628]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loswp.appleClientId = 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Hertogs</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Antimicrobial Chemotherapy, 2001</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors","attachmentId":46364576,"attachmentType":"pdf","work_url":"https://www.academia.edu/26017973/Distribution_of_K103N_and_or_Y181C_HIV_1_mutations_by_exposure_to_zidovudine_and_non_nucleoside_reverse_transcriptase_inhibitors","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/26017973/Distribution_of_K103N_and_or_Y181C_HIV_1_mutations_by_exposure_to_zidovudine_and_non_nucleoside_reverse_transcriptase_inhibitors"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="26071654" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/26071654/Zidovudine_treatment_results_in_the_selection_of_human_immunodeficiency_virus_type_1_variants_whose_genotypes_confer_increasing_levels_of_drug_resistance">Zidovudine treatment results in the selection of human immunodeficiency virus type 1 variants whose genotypes confer increasing levels of drug resistance</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="49957439" href="https://imperial.academia.edu/PaulKellam">Paul Kellam</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of General Virology, 1994</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Zidovudine treatment results in the selection of human immunodeficiency virus type 1 variants whose genotypes confer increasing levels of drug resistance","attachmentId":46419609,"attachmentType":"pdf","work_url":"https://www.academia.edu/26071654/Zidovudine_treatment_results_in_the_selection_of_human_immunodeficiency_virus_type_1_variants_whose_genotypes_confer_increasing_levels_of_drug_resistance","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/26071654/Zidovudine_treatment_results_in_the_selection_of_human_immunodeficiency_virus_type_1_variants_whose_genotypes_confer_increasing_levels_of_drug_resistance"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="75396433" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/75396433/Rapid_accumulation_of_HIV_1_thymidine_analogue_mutations_and_phenotypic_impact_following_prolonged_viral_failure_on_zidovudine_based_first_line_ART_in_sub_Saharan_Africa">Rapid accumulation of HIV-1 thymidine analogue mutations and phenotypic impact following prolonged viral failure on zidovudine-based first-line ART in sub-Saharan Africa</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="189989788" href="https://independent.academia.edu/hopeoctavia">hope octavia</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The Journal of antimicrobial chemotherapy, 2017</p><p class="ds-related-work--abstract ds2-5-body-sm">Lack of viral load monitoring of ART is known to be associated with slower switch from a failing regimen and thereby higher prevalence of MDR HIV-1. Many countries have continued to use thymidine analogue drugs despite recommendations to use tenofovir in combination with a cytosine analogue and NNRTI as first-line ART. The effect of accumulated thymidine analogue mutations (TAMs) on phenotypic resistance over time has been poorly characterized in the African setting. A retrospective analysis of individuals with ongoing viral failure between weeks 48 and 96 in the NORA (Nevirapine OR Abacavir) study was conducted. We analysed 36 genotype pairs from weeks 48 and 96 of first-line ART (14 treated with zidovudine/lamivudine/nevirapine and 22 treated with zidovudine/lamivudine/abacavir). Phenotypic drug resistance was assessed using the Antivirogram assay (v. 2.5.01, Janssen Diagnostics). At 96 weeks, extensive TAMs (≥3 mutations) were present in 50% and 73% of nevirapine- and abacavir-tr...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Rapid accumulation of HIV-1 thymidine analogue mutations and phenotypic impact following prolonged viral failure on zidovudine-based first-line ART in sub-Saharan Africa","attachmentId":83181615,"attachmentType":"pdf","work_url":"https://www.academia.edu/75396433/Rapid_accumulation_of_HIV_1_thymidine_analogue_mutations_and_phenotypic_impact_following_prolonged_viral_failure_on_zidovudine_based_first_line_ART_in_sub_Saharan_Africa","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/75396433/Rapid_accumulation_of_HIV_1_thymidine_analogue_mutations_and_phenotypic_impact_following_prolonged_viral_failure_on_zidovudine_based_first_line_ART_in_sub_Saharan_Africa"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="52558494" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/52558494/The_L74V_Mutation_in_Human_Immunodeficiency_Virus_Type_1_Reverse_Transcriptase_Counteracts_Enhanced_Excision_of_Zidovudine_Monophosphate_Associated_with_Thymidine_Analog_Resistance_Mutations">The L74V Mutation in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Counteracts Enhanced Excision of Zidovudine Monophosphate Associated with Thymidine Analog Resistance Mutations</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="183985823" href="https://independent.academia.edu/LuisReyesMiranda">Luis Reyes Miranda</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Antimicrobial Agents and Chemotherapy, 2005</p><p class="ds-related-work--abstract ds2-5-body-sm">Thymidine analog mutations (TAMs) in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) confer resistance to zidovudine (AZT) by increasing the rate of ATP-dependent phosphorolysis of the terminal nucleotide monophosphate (primer unblocking). By contrast, the L74V mutation, which confers resistance to didanosine, sensitizes HIV-1 to AZT and partially restores AZT susceptibility when present together with one or more TAMs. To compare rates of primer unblocking in RTs carrying different clusters of TAMs and to explore the biochemical mechanism by which L74V affects AZT susceptibility, ATP-mediated rescue of AZT-blocked DNA synthesis was assayed using a series of purified recombinant RTs. Rates of primer unblocking were higher in the 67N/70R/219Q RT than in the 41L/210W/215Y enzyme and were similar to rates observed with an RT carrying six TAMs (41L/67N/70R/210W/215Y/219Q). The presence of 74V in an otherwise wild-type RT reduced the rate of primer unblocking to a d...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The L74V Mutation in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Counteracts Enhanced Excision of Zidovudine Monophosphate Associated with Thymidine Analog Resistance Mutations","attachmentId":69768173,"attachmentType":"pdf","work_url":"https://www.academia.edu/52558494/The_L74V_Mutation_in_Human_Immunodeficiency_Virus_Type_1_Reverse_Transcriptase_Counteracts_Enhanced_Excision_of_Zidovudine_Monophosphate_Associated_with_Thymidine_Analog_Resistance_Mutations","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/52558494/The_L74V_Mutation_in_Human_Immunodeficiency_Virus_Type_1_Reverse_Transcriptase_Counteracts_Enhanced_Excision_of_Zidovudine_Monophosphate_Associated_with_Thymidine_Analog_Resistance_Mutations"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="18792808" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/18792808/The_prevalence_of_reduced_zidovudine_susceptibility_in_zidovudine_naive_antiretroviral_experienced_HIV_1_infected_patients">The prevalence of reduced zidovudine susceptibility in zidovudine-naive, antiretroviral-experienced HIV-1-infected patients</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38756884" href="https://imperial.academia.edu/SundhiyaMandalia">Sundhiya Mandalia</a></div><p class="ds-related-work--metadata ds2-5-body-xs">HIV Medicine, 2003</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The prevalence of reduced zidovudine susceptibility in zidovudine-naive, antiretroviral-experienced HIV-1-infected patients","attachmentId":40257886,"attachmentType":"pdf","work_url":"https://www.academia.edu/18792808/The_prevalence_of_reduced_zidovudine_susceptibility_in_zidovudine_naive_antiretroviral_experienced_HIV_1_infected_patients","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/18792808/The_prevalence_of_reduced_zidovudine_susceptibility_in_zidovudine_naive_antiretroviral_experienced_HIV_1_infected_patients"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="26071665" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/26071665/Fifth_mutation_in_human_immunodeficiency_virus_type_1_reverse_transcriptase_contributes_to_the_development_of_high_level_resistance_to_zidovudine">Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="49957439" href="https://imperial.academia.edu/PaulKellam">Paul Kellam</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Proceedings of the National Academy of Sciences, 1992</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine","attachmentId":46419592,"attachmentType":"pdf","work_url":"https://www.academia.edu/26071665/Fifth_mutation_in_human_immunodeficiency_virus_type_1_reverse_transcriptase_contributes_to_the_development_of_high_level_resistance_to_zidovudine","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/26071665/Fifth_mutation_in_human_immunodeficiency_virus_type_1_reverse_transcriptase_contributes_to_the_development_of_high_level_resistance_to_zidovudine"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="12617253" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/12617253/Clinical_virological_and_biochemical_evidence_supporting_the_association_of_HIV_1_reverse_transcriptase_polymorphism_R284K_and_thymidine_analogue_resistance_mutations_M41L_L210W_and_T215Y_in_patients_failing_tenofovir_emtricitabine_therapy">Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31566262" href="https://independent.academia.edu/IViciana">I. 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You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="26071648" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/26071648/Effects_of_discontinuation_of_zidovudine_treatment_on_zidovudine_sensitivity_of_human_immunodeficiency_virus_type_1_isolates">Effects of discontinuation of zidovudine treatment on zidovudine sensitivity of human immunodeficiency virus type 1 isolates</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="49957439" href="https://imperial.academia.edu/PaulKellam">Paul Kellam</a></div><p 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ds2-5-body-xs">Antimicrobial agents and chemotherapy, 1998</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Coresistance to zidovudine and foscarnet is associated with multiple mutations in the human immunodeficiency virus type 1 reverse transcriptase","attachmentId":72445414,"attachmentType":"pdf","work_url":"https://www.academia.edu/57645630/Coresistance_to_zidovudine_and_foscarnet_is_associated_with_multiple_mutations_in_the_human_immunodeficiency_virus_type_1_reverse_transcriptase","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/57645630/Coresistance_to_zidovudine_and_foscarnet_is_associated_with_multiple_mutations_in_the_human_immunodeficiency_virus_type_1_reverse_transcriptase"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="4" data-entity-id="79434305" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/79434305/N348I_in_reverse_transcriptase_provides_a_genetic_pathway_for_HIV_1_to_select_thymidine_analogue_mutations_and_mutations_antagonistic_to_thymidine_analogue_mutations">N348I in reverse transcriptase provides a genetic pathway for HIV-1 to select thymidine analogue mutations and mutations antagonistic to thymidine analogue mutations</a><div 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href="https://www.academia.edu/58059795/Variations_in_Reverse_Transcriptase_and_RNase_H_Domain_Mutations_in_Human_Immunodeficiency_Virus_Type_1_Clinical_Isolates_Are_Associated_with_Divergent_Phenotypic_Resistance_to_Zidovudine"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="7" data-entity-id="78921459" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/78921459/Frequency_and_Treatment_Related_Predictors_of_Thymidine_Analogue_Mutation_Patterns_in_HIV_1_Isolates_after_Unsuccessful_Antiretroviral_Therapy">Frequency and Treatment‐Related Predictors of Thymidine‐Analogue Mutation Patterns in HIV‐1 Isolates after Unsuccessful Antiretroviral Therapy</a><div 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translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/78921459/Frequency_and_Treatment_Related_Predictors_of_Thymidine_Analogue_Mutation_Patterns_in_HIV_1_Isolates_after_Unsuccessful_Antiretroviral_Therapy"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="8" data-entity-id="21050311" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/21050311/Long_term_foscarnet_therapy_remodels_thymidine_analogue_mutations_and_alters_resistance_to_zidovudine_and_lamivudine_in_HIV_1">Long-term foscarnet therapy remodels thymidine 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