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Basic Characteristics of Mutations
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Mutation Site
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K70K |
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Mutation Site Sentence
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Figure 3 Diagrams depicting the HIV-1 ribonucleic acid (RNA) trajectories in two participants who developed dolutegravir resistance. Participant (a) developed intermediate dolutegravir resistance (Stanford score: 50), detected at week 96; clinical information: female, 40 years old, baseline HIV-1 RNA 4.30 log10 copies/mL, baseline CD4 lymphocyte count: 256 cells/μL. Participant (b) developed high-level dolutegravir resistance (Stanford score: 70), detected at week 146; clinical information: Male, 39 years old, baseline HIV-1 RNA 4.30 log10 copies/mL, baseline CD4 lymphocyte count: 175 cells/μL. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Synonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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NRTI |
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Location
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South Africa |
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Literature Information
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PMID
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40356938
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Title
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Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ART
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Author
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van Heerden JK,Zhao Y,Keene CM,Griesel R,Omar Z,Goliath R,Delaney K,van Zyl G,Maartens G,Meintjes G
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Journal
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Southern African journal of HIV medicine
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Journal Info
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2025 Apr 30;26(1):1677
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Abstract
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BACKGROUND: Dolutegravir in second-line antiretroviral therapy (ART) is more effective with recycled tenofovir than switching to zidovudine. However, dolutegravir resistance is more frequent in second-line compared to first-line ART. OBJECTIVES: We report long-term virologic outcomes from a clinical trial. METHOD: AntiRetroviral Therapy In Second-line: investigating Tenofovir-lamivudine-dolutegravir (ARTIST) was a randomised, double-blind, phase II clinical trial. Eligible participants had two consecutive HIV-1 RNA >/= 1000 copies/mL on first-line ART, mostly tenofovir-emtricitabine-efavirenz. Participants were switched to tenofovir-lamivudine-dolutegravir (TLD) with lead-in 50 mg dolutegravir twice daily in stage one (n = 62), and randomised to TLD with additional lead-in 50 mg dolutegravir or placebo for the first 14 days in stage two (n = 130). We present results up to 158 weeks, combining stages one and two. RESULTS: We enrolled 192 participants: 127/176 (72%) had resistance (Stanford score >/= 15) to both tenofovir and lamivudine. At week 48, 151/186 (81%; 95% confidence interval [CI] 75%, 87%) had HIV-1 RNA < 50 copies/mL. Of 127 participants with follow-up through week 158, 78% (95% CI 70%, 85%) maintained HIV-1 RNA < 50 copies/mL, 11% had HIV-1 RNA 50-999 copies/mL, and 11% had HIV-1 RNA >/= 1000 copies/mL. Twenty-nine participants met criteria for resistance testing: one developed intermediate-level dolutegravir resistance (G118R mutation) at week 96, and one had high-level dolutegravir resistance (E138K, G118R, G163R, T66A mutations) detected at week 146. CONCLUSION: Among adults switching to TLD with detectable HIV-1 RNA and substantial tenofovir and lamivudine resistance, a high proportion maintained virologic suppression up to 158 weeks. Emergent dolutegravir resistance occurred in ~1% of participants after 2-3 years on second-line TLD.
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Sequence Data
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-
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