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Basic Characteristics of Mutations
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Mutation Site
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E138K |
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Mutation Site Sentence
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Surveillance drug resistance mutations (SDRM) to INSTI class was detected in three cases (1.6%; 95% CI: 0.5%-5%), two E138K and one R263K, with 7.8% (95% CI: 5%-13%) with resistance mutations (major or accessory). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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IN |
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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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INSTI |
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Location
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Brazil |
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Literature Information
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PMID
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39041595
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Title
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Transmitted Antiretroviral Drug Resistance to Integrase Strand Transfer Inhibitors Class in Sao Paulo Metropolitan Area, Brazil
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Author
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Matsuda EM,da Silva Santos JH,Ahagon CM,Lopez-Lopes GIS,Brigido LFM
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Journal
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AIDS research and human retroviruses
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Journal Info
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2024 Dec;40(12):713-717
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Abstract
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A newer integrase strand transfer inhibitor (INSTI) cabotegravir was recently approved for both therapy and prophylaxis and can play an essential role in the fight against AIDS. It shares similar resistance profile to dolutegravir, the cornerstone of Brazilian antiretroviral (ARV) treatment, with about 600 thousand people living with HIV in Brazil currently on regimens that contain this INSTI. Health services in the Sao Paulo metropolitan area are responsible for a large proportion of ARV dispensation in the country. Estimating transmitted drug resistance mutation (TDRM) in the area before cabotegravir introduction may provide a useful baseline information. Partial HIV-1 pol gene was sequenced (Sanger) from 192 newly diagnosed individuals from Sao Paulo and nearby cities (2020 to March 2023) at integrase, with 85 also at protease/reverse transcriptase regions. Retrotranscribed plasma RNA, amplified with nested PCR, was edited (Recall or Sequencher) and analyzed at Rega and Stanford db. Surveillance drug resistance mutations (SDRM) to INSTI class was detected in three cases (1.6%; 95% CI: 0.5%-5%), two E138K and one R263K, with 7.8% (95% CI: 5%-13%) with resistance mutations (major or accessory). SDRM for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and PI classes were identified in 7 (8.2% CI: 95% 4%-16%) cases. Subtype B predominated (69%), followed by subtype C (16%), now the second most prevalent infection in this area. Among 131 patients treated for over 6 months, 92% were virally suppressed below 200 copies/mL, with low TCD4 counts independently associated to failure. SDRM to INSTI class is rare in the area. Intermediate rates of transmitted resistance to other ARV classes are comparable to previous estimates. Viral suppression rates may depend on TCD4 counts, another negative impact of late diagnosis in care that deserves more attention.
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Sequence Data
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OR391537-OR391728
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