Matsuda Elaine Monteiro, da Silva Santos Jaqueline Helena, Ahagon Cintia Mayumi, López-Lopes Giselle Ibete Silva, Brígido Luís Fernando de Macedo
Santo André Health Secretary, São Paulo, Brazil.
Virology Center, Adolfo Lutz Institute, São Paulo, Brazil.
AIDS Res Hum Retroviruses. 2024 Dec;40(12):713-717. doi: 10.1089/AID.2023.0127. Epub 2024 Aug 8.
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 São 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 gene was sequenced (Sanger) from 192 newly diagnosed individuals from São 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.
一种较新的整合酶链转移抑制剂（INSTI）卡博特韦最近被批准用于治疗和预防，在抗击艾滋病中可发挥重要作用。它与多替拉韦具有相似的耐药谱，多替拉韦是巴西抗逆转录病毒（ARV）治疗的基石，目前巴西约有60万人感染艾滋病毒并正在接受含有这种INSTI的治疗方案。圣保罗大都市区的卫生服务机构负责该国很大一部分抗逆转录病毒药物的分发。在引入卡博特韦之前估计该地区的传播性耐药突变（TDRM）可能会提供有用的基线信息。对来自圣保罗及周边城市（2020年至2023年3月）的192名新诊断个体的HIV-1基因部分序列（桑格测序法）进行整合酶测序，其中85人还对蛋白酶/逆转录酶区域进行了测序。用巢式PCR扩增逆转录血浆RNA，在雷加和斯坦福数据库进行编辑（召回或序列分析软件）和分析。在3例（1.6%；95%置信区间：0.5%-5%）中检测到对INSTI类的监测耐药突变（SDRM），2例E138K和1例R263K，7.8%（95%置信区间：5%-13%）有耐药突变（主要或次要）。在7例（8.2%；95%置信区间：4%-16%）中鉴定出核苷类逆转录酶抑制剂、非核苷类逆转录酶抑制剂和蛋白酶抑制剂类的SDRM。B亚型占主导（69%），其次是C亚型（16%），C亚型现在是该地区第二常见的感染类型。在131名接受治疗超过6个月的患者中，92%的患者病毒载量被抑制在200拷贝/毫升以下，低TCD4细胞计数与治疗失败独立相关。该地区对INSTI类的SDRM很少见。对其他抗逆转录病毒药物类别的传播性耐药中间率与先前的估计相当。病毒抑制率可能取决于TCD4细胞计数，这是晚期诊断在治疗中的另一个负面影响，值得更多关注。
