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High Levels of Acquired HIV Drug Resistance Following Virological Nonsuppression in HIV-Infected Women from a High-Risk Cohort in Uganda.
AIDS Research and Human Retroviruses ( IF 1.5 ) Pub Date : 2020-09-08 , DOI: 10.1089/aid.2019.0279
Farouk Segujja 1, 2, 3 , Jonah Omooja 1, 2, 3 , Sandra Lunkuse 1 , Maria Nanyonjo 1 , Stella E Nabirye 1 , Faridah Nassolo 1 , Daniel L Bugembe 1 , Nicholas Bbosa 1 , David P Kateete 2, 3 , William Ssenyonga 1 , Yunia Mayanja 1 , Rebecca N Nsubuga 1 , Janet Seeley 1, 4 , Pontiano Kaleebu 1, 5 , Deogratius Ssemwanga 1, 5
Affiliation  

HIV drug resistance (HIVDR) is of increasing health concern, especially among key populations. We investigated the prevalence of virological suppression (VS), prevalence and correlates of HIVDR in HIV-infected women, enrolled in a high-risk cohort. We enrolled 267 women initiated on first-line antiretroviral therapy (ART) between 2015 and 2018. Participants' plasma samples were analyzed for HIV RNA viral load (VL) and genotypic resistance testing was performed on those with VL nonsuppression (defined as VL ≥1,000 copies/mL). We used the Stanford HIVDR database-algorithm to assess HIVDR mutations and logistic regression to assess risk factors for VL nonsuppression and HIVDR. We observed an overall VS prevalence of 76.0% (203/267) and detected respective acquired drug resistance prevalence to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) of 81.3% [confidence interval (CI) 67.4–91.1] and 45.8% (CI 31.4–60.8) among the 48 successfully genotyped VL nonsuppressors. NNRTI mutations were observed in 81.3% (39/48) of the genotyped participants and 45.8% (22/48) had both NRTI and NNRTI mutations. The mutation K103N was detected in 62.5% (30/48) of participants, 41.7% (20/48) had M184V/I, 14.6% had K65R, and 12.5% (6/48) had thymidine analog mutations (TAMs). None of the analyzed potential risk factors, including age and duration on ART, was significantly correlated with VL nonsuppression or HIVDR. Although high levels of NNRTI mutations support the transition to dolutegravir, the presence of NRTI mutations, especially TAMs, may compromise dolutegravir-based regimens or other second-line ART options. The moderate VS prevalence and high HIVDR prevalence therefore call for timely ART switching and intensive adherence counseling.

中文翻译:

来自乌干达高危人群的 HIV 感染妇女在病毒学不抑制后获得高水平的 HIV 耐药性。

HIV 耐药性 (HIVDR) 日益引起人们的健康关注,尤其是在重点人群中。我们调查了纳入高风险队列的 HIV 感染女性的病毒学抑制 (VS) 流行率、HIVDR 流行率和相关性。我们招募了 267 名在 2015 年至 2018 年期间开始接受一线抗逆转录病毒治疗 (ART) 的女性。对参与者的血浆样本进行 HIV RNA 病毒载量 (VL) 分析,并对 VL 不抑制的患者(定义为 VL ≥ 1,000份/毫升)。我们使用斯坦福 HIVDR 数据库算法来评估 HIVDR 突变和逻辑回归以评估 VL 不抑制和 HIVDR 的风险因素。我们观察到总体 VS 患病率为 76。0% (203/267) 并检测到非核苷类逆转录酶抑制剂 (NNRTIs) 和核苷类逆转录酶抑制剂 (NRTIs) 的获得性耐药率分别为 81.3% [置信区间 (CI) 67.4–91.1] 和 45.8% (CI) 31.4-60.8)在 48 个成功基因分型的 VL 非抑制因子中。在 81.3% (39/48) 的基因分型参与者中观察到 NNRTI 突变,45.8% (22/48) 有 NRTI 和 NNRTI 突变。62.5% (30/48) 的参与者检测到 K103N 突变,41.7% (20/48) 有 M184V/I,14.6% 有 K65R,12.5% (6/48) 有胸苷类似物突变 (TAM)。分析的潜在风险因素(包括年龄和 ART 持续时间)均与 VL 不抑制或 HIVDR 显着相关。尽管高水平的 NNRTI 突变支持向多替拉韦过渡,NRTI 突变的存在,尤其是 TAM,可能会影响基于多替拉韦的治疗方案或其他二线 ART 选择。因此,中度 VS 患病率和高 HIVDR 患病率要求及时进行 ART 转换和强化依从性咨询。
更新日期:2020-09-11
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