Barriers to sustainable virologic suppression (VS) of HIV-infected adolescents and young adults include drug resistance mutations (DRMs) and limited treatment options, which may impact the outcome of second-line antiretroviral therapy (ART). We sequenced plasma viral RNA from 74 adolescents and young adults (16–24 years) failing first-line ART at Newlands Clinic, Zimbabwe between October 2015 and December 2016. We evaluated first-line nucleoside reverse transcriptase inhibitor (NRTI) susceptibility scores to first- and second-line regimens. Boosted protease inhibitor (bPI)-based ART was provided and viral load (VL) monitored for ≥48 weeks. Fisher's exact test was used to evaluate factors associated with VS on second-line regimens, defined as VL <1,000 copies/mL (VS_1,000) or <50 copies/mL (VS₅₀). The 74 participants on first-line ART had a median [interquartile range (IQR)] age of 18 (16–21) years and 42 (57%) were female. The mean (±standard deviation) duration on ART was 5.5 (±3.06) years and the median (IQR) log₁₀ VL was 4.26 (3.78–4.83) copies/mL. After switching to a second-line PI regimen, 88% suppressed to <1,000 copies/mL and 76% to <50 copies/mL at ≥48 weeks. A new NRTI was associated with increased VS₅₀ (p = .031). These 74 adolescents and young adults failing first-line ART demonstrated high levels (97%) of DRMs, despite enhanced adherence counseling. Switching to new NRTIs in second-line improved VS. With the widespread adoption of generic dolutegravir, lamivudine and tenofovir combinations in Africa, genotyping to determine NRTI susceptibility, may be warranted.

中文翻译：

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一线抗逆转录病毒疗法病毒学失败的青少年和年轻人的耐药性以及对二线治疗的反应。

艾滋病毒感染的青少年和年轻人的持续病毒抑制（VS）的障碍包括耐药性突变（DRM）和有限的治疗选择，这可能会影响二线抗逆转录病毒疗法（ART）的结果。我们对2015年10月至2016年12月在津巴布韦纽兰兹诊所一线抗病毒治疗失败的74名青少年和16岁至24岁青少年血浆病毒RNA进行了测序。 -和二线疗法。提供了基于增强的蛋白酶抑制剂（bPI）的抗逆转录病毒治疗，并监测了病毒载量（VL）≥48周。Fisher精确测试用于评估第二线方案中与VS相关的因素，定义为VL <1,000拷贝/ mL（VS _1,000）或<50拷贝/ mL（VS ₅₀）。一线抗逆转录病毒治疗的74名参与者的中位[四分位间距（IQR）]年龄为18（16-21）岁，女性为42（57％）。ART的平均（±标准差）持续时间为5.5（±3.06）年，log（_10） VL的中位数为4.26（3.78–4.83）拷贝/ mL。改用二线PI方案后，≥48周时有88％抑制至<1,000拷贝/ mL，76％抑制至<50拷贝/ mL。新的NRTI与VS ₅₀（p = .031）。尽管依从性咨询得到了加强，但这些一线抗病毒治疗失败的74名青少年显示出高水平的DRM（97％）。在二线改进的VS中切换到新的NRTI。随着通用的多洛格韦，拉米夫定和替诺福韦的组合在非洲的广泛采用，可能需要进行基因分型以确定NRTI的易感性。