Although antiretroviral therapy (ART) effectively suppresses HIV replication, the latent reservoir remains the barrier to HIV eradication. It remains unknown whether long-term ART impacts levels of inducible replication-competent provirus. To address this knowledge gap, we assessed the proviral reservoir in HIV-1 perinatally infected adolescents having received ART for >13 years. We recruited 15 vertically infected adolescents living with HIV in Botswana. Historical viral load, CD4⁺ T cell count, and treatment data were retrieved from their outpatient medical records. Inducible replication-competent proviruses from cryopreserved peripheral blood mononuclear cells were quantified using a TZM-bl based assay (TZA). Total proviral DNA copies were quantified using droplet digital PCR. The mean age of study participants was 16 years (standard deviation = 0.7) and median CD4⁺ T cell count at enrollment was 784 [interquartile range (IQR) = 728.8–1,288] cells/mm³. Median age at ART initiation was 8 (IQR = 6–12) months. Fourteen (93%) participants had HIV-1 RNA <400 copies/mL at the time of enrollment in the study. A median of 19 (IQR = 18–27) HIV-1 RNA measurements were available per participant. Six (40%) participants displayed viral suppression at all clinic visits since initiating ART, whereas the remaining 9 (60%) had one or more clinic visits with detectable HIV-1 RNA. The median inducible replication-competent provirus count was 7.4 infectious units per million cells (IQR = 6.7–19.2), and did not differ significantly by either complete or incomplete viral suppression (7.2 vs. 7.4, p = .86), or by age at ART initiation (7.4 if <12 months, 11.2 if >12 months, p = .85). The median total HIV DNA count was 129.1 copies per million cells (IQR = 18.9–212.3). Our data suggest that long-term ART initiated within the 1st year in perinatally infected infants did not eliminate proviral DNA or inducible replication-competent proviruses.

中文翻译：

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尽管对博茨瓦纳围产期感染的青少年进行了长期抗逆转录病毒治疗，但仍能检测到具有诱导复制能力的 HIV-1C 前病毒。

尽管抗逆转录病毒疗法 (ART) 有效地抑制了 HIV 复制，但潜在的水库仍然是根除 HIV 的障碍。尚不清楚长期 ART 是否会影响可诱导复制的前病毒的水平。为了解决这一知识差距，我们评估了接受 ART 超过 13 年的 HIV-1 围产期感染青少年的前病毒库。我们在博茨瓦纳招募了 15 名垂直感染 HIV 的青少年。历史病毒载量，CD4 ⁺从他们的门诊病历中检索 T 细胞计数和治疗数据。使用基于 TZM-bl 的测定 (TZA) 量化来自冷冻保存的外周血单核细胞的可诱导复制原病毒。使用液滴数字 PCR 对总前病毒 DNA 拷贝进行定量。研究参与者的平均年龄为 16 岁（标准差 = 0.7），入组时 CD4 ⁺ T 细胞计数中位数为 784 [四分位距 (IQR) = 728.8–1,288] 个细胞/mm ³. ART 开始时的中位年龄为 8 (IQR = 6-12) 个月。14 名 (93%) 参与者在参加研究时 HIV-1 RNA <400 拷贝/毫升。每个参与者可获得 19 (IQR = 18–27) HIV-1 RNA 测量值的中位数。自开始 ART 以来，六名 (40%) 参与者在所有诊所就诊中都表现出病毒抑制，而其余 9 名 (60%) 进行了一次或多次诊所就诊，可检测到 HIV-1 RNA。具有诱导复制能力的原病毒计数中位数为每百万细胞 7.4 个感染单位（IQR = 6.7-19.2），并且在完全或不完全病毒抑制（7.2 vs. 7.4，p  = .86）或年龄方面没有显着差异在 ART 开始时（如果 <12 个月为 7.4，如果 >12 个月为 11.2，p = .85）。HIV DNA 总数的中位数为每百万细胞 129.1 个拷贝（IQR = 18.9–212.3）。我们的数据表明，围产期感染的婴儿在第 1 年内开始的长期 ART 并没有消除前病毒 DNA 或可诱导复制的前病毒。