Allogeneic bone marrow transplant (alloBMT) with continuous antiretroviral therapy alone has not been shown to completely eradicate HIV, possibly due to HIV persistence in rare residual host cells or infection of donor cells. Within a trial of alloBMT in individuals with hematological malignancies and HIV (ClinicalTrials.gov, NCT01836068), we measured HIV reservoirs longitudinally using a quantitative viral outgrowth assay. We sequenced the reverse transcriptase region of pol for replication-competent virus and performed maximum-likelihood phylogenetic reconstruction. Replacement of host cells was measured using short-tandem repeats. In one participant who had ≥99.5% donor cell replacement, HIV reservoirs declined from 2.2 infectious units per million to undetectable levels at post-alloBMT time points except for week 64. Sequence analysis revealed dual infection pre-alloBMT. Replication-competent virus isolated at week 64 post-alloBMT was identical to a pre-alloBMT variant. This report provides proof-of-concept that minor replication-competent HIV variants can persist at low levels despite ≥99.5% donor cell engraftment post-alloBMT.

中文翻译：

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简短沟通：双重感染个体异基因骨髓移植后 HIV 的持续存在

同种异体骨髓移植 (alloBMT) 联合连续抗逆转录病毒疗法尚未显示可完全根除 HIV，这可能是由于 HIV 在稀有残留宿主细胞中持续存在或供体细胞感染所致。在血液恶性肿瘤和 HIV 患者的同种异体 BMT 试验中（ClinicalTrials.gov，NCT01836068），我们使用定量病毒生长测定纵向测量了 HIV 储库。我们对pol的逆转录酶区域进行了测序对于具有复制能力的病毒，并进行了最大似然系统发育重建。使用短串联重复测量宿主细胞的替换。在一名供体细胞置换率≥99.5% 的参与者中，除第 64 周外，在同种异体 BMT 后的时间点，HIV 病毒库从每百万 2.2 个感染单位下降到检测不到的水平。序列分析显示双重感染前同种异体 BMT。alloBMT 后第 64 周分离出的具有复制能力的病毒与 alloBMT 前变体相同。该报告提供了概念验证，即尽管 alloBMT 后 ≥99.5% 的供体细胞植入，但具有复制能力的次要 HIV 变体仍可以保持在低水平。