aBC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada bMbarara University of Science and Technology, Mbarara, Uganda cHarvard Medical School dHarvard School of Public Health eMassachusetts General Hospital, Boston, Massachusetts fOregon Health Sciences University, Portland, Oregon gUniversity of California, San Francisco, California, USA. *P. Richard Harrigan and Guinevere Q. Lee equally contributed to this article.
AIDS. 2017 Nov 13;31(17):2345-2354. doi: 10.1097/QAD.0000000000001619.
HIV-1 subtypes A1 and D cocirculate in a rural community in Mbarara, Uganda. This study examines HIV-1 intersubtype recombination in this community under a full-genome sequencing context. We aim to estimate prevalence, examine time trends, and test for clinical correlates and outcomes associated with intersubtype recombinants.
Near-full-genome HIV-1 Sanger sequence data were collected from plasma samples of 504 treatment-naïve individuals, who then received protease inhibitor or nonnucleoside reverse transcriptase inhibitor-containing regimens and were monitored for up to 7.5 years. Subtypes were inferred by Los Alamos Recombinant Identification Program (RIP) 3.0 and compared with Sanger/REGA and MiSeq/RIP. 'Nonrecombinants' and 'recombinants' infections were compared in terms of pretherapy viral load, CD4 cell count, posttherapy time to virologic suppression, virologic rebound, first CD4 rise above baseline and sustained CD4 recovery.
Prevalence of intersubtype recombinants varied depending on the genomic region examined: gag (15%), prrt (11%), int (8%), vif (10%), vpr (2%), vpu (9%), GP120 (8%), GP41 (18%), and nef (4%). Of the 200 patients with near-full-genome data, prevalence of intersubtype recombination was 46%; the most frequently observed recombinant was A1-D (25%). Sanger/REGA and MiSeq/RIP yielded generally consistent results. Phylogenetic tree revealed most recombinants did not share common ancestors. No temporal trend was observed (all P > 0.1). Subsequent subtype switches were detected in 27 of 143 (19%) study participants with follow-up sequences. Nonrecombinant versus recombinants infections were not significantly different in any pre nor posttherapy clinical correlates examined (all P > 0.2).
Intersubtype recombination was highly prevalent (46%) in Uganda if the entire HIV genome was considered, but was neither associated with clinical correlates nor therapy outcomes.
HIV-1 亚型 A1 和 D 在乌干达姆巴拉拉的一个农村社区中共同流行。本研究在全基因组测序背景下，研究该社区中 HIV-1 亚型间重组的情况。我们旨在评估流行率，考察时间趋势，并检验与亚型间重组体相关的临床关联和结果。
从 504 名未接受治疗的个体的血浆样本中收集了近乎完整的 HIV-1 全长 Sanger 序列数据，然后这些个体接受了包含蛋白酶抑制剂或非核苷类逆转录酶抑制剂的治疗方案，并监测了长达 7.5 年的时间。通过 Los Alamos 重组识别程序（RIP）3.0 推断亚型，并与 Sanger/REGA 和 MiSeq/RIP 进行比较。在治疗前病毒载量、CD4 细胞计数、治疗后病毒学抑制时间、病毒学反弹、首次 CD4 升高超过基线和持续 CD4 恢复方面，对“非重组体”和“重组体”感染进行了比较。
根据所检查的基因组区域，亚型间重组的流行率有所不同：gag（15%）、prrt（11%）、int（8%）、vif（10%）、vpr（2%）、vpu（9%）、GP120（8%）、GP41（18%）和 nef（4%）。在 200 名具有近乎完整基因组数据的患者中，亚型间重组的流行率为 46%；最常见的重组是 A1-D（25%）。Sanger/REGA 和 MiSeq/RIP 产生的结果通常一致。系统发育树表明，大多数重组体没有共同的祖先。没有观察到时间趋势（所有 P > 0.1）。在具有随访序列的 143 名研究参与者中，检测到 27 名发生了后续的亚型转换。在任何治疗前或治疗后的临床相关性方面，非重组体与重组体感染均无显著差异（所有 P > 0.2）。
如果考虑整个 HIV 基因组，在乌干达，亚型间重组非常普遍（46%），但与临床相关性或治疗结果无关。
