Martin Genevieve E, Gossez Morgane, Williams James P, Stöhr Wolfgang, Meyerowitz Jodi, Leitman Ellen M, Goulder Philip, Porter Kholoud, Fidler Sarah, Frater John
aNuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford bMRC Clinical Trials Unit at University College London, London cDepartment of Paediatrics, University of Oxford, Oxford, UK dHarvard Medical School, Boston, Massachusetts, USA eHIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa fResearch Department of Infection and Population Health, University College London gDivision of Medicine, Wright Fleming Institute, Imperial College, London hThe Oxford Martin School iOxford National Institute of Health Research Biomedical Research Centre, Oxford, UK.
AIDS. 2017 Feb 20;31(4):477-484. doi: 10.1097/QAD.0000000000001382.
OBJECTIVE(S): An HIV cure will impose aviraemia that is sustained following the withdrawal of antiretroviral therapy (ART). Understanding the efficacy of novel interventions aimed at curing HIV requires characterization of both natural viral control and the effect of ART on viral control after treatment interruption.
Analysis of transient viral control in recent seroconverters in the Short Pulse AntiRetroviral Therapy at Acute Seroconversion trial.
We compared untreated and treated HIV seroconverters (n = 292) and identified periods of control (plasma HIV RNA < 400 copies/ml for ≥16 weeks off therapy) in 7.9% of ART-naive participants, and in 12.0% overall. HIV DNA was measured by qPCR, and HIV-specific CD8 responses were measured by enzyme-linked immunosorbent spot assay (ELISpot). T-cell activation and exhaustion were measured by flow cytometry.
At baseline, future controllers had lower HIV DNA, lower plasma HIV RNA, higher CD4 : CD8 ratios (all P < 0.001) and higher CD4 cell counts (P < 0.05) than noncontrollers. Among controllers, the only difference between the untreated and those who received ART was higher baseline HIV RNA in the latter (P = 0.003), supporting an added ART effect.
Consideration of spontaneous remission in untreated individuals will be critical to avoid overestimating the effect size of new interventions used in HIV cure studies.
治愈艾滋病病毒（HIV）将实现抗逆转录病毒疗法（ART）停药后持续的病毒血症抑制。了解旨在治愈HIV的新型干预措施的疗效，需要对自然病毒控制以及治疗中断后ART对病毒控制的影响进行特征描述。
在急性血清转化期短脉冲抗逆转录病毒疗法试验中，对近期血清转化者的短暂病毒控制进行分析。
我们比较了未经治疗和接受过治疗的HIV血清转化者（n = 292），并在7.9%的未接受过ART治疗的参与者以及总体12.0%的参与者中确定了病毒控制期（血浆HIV RNA<400拷贝/ml且停药≥16周）。通过定量聚合酶链反应（qPCR）测量HIV DNA，通过酶联免疫斑点试验（ELISpot）测量HIV特异性CD8反应。通过流式细胞术测量T细胞活化和耗竭情况。
在基线时，未来的病毒控制者与非控制者相比，HIV DNA水平更低、血浆HIV RNA水平更低、CD4∶CD8比值更高（均P<0.001）以及CD4细胞计数更高（P<0.05）。在病毒控制者中，未治疗者与接受过ART治疗者之间的唯一差异是后者的基线HIV RNA更高（P = 0.003），这支持了ART的额外作用。
考虑未治疗个体的自发缓解情况对于避免高估HIV治愈研究中使用的新干预措施的效应大小至关重要。
