Africa Health Research Institute, Durban, KwaZulu-Natal, South Africa; Research Department of Infection and Population Health, University College London, London, UK; Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
University of Bordeaux, ISPED, INSERM, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France.
Lancet HIV. 2018 Mar;5(3):e116-e125. doi: 10.1016/S2352-3018(17)30205-9. Epub 2017 Nov 30.
Universal antiretroviral therapy (ART), as per the 2015 WHO recommendations, might reduce population HIV incidence. We investigated the effect of universal test and treat on HIV acquisition at population level in a high prevalence rural region of South Africa.
We did a phase 4, open-label, cluster randomised trial of 22 communities in rural KwaZulu-Natal, South Africa. We included individuals residing in the communities who were aged 16 years or older. The clusters were composed of aggregated local areas (neighbourhoods) that had been identified in a previous study in the Hlabisa subdistrict. The study statisticians randomly assigned clusters (1:1) with MapInfo Pro (version 11.0) to either the control or intervention communities, stratified on the basis of antenatal HIV prevalence. We offered residents repeated rapid HIV testing during home-based visits every 6 months for about 4 years in four clusters, 3 years in six clusters, and 2 years in 12 clusters (58 cluster-years) and referred HIV-positive participants to trial clinics for ART (fixed-dose combination of tenofovir, emtricitabine, and efavirenz) regardless of CD4 cell count (intervention) or according to national guidelines (initially ≤350 cells per μL and <500 cells per μL from January, 2015; control). Participants and investigators were not masked to treatment allocation. We used dried blood spots once every 6 months provided by participants who were HIV negative at baseline to estimate the primary outcome of HIV incidence with cluster-adjusted Poisson generalised estimated equations in the intention-to-treat population after 58 cluster-years of follow-up. This study is registered with ClinicalTrials.gov, number NCT01509508, and the South African National Clinical Trials Register, number DOH-27-0512-3974.
Between March 9, 2012, and June 30, 2016, we contacted 26 518 (93%) of 28 419 eligible individuals. Of 17 808 (67%) individuals with a first negative dried blood spot test, 14 223 (80%) had subsequent dried blood spot tests, of whom 503 seroconverted after follow-up of 22 891 person-years. Estimated HIV incidence was 2·11 per 100 person-years (95% CI 1·84-2·39) in the intervention group and 2·27 per 100 person-years (2·00-2·54) in the control group (adjusted hazard ratio 1·01, 95% CI 0·87-1·17; p=0·89). We documented one case of suicidal attempt in a woman following HIV seroconversion. 128 patients on ART had 189 life-threatening or grade 4 clinical events: 69 (4%) of 1652 in the control group and 59 (4%) of 1367 in the intervention group (p=0·83).
The absence of a lowering of HIV incidence in universal test and treat clusters most likely resulted from poor linkage to care. Policy change to HIV universal test and treat without innovation to improve health access is unlikely to reduce HIV incidence.
ANRS, GiZ, and 3ie.
根据 2015 年世卫组织的建议，普遍开展抗逆转录病毒疗法（ART）可能会降低人群中的 HIV 发病率。我们在南非夸祖鲁-纳塔尔省一个高 HIV 流行的农村地区，调查了普遍检测和治疗对人群 HIV 感染率的影响。
我们在南非夸祖鲁-纳塔尔省农村的 Hlabisa 分区进行了一项 4 期、开放标签、集群随机试验，纳入了居住在社区中年龄在 16 岁及以上的个体。集群由先前在 Hlabisa 分区的一项研究中确定的聚合当地区域（社区）组成。研究统计人员使用 MapInfo Pro（版本 11.0）随机将集群（1:1）分配到对照组或干预组，分配基于产前 HIV 流行率。我们在四年内（四个集群每 6 个月进行一次、六个集群每 3 个月进行一次、十二个集群每 2 个月进行一次）在四个集群中为居民提供了多次家庭访问的快速 HIV 检测，在近四年（58 个集群年）中对 HIV 阳性参与者进行了抗逆转录病毒治疗（替诺福韦、恩曲他滨和依非韦伦的固定剂量组合），无论 CD4 细胞计数如何（干预组）或根据国家指南（从 2015 年 1 月起，初始值 ≤350 个细胞/μL 和＜500 个细胞/μL；对照组）。参与者和研究人员对治疗分配没有被蒙蔽。我们使用基线时 HIV 阴性的参与者提供的每 6 个月一次的干血斑，在经过 58 个集群年后，对符合意向治疗人群进行了 HIV 发病率的主要结局评估，采用集群调整的泊松广义估计方程。这项研究在 ClinicalTrials.gov 注册，编号为 NCT01509508，在南非国家临床试验注册处注册，编号为 DOH-27-0512-3974。
在 2012 年 3 月 9 日至 2016 年 6 月 30 日期间，我们联系了 26518 名（93%）符合条件的个体中的 17808 名（67%）首次进行了阴性干血斑检测的个体中，有 14223 名（80%）进行了后续干血斑检测，其中 503 名在随访 22891 人年之后发生了血清转换。干预组 HIV 发病率为 2.11/100 人年（95%CI 1.84-2.39），对照组为 2.27/100 人年（2.00-2.54）（调整后的危险比为 1.01，95%CI 0.87-1.17；p=0.89）。我们记录了一名女性在 HIV 血清转换后企图自杀的病例。128 名接受抗逆转录病毒治疗的患者出现了 189 例危及生命或 4 级临床事件：对照组 69 例（4%），干预组 59 例（4%）（p=0.83）。
普遍检测和治疗集群中 HIV 发病率没有降低，这很可能是由于治疗关联性差所致。如果没有改善卫生服务获取途径的创新措施，而只是改变 HIV 普遍检测和治疗政策，不太可能降低 HIV 发病率。
法国国家艾滋病研究署、德国全球卫生合作基金会和 3ie。
