Department of Global Health, University of Washington, Seattle, WA, USA; School of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Human Sciences Research Council, Sweetwaters, KwaZulu-Natal, South Africa.
Lancet HIV. 2016 May;3(5):e212-20. doi: 10.1016/S2352-3018(16)00020-5. Epub 2016 Mar 10.
BACKGROUND: Male circumcision decreases HIV acquisition by 60%, and antiretroviral therapy (ART) almost eliminates HIV transmission from HIV-positive people who are virally suppressed; however, coverage of these interventions has lagged behind targets. We aimed to assess whether community-based HIV testing with counsellor support and point-of-care CD4 cell count testing would increase uptake of ART and male circumcision. METHODS: We did this multisite, open-label, randomised controlled trial in six research-naive communities in rural South Africa and Uganda. Eligible HIV-positive participants (aged ≥16 years) were randomly assigned (1:1:1) in a factorial design to receive lay counsellor clinic linkage facilitation, lay counsellor follow-up home visits, or standard-of-care clinic referral, and then (1:1) either point-of-care CD4 cell count testing or referral for CD4 testing. HIV-negative uncircumcised men (aged 16-49 years) who could receive secure mobile phone text messages were randomly assigned (1:1:1) to receive text message reminders, lay counsellor visits, or standard clinic referral. The study biostatistician generated the randomisation schedule via a computer-generated random number program with varying block sizes (multiples of six or three) stratified by country. Primary outcomes for HIV-positive people were obtaining a CD4 cell count, linkage to an HIV clinic, ART initiation, and viral suppression at 9 months, and for HIV-negative uncircumcised men were visiting a circumcision facility and uptake of male circumcision at 3 months. We assessed social harms as a safety outcome throughout the study. We did the primary analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02038582. FINDINGS: Between June 6, 2013, and March 11, 2015, 15 332 participants were tested. 2339 (15%) participants tested HIV positive, of whom 1325 (57%) were randomly assigned to receive lay counsellor clinic linkage facilitation (n=437), lay counsellor follow-up home visits (n=449), or standard clinic referral (n=439), and then point-of-care CD4 cell testing (n=206, n=220, and n=213, respectively) or referral for CD4 testing (n=231, n=229, and n=226, respectively). 12 993 (85%) participants tested HIV negative, of whom 750 (6%) uncircumcised men were randomly assigned to receive clinic referral (n=230), text message reminders (n=288), or lay counsellor follow-up visits (n=232). 1218 (93%) of 1303 HIV-positive participants were linked to care, but only 488 (37%) participants initiated ART. Overall, 635 (50%) of 1272 HIV-positive individuals achieved viral suppression at 9 months: 219 (52%) of 419 participants in the clinic facilitation group, 202 (47%) of 431 participants in the lay counsellor follow-up group, and 214 (51%) of 422 participants in the clinic referral group, with no significant differences between groups (p=0·668 for clinic facilitation and p=0·273 for lay counsellor follow-up vs clinic referral). 523 (72%) of 734 HIV-negative men visited a circumcision facility, with no difference between groups. 62 (28%) of 224 men were circumcised in the male circumcision clinic referral group compared with 137 (48%) of 284 men in the text message reminder group (relative risk 1·72, 95% CI 1·36-2·17; p<0·0001) and 106 (47%) of 226 men in the lay counsellor follow-up group (1·67, 1·29-2·14; p=0·0001). No cases of study-related social harm were reported, including probing about partnership separation, unintended disclosure, gender-based violence, and stigma. INTERPRETATION: All the community-based strategies achieved high rates of linkage of HIV-positive people to HIV clinics, roughly a third of whom initiated ART, and of those more than 80% were virally suppressed at 9 months. Uptake of male circumcision was almost two-times higher in men who received text message reminders or lay counsellor visits than in those who received standard-of-care clinic referral. Clinic barriers to ART initiation should be addressed in future strategies to increase the proportion of HIV-positive people accessing treatment and achieving viral suppression. FUNDING: National Institute of Allergy and Infectious Diseases, National Institutes of Health.
背景:男性包皮环切术可使 HIV 感染率降低 60%,而抗逆转录病毒疗法(ART)几乎可以消除 HIV 阳性且病毒得到抑制的人将 HIV 传播给他人的风险;然而,这些干预措施的覆盖率落后于目标。我们旨在评估基于社区的 HIV 检测加上辅导员支持和即时 CD4 细胞计数检测是否会增加接受 ART 和男性包皮环切术的人数。
方法:我们在南非和乌干达的 6 个研究社区进行了这项多中心、开放性、随机对照试验。符合条件的 HIV 阳性参与者(年龄≥16 岁)按 1:1:1 的比例随机分配(析因设计),接受初级保健医生门诊就诊协助、初级保健医生家访或标准护理门诊转诊,并进一步(1:1)接受即时 CD4 细胞计数检测或 CD4 检测转诊。未接受包皮环切术且 HIV 阴性的 16-49 岁男性,如果可以接收安全的手机短信,将按 1:1:1 的比例随机分配接受短信提醒、初级保健医生家访或标准诊所转诊。研究生物统计学家使用计算机生成的随机数程序生成随机分组方案,该程序的分组大小(六的倍数或三的倍数)因国家而异。HIV 阳性参与者的主要结局是获得 CD4 细胞计数、与 HIV 诊所建立联系、开始接受 ART 治疗以及在 9 个月时病毒得到抑制,而 HIV 阴性未接受包皮环切术的男性的主要结局是前往包皮环切机构和接受男性包皮环切术。我们在整个研究过程中评估了社会危害作为安全性结局。我们通过意向治疗进行主要分析。本试验在 ClinicalTrials.gov 注册,编号为 NCT02038582。
发现:2013 年 6 月 6 日至 2015 年 3 月 11 日期间,共有 15332 名参与者接受了检测。2339 名(15%)参与者 HIV 检测呈阳性,其中 1325 名(57%)参与者被随机分配接受初级保健医生门诊就诊协助(n=437)、初级保健医生家访(n=449)或标准护理门诊转诊(n=439),然后接受即时 CD4 细胞计数检测(n=206、n=220 和 n=213)或 CD4 检测转诊(n=231、n=229 和 n=226)。12993 名(85%)参与者 HIV 检测呈阴性,其中 750 名(6%)未接受包皮环切术的男性被随机分配接受门诊转诊(n=230)、短信提醒(n=288)或初级保健医生家访(n=232)。1303 名 HIV 阳性参与者中的 1218 名(93%)与护理建立了联系,但只有 488 名(37%)参与者开始接受 ART 治疗。总的来说,在 9 个月时,635 名(50%)HIV 阳性个体实现了病毒抑制:219 名(52%)在门诊协助组,202 名(47%)在初级保健医生家访组,214 名(51%)在门诊转诊组,各组之间无显著差异(门诊协助与门诊转诊相比,p=0.668;初级保健医生家访与门诊转诊相比,p=0.273)。734 名 HIV 阴性男性中有 523 名(72%)参观了包皮环切机构,各组之间没有差异。在男性包皮环切术转诊组中,62 名(28%)男性接受了包皮环切术,而在短信提醒组中,284 名(48%)男性接受了包皮环切术(相对风险 1.72,95%CI 1.36-2.17;p<0.0001),在初级保健医生家访组中,106 名(47%)226 名男性接受了包皮环切术(1.67,1.29-2.14;p=0.0001)。没有报告与研究相关的社会危害事件,包括探查伴侣分离、意外披露、性别暴力和耻辱感。
解释:所有基于社区的策略都实现了 HIV 阳性人群与 HIV 诊所的高连接率,其中约三分之一的人开始接受 ART 治疗,在 9 个月时,超过 80%的人病毒得到抑制。在接受短信提醒或初级保健医生家访的男性中,接受包皮环切术的比例几乎是接受标准护理门诊转诊的男性的两倍。在未来的策略中,应该解决门诊就诊的障碍,以增加接受治疗和实现病毒抑制的 HIV 阳性人群的比例。
经费来源:美国国立过敏和传染病研究所,美国国立卫生研究院。
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