Institut de Recherche pour le Développement (IRD), University Montpellier 1, UMI 233, Montpellier, France.
Lancet Infect Dis. 2011 Nov;11(11):825-33. doi: 10.1016/S1473-3099(11)70168-2. Epub 2011 Aug 8.
Scaling up of antiretroviral therapy in low-resource countries is done on the basis of decentralised, integrated HIV care in rural facilities; however, laboratory monitoring is generally unavailable. We aimed to assess the effectiveness and safety of clinical monitoring alone (CLIN) in terms of non-inferiority to laboratory and clinical monitoring (LAB).
We did a randomised, open-label, non-inferiority trial in nine rural district hospitals in Cameroon. Eligible participants were adults (≥18 years) infected with HIV-1 group M (WHO disease stage 3-4) who had not previously received antiretroviral therapy, and were followed-up for 2 years by health-care workers in routine activities. We randomly assigned participants (1:1) to CLIN or LAB (counts of HIV viral load and CD4 cell every 6 months) groups with a computer-generated list. The primary outcome was non-inferiority of CLIN to LAB in terms of increase in CD4 cell count with a non-inferiority margin of 25%. We did all analyses in participants who attended at least one follow-up visit. This trial is registered with ClinicalTrials.gov, number NCT00301561.
238 (93%) of 256 participants assigned to CLIN and 221 (93%) of 237 assigned to LAB were eligible for analysis. CLIN was not non-inferior to LAB; the mean increase in CD4 cell count was 175 cells per μL (SD 190, 95% CI 151-200) with CLIN and 206 (190, 181-231) with LAB (difference -31 [-63 to 2] and non-inferiority margin -52 [-58 to -45]). Furthermore, in the predefined secondary outcome of treatment changes, 13 participants (6%) in the LAB group switched to second-line regimens whereas no participants in the CLIN group did so (p<0·0001). By contrast, other predefined secondary outcomes were much the same in both groups-viral suppression (<40 copies per mL; 465 [49%] of 952 measurements in CLIN vs 456 [52%] of 884 in LAB), HIV resistance (23 [10%] of 238 participants vs 22 [10%] of 219 participants), mortality (44 [18%] of 238 vs 32 [14%] of 221), disease progression (85 [36%] of 238 vs 64 [29%] of 221), adherence (672 [63%] of 1067 measurements vs 621 [61%] of 1011), loss to follow-up (21 [9%] of 238 vs 17 [8%] of 221), and toxic effects (46 [19%] of 238 vs 56 [25%] of 221).
Our findings support WHO's recommendation for laboratory monitoring of antiretroviral therapy. However, the small differences that we noted between the strategies suggest that clinical monitoring alone could be used, at least temporarily, to expand antiretroviral therapy in low-resource settings.
French National Agency for Research on AIDS (ANRS) and Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER).
在资源匮乏的国家扩大抗逆转录病毒疗法是基于在农村设施中进行分散、综合的艾滋病毒护理；然而，一般来说，实验室监测是不可用的。我们旨在评估临床监测（CLIN）在非劣效性方面与实验室和临床监测（LAB）相比的有效性和安全性。
我们在喀麦隆的 9 家农村地区医院进行了一项随机、开放标签、非劣效性试验。合格的参与者是感染 HIV-1 组 M（WHO 疾病分期 3-4）的成年人（≥18 岁），他们以前没有接受过抗逆转录病毒治疗，并且在常规活动中由卫生保健工作者进行为期 2 年的随访。我们使用计算机生成的列表以 1:1 的比例随机分配参与者到 CLIN 或 LAB（每 6 个月进行一次 HIV 病毒载量和 CD4 细胞计数）组。主要结局是 CLIN 在增加 CD4 细胞计数方面不劣于 LAB，非劣效性边界为 25%。我们在至少参加了一次随访的参与者中进行了所有分析。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00301561。
256 名分配到 CLIN 的参与者中有 238 名（93%）和 237 名分配到 LAB 的参与者中有 221 名（93%）符合分析条件。CLIN 并不优于 LAB；CD4 细胞计数的平均增加量为 175 个细胞/μL（SD 190，95%CI 151-200），CLIN 为 206（190，181-231），LAB 为 206（190，181-231）（差异-31 [-63 至 2]，非劣效性边界-52 [-58 至-45]）。此外，在预先确定的次要结局中，LAB 组有 13 名（6%）参与者转为二线方案，而 CLIN 组没有参与者这样做（p<0·0001）。相比之下，两组的其他预先确定的次要结局非常相似-病毒抑制（<40 拷贝/毫升；CLIN 组 952 次测量中有 465 次[49%]，LAB 组 884 次中有 456 次[52%]），HIV 耐药性（23 名[10%]参与者对 238 名参与者中的 22 名[10%]参与者），死亡率（44 名[18%]对 238 名参与者中的 32 名[14%]），疾病进展（85 名[36%]对 238 名参与者中的 64 名[29%]），依从性（672 名[63%]对 1067 次测量中的 621 名[61%]），失访（21 名[9%]对 238 名参与者中的 17 名[8%]）和毒性作用（46 名[19%]对 238 名参与者中的 56 名[25%]）。
我们的发现支持世卫组织关于抗逆转录病毒疗法实验室监测的建议。然而，我们注意到这两种策略之间的差异很小，这表明在资源匮乏的环境中，单独使用临床监测至少可以暂时扩大抗逆转录病毒治疗。
法国国家艾滋病研究署（ANRS）和 Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau（ESTHER）。
