Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial
Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s0140-6736(08)61842-5
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发表时间：
2008-12-06
期刊：
影响因子：
168.9
通讯作者：
Lahteenmaki, Pekka
中科院分区：
文献类型：
--
作者：
Skoler-Karpoff, Stephanie;Ramjee, Gita;Lahteenmaki, Pekka
迫切需要由女性发起的艾滋病毒预防方案，如杀微生物剂。我们评估Carraguard，一种角叉菜胶为基础的化合物开发的人口理事会，其有效性和长期的安全性，在预防HIV infection in women.Methods我们进行了一项随机，安慰剂对照，双盲试验，在南非的三个网站的性活跃，HIV阴性的妇女，年龄7.6岁及以上。6202名参与者通过区组随机化方案随机分配到Carraguard（n=3103）或安慰剂（甲基纤维素[n=3099]）组，指导他们在每次阴道性行为期间使用一个凝胶涂抹器加避孕套。参与者被随访长达2年。每3个月一次的访问包括艾滋病毒存在和怀孕检测、盆腔检查、减少风险咨询以及治疗可治愈的性传播感染和有症状的阴道感染。主要结局是至HIV血清转换的时间。在疗效人群中进行分析（意向治疗人群的一个子集，不包括无法评估疗效的受试者）。该研究在ClinicalTrials.gov注册，编号NCT 00213083。结果对于主要结果（HIV血清转换时间），我们分析了Carraguard组的3011名妇女和安慰剂组的2994名妇女。Carraguard组（134起事件）和安慰剂组（151起事件）的HIV发病率分别为3.3/100女性-年（95%CI 2.8-3-9）和3.8/100女性-年（95%CI 3.2-4.4），血清转换时间分布无显著差异（p=0.30）。协变量调整的风险比为0.87（95% CI 0.69-1.09）。自我报告的凝胶使用率（96.2% Carragntard，95.9%安慰剂）和避孕套使用率（64.两组的最后性行为相似。然而，根据涂抹器测试，估计平均只有42.1%的性行为使用了凝胶（41.1%的Carraguard，43%的安慰剂）。意向治疗人群中有1420名（23%）女性发生了不良事件（713名Carraguard，707名安慰剂），95名（2%）女性发生了与凝胶使用相关的不良事件（48名Carraguard，47名安慰剂）。严重的不良事件发生在72（2%）妇女在Carraguard组和78（3%）在安慰剂组，其中只有一个被认为可能与凝胶使用（安慰剂组）。解释这项研究并没有显示Carraguard的有效性，在预防阴道传播艾滋病毒。没有安全问题的记录。资助美国国际开发署，比尔和梅林达盖茨基金会。
Background Female-initiated HIV prevention options, such as microbicides, are urgently needed. We assessed Carraguard, a carrageenan-based compound developed by the Population Council, for its efficacy and long-term safety in prevention of HIV infection in women.Methods We undertook a randomised, placebo-controlled, double-blind trial in three South African sites in sexually-active, HIV-negative women, aged 7.6 years and older. 6202 participants, who were randomly assigned by a block randomisation scheme to Carraguard (n=3103) or placebo (methylcellulose [n=3099]), were instructed to use one applicator of gel plus a condom during each vaginal sex act. Participants were followed up for up to 2 years. Visits every 3 months included testing for HIV presence and pregnancy, pelvic examinations, risk reduction counselling, and treatment for curable sexually transmitted infections and symptomatic vaginal infections. The primary outcome was time to HIV seroconversion. Analysis was in the efficacy population (a subset of the intention-to-treat population, excluding participants for whom efficacy could not be assessed). This study is registered with ClinicalTrials.gov, number NCT00213083.Findings For the primary outcome (time to HIV seroconversion) we analysed 3011 women in the Carraguard group and 2994 in the placebo group. HIV incidence was 3.3 per 100 woman-years (95% CI 2.8-3-9) in the Carraguard group (134 events) and 3.8 per 100 woman-years (95% CI 3.2-4.4) in the placebo group (151 events), with no significant difference in the distribution of time to seroconversion (p=0.30). The covariate-adjusted hazard ratio was 0.87 (95% CI 0.69-1.09). Rates of self-reported gel use (96.2% Carragntard, 95.9% placebo) and condom use (64. 1% in both groups) at last sex acts were similar in both groups. On the basis of applicator testing, however, gel was estimated to have been used in only 42.1% of sex acts, on average (41.1% Carraguard, 43-1% placebo). 1420 (23%) women in the intention-to-treat population had adverse events (713 Carraguard, 707 placebo), and 95 (2%) women had adverse events that were related to gel use (48 Carraguard, 47 placebo). Serious adverse events occurred in 72 (2%) women in the Carraguard group and 78 (3%) in the placebo group, only one of which was considered possibly related to gel use (placebo group).Interpretation This study did not show Carraguard's efficacy in prevention of vaginal transmission of HIV. No safety concerns were recorded.Funding US Agency for International Development, Bill & Melinda Gates Foundation.