Risk behaviour and time as covariates for efficacy of the HIV vaccine regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the Thai phase 3 efficacy trial RV 144.
Risk behaviour and time as covariates for efficacy of the HIV vaccine regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the Thai phase 3 efficacy trial RV 144.
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DOI：
10.1016/s1473-3099(12)70088-9
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发表时间：
2012-07
影响因子：
56.3
通讯作者：
Kim, Jerome H.
中科院分区：
文献类型：
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作者：
Robb, Merlin L.;Rerks-Ngarm, Supachai;Nitayaphon, Sorachai;Pitisuttithum, Punnee;Kaewkungwal, Jaranit;Kunasol, Prayura;Khamboonruang, Chirasak;Thongcharoen, Prasert;Morgan, Patricia;Benenson, Michael;Paris, Robert M.;Chiu, Joseph;Adams, Elizabeth;Francis, Donald;Gurunathan, Sanjay;Tartaglia, Jim;Gilbert, Peter;Stablein, Don;Michael, Nelson L.;Kim, Jerome H.
泰国III期HIV疫苗试验的适度有效性（VE 31.2%95%CI 1.1，51.2）首次证明疫苗可以预防HIV感染。年龄、性别、婚姻状况和风险等基线变量并没有改变疫苗的有效性（VE）。在这里，我们探讨了接种疫苗后6个月间隔的行为风险和有效性。在参与试验期间，每6个月用自填问卷评估一次行为风险。检查获得终点和早期病毒载量终点与随时间推移的风险状态的相互作用以及接种后的时间效应。在每个风险组中，艾滋病毒感染的风险都很低，但大多数参与者在研究期间至少报告了一次高风险行为（N= 9187，58%）。在事后分析中，将在研究随访期间至少一次被归类为高风险或上升风险的参与者与作为随时间变化协变量保持低风险或中等风险行为的参与者进行比较，风险状态和获取疗效的相互作用是显著的（P = 0.010），风险较低的个体获益更大。VE似乎在早期达到峰值，估计在初次接种后12个月内累积VE = 60%（95% CI 22 - 80%），并迅速下降。疫苗接种似乎不影响早期或晚期感染的病毒载量。未来的HIV疫苗试验必须认识到人群中挑战强度和风险异质性与治疗效果之间的潜在相互作用。泰国III期试验中测试的方案可能受益于延长的免疫接种时间表。
The Thai phase III HIV vaccine trial's modest efficacy (VE 31.2% 95% CI 1.1, 51.2) represents the first demonstration that a vaccine can protect against HIV acquisition. Baseline variables of age, gender, marital status, and risk did not modify vaccine efficacy (VE). Here we explore behavioral risk and efficacy at 6 monthly intervals following vaccination. Behavioral risk was assessed with a self-administered questionnaire every 6 months during trial participation. Both the acquisition endpoint and the early viral load endpoint are examined for interactions with risk status over time and temporal effects following vaccination. Risk for HIV acquisition is low in each risk group, but the majority of participants reported higher-risk behavior at least once during the study (N= 9187, 58%). In post-hoc analyses, comparing those participants categorized as high or rising risk at least once during study follow-up versus those who maintained low or medium risk behavior as a time-varying covariate, the interaction of risk status and acquisition efficacy is significant (P = 0.010) with greater benefit in the lower risk individuals. VE appears to peak early with an estimate of cumulative VE = 60% through 12 months after initial vaccination (95% CI 22 –80%), and declines quickly. Vaccination did not appear to affect viral load in either early or late infections. Future HIV vaccine trials must recognize potential interactions between challenge intensity and risk heterogeneity in the population and treatment effects. The regimen tested in the Thai phase III trial may benefit from extended immunization schedules.