Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study.
Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study.
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DOI：
10.1016/s1473-3099(14)70020-9
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发表时间：
2014-05
影响因子：
56.3
通讯作者：
Corey, Lawrence
中科院分区：
文献类型：
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作者：
Gray, Glenda E.;Moodie, Zoe;Metch, Barbara;Gilbert, Peter B.;Bekker, Linda-Gail;Churchyard, Gavin;Nchabeleng, Maphoshane;Mlisana, Koleka;Laher, Fatima;Roux, Surita;Mngadi, Kathryn;Innes, Craig;Mathebula, Matsontso;Allen, Mary;McElrath, M. Julie;Robertson, Michael;Kublin, James;Corey, Lawrence
Phambili研究在南非的主要异性恋人群中进行，评价了MRK Ad 5 gag/pol/nef亚型B HIV-1预防疫苗的有效性。当在美洲、加勒比海和澳大利亚评价相同疫苗的Step研究因非有效性而揭盲时，停止入组和疫苗接种，受试者揭盲，并延长随访时间，疫苗接种者中的HIV感染多于安慰剂接种者[ZM 1]。报告了整个随访期间的广泛分析，其中大部分是揭盲的。Phambili参与者是未感染HIV-1的性活跃男性和女性，年龄在18-35岁之间，随访3.5年。在第0、12、30周进行HIV检测和风险降低咨询，并在揭盲后改为3个月一次。使用考克斯比例风险模型估计HIV-1感染风险比（HR），比较疫苗接种者和安慰剂接种者，总体和亚组内。在随访早期揭盲的参与者中评价了长期疫苗有效性。在入组的801例受试者中（400例疫苗，401例安慰剂），112例（28%）接受了1次疫苗接种，259例（65%）接受了2次疫苗接种，29例（7%）接受了3次疫苗接种。与安慰剂组（n=37）相比，疫苗组（n=63）中发生的感染更多（校正HR（疫苗：安慰剂）1.70，95% CI 1.13-2.55，p = 0.01）。我们发现感染率没有随着接种疫苗的次数而增加，并且HR没有因性别、包皮环切术或Ad 5血清状态而异。基线或研究期间的风险行为差异或差异脱落（p=0.40）不太可能解释接种者中HIV-1感染率增加的原因。无论接受的剂量多少，HIV-1感染的HR增加，需要进一步研究以了解生物学机制。没有必要进一步将Ad 5载体用于HIV疫苗
The Phambili study, conducted in South Africa amongst a predominantly heterosexual population, evaluated the efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine. Enrollment and vaccinations were stopped, participants unblinded, and follow-up extended when the Step study evaluating the same vaccine in the Americas, Caribbean and Australia was unblinded for non-efficacy with more HIV infections amongst vaccinee than placebo recipients [ZM1]. Extensive analyses over the complete follow-up period, most of which was unblinded, are reported. Phambili participants were HIV-1 uninfected, sexually active men and women aged 18–35 years, followed for 3.5 years. HIV testing and risk reduction counseling occurred at weeks 0, 12, 30 and were switched to a 3 monthly schedule after unblinding. Cox proportional hazards models were used to estimate HIV-1 infection hazard ratios (HR) comparing vaccine to placebo recipients, overall and within subgroups. Long-term vaccine efficacy was evaluated in participants who were unblinded early in follow-up. Of the 801 participants enrolled (400 vaccine, 401 placebo), 112 (28%) received 1 vaccination, 259 (65%) 2 vaccinations and 29(7%) 3 vaccinations. More infections occurred in vaccinees (n=63) as compared to placebo (n=37) (adjusted HR (vaccine:placebo) 1.70, 95% CI 1.13–2.55, p = 0.01). We found no increase in infections with the number of vaccinations received and that the HRs did not differ by gender, circumcision, or Ad5 serostatus. Differences in risk behavior at baseline or during the study, or differential drop-out (p=0.40) are unlikely explanations for the increased rate of HIV-1 infections seen in vaccinees. The increased HR of HIV-1 acquisition, irrespective of number of doses received, warrants further investigation to understand the biological mechanism. Further use of the Ad5 vector for HIV vaccines is not warranted