H1N1pdm09 Adjuvanted Vaccination in HIV-Infected Adults: A Randomized Trial of Two Single versus Two Double Doses

BackgroundSince human immunodeficiency virus (HIV)-infected individuals are at increased risk of severe disease from pandemic influenza A (H1N1pdm09), vaccination was recommended as a prevention strategy. The aim of the present study was to evaluate the safety, immunogenicity and persistence of the immune response after vaccination against pandemic influenza A (H1N1pdm09) with an adjuvanted vaccine in human immunodeficiency virus (HIV)-infected adults using two single and two double doses. Methodology/Principal FindingsOpen label, randomized trial to evaluate the immune response following H1N1pdm09 vaccination in HIV-infected participants compared to HIV-negative controls (NCT01155037). HIV-infected participants were randomized to receive 2 single (3.75 µg hemagglutinin) or 2 double (7.5 µg hemagglutinin) doses of the vaccine, 21 days apart. Controls received one dose of the vaccine. The primary endpoint was seroconversion as measured by hemagglutination inhibition assay. Two hundred fifty six HIV-infected participants (129 and 127 randomized to single and double doses, respectively) and 71 HIV-negative controls were enrolled. Among HIV-infected participants, seroconversion increased from 46.7% and 51.7% after the first dose to 77.2% and 83.8% after the second dose of the vaccine using single and double doses, respectively. Participants aged >40 years showed higher seroconversion compared to younger participants. Seroconversion among HIV-infected women and those with nadir CD43 was significantly higher with double doses. Persistence of protective antibodies six months after vaccination was achieved by 80% and 89.9% of the HIV-infected participants who received single and double doses, respectively. Conclusions/SignificanceOur results support the recommendation of two double doses of adjuvanted H1N1pdm09 vaccine for HIV-infected individuals, particularly women, and those aged >40 years or with nadir CD43, to achieve antibody levels that are both higher and more sustained. Trial RegistrationClinicalTrials.gov NCT01155037背景：由于人类免疫缺陷病毒（human immunodeficiency virus, HIV）感染者罹患大流行甲型H1N1pdm09（pandemic influenza A (H1N1pdm09)）流感后重症风险显著升高，接种疫苗被推荐为针对性预防策略。本研究旨在评估佐剂大流行甲型H1N1pdm09流感疫苗接种后，HIV感染成人的接种安全性、免疫原性及免疫应答持久性，受试方案包含2次单剂量与2次双剂量接种策略。 方法与主要结果：本研究为开放标签随机试验（试验注册号NCT01155037），旨在对比HIV感染者与HIV阴性对照人群接种H1N1pdm09疫苗后的免疫应答。HIV感染者被随机分配至两个接种组：2次单剂量组（每剂含3.75 μg血凝素（hemagglutinin））与2次双剂量组（每剂含7.5 μg血凝素），两次接种间隔21天；对照人群仅接种1剂疫苗。本研究的主要终点为通过血凝抑制试验（hemagglutination inhibition assay）检测的血清转换率。本研究共纳入256名HIV感染者（单剂量组与双剂量组分别为129例和127例）及71名HIV阴性对照受试者。在HIV感染者中，单剂量组与双剂量组的血清转换率分别从首剂接种后的46.7%、51.7%提升至第二剂接种后的77.2%与83.8%。年龄＞40岁的受试者血清转换率高于年轻受试者。双剂量接种方案下，HIV感染女性以及伴nadir CD43异常者的血清转换率显著更高。接种疫苗6个月后，单剂量组与双剂量组的HIV感染者中分别有80%与89.9%维持了保护性抗体水平。 结论与意义：本研究结果支持为HIV感染者推荐2次双剂量佐剂H1N1pdm09疫苗接种方案，尤其适用于女性、年龄＞40岁或伴nadir CD43异常的人群，以获得更高且更持久的保护性抗体水平。 试验注册：ClinicalTrials.gov 注册号NCT01155037