Landovitz Raphael J, Tao Li, Yang Juan, de Boer Melanie, Carter Christoph, Das Moupali, Baeten Jared M, Liu Albert, Hoover Karen W, Celum Connie, Grinsztejn Beatriz, Morris Sheldon, Wheeler Darrell P, Mayer Kenneth H, Golub Sarit A, Bekker Linda-Gail, Diabaté Souleymane, Hoornenborg Elske, Myers Janet, Leech Ashley A, McCormack Sheena, Chan Philip A, Sweat Michael, Matthews Lynn T, Grant Robert
UCLA Center for Clinical AIDS Research and Education, Los Angeles, California, USA.
Gilead Sciences, Inc, Foster City, California, USA.
Clin Infect Dis. 2024 Nov 22;79(5):1197-1207. doi: 10.1093/cid/ciae143.
Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings.
HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies.
Among 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]: .63-.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/wk, respectively, and the corresponding incidence was 3.9 (95% CI: 2.9-5.3), .24 (.060-.95), .27 (.12-.60), and .054 (.008-.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports.
Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.
恩曲他滨/替诺福韦酯（F/TDF）口服暴露前预防（PrEP）对HIV-1感染具有高效性。开展了72项每日口服F/TDF PrEP的前瞻性研究，以评估不同环境下的HIV-1发病率、耐药性、依从性以及骨骼和肾脏安全性。
根据PrEP开始后及停药60天内确诊的新发HIV-1病例计算HIV-1发病率。在部分研究中评估了干血斑（DBS）中的替诺福韦浓度、耐药性以及骨骼/肾脏安全性指标。
在17274名参与者中，有101例新发HIV-1诊断病例（每100人年0.77例；95%置信区间[CI]：0.63 - 0.94）。在78例有耐药数据的病例中，18例（23%）有M184I或V突变，1例（1.3%）有K65R突变，3例（3.8%）同时有这两种突变。在54例有DBS替诺福韦浓度数据的病例中，平均依从性<2剂/周、2 - 3剂/周、4 - 6剂/周和≥7剂/周的分别有45例（83.3%）、2例（3.7%）、6例（11.1%）和1例（1.9%），相应的发病率分别为每100人年3.9例（95%CI：2.9 - 5.3）、0.24例（0.060 - 0.95）、0.27例（0.12 - 0.60）和0.054例（0.008 - 0.38）。年轻参与者、西班牙裔/拉丁裔和黑人参与者、顺性别女性以及跨性别女性的依从性较低。骨骼和肾脏不良事件发病率分别为每100人年0.69例和11.8例，与先前报告一致。
利用迄今为止全球PrEP研究的最大汇总分析，我们证明F/TDF在不同的临床环境、地域、人群以及HIV-1暴露途径中都是安全且高效的，即使给药频率低于每日一次。
