From Queen Mary University of London, London (C.O.), and ViiV Healthcare, Brentford (V.C.) - both in the United Kingdom; EPIMED, Berlin (K.A.); Fundación Jiménez Díaz, Madrid (M.G.H.-M.); Central Research Institute of Epidemiology, Moscow (V.P.); the University of Alabama at Birmingham, Birmingham (E.T.O.); Hôpital Saint Antoine, Paris (P.-M.G.), and Hôpital Européen, Marseille (P. Philibert) - both in France; the National Center for Global Health and Medicine, Tokyo (S.O.); the University Health Network, University of Toronto, Toronto (S.W.), and GlaxoSmithKline, Mississauga (S.L.F., D.D.) - both in Ontario, Canada; North Texas Infectious Disease Consultants, Dallas (C. Bettacchi), and Central Texas Clinical Research, Austin (C. Brinson); Josha Research, Bloemfontein, South Africa (J.L.); ViiV Healthcare, Research Triangle Park, NC (M.S.C., P. Patel, R.D., A.C., S.G., D.A.M., K.Y.S., W.R.S.); and Janssen Research and Development, Beerse, Belgium (H.C., S.V., P.E.W., W.P.).
N Engl J Med. 2020 Mar 19;382(12):1124-1135. doi: 10.1056/NEJMoa1909512. Epub 2020 Mar 4.
Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection.
We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine. Participants who had an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were randomly assigned (1:1) to continue the current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly injections of long-acting cabotegravir plus rilpivirine. The primary end point was the percentage of participants who had an HIV-1 RNA level of 50 copies per milliliter or higher at week 48 (Food and Drug Administration snapshot algorithm).
At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 participants (2.1%) who received long-acting therapy and in 7 of 283 (2.5%) who received oral therapy (adjusted difference, -0.4 percentage points; 95% confidence interval [CI], -2.8 to 2.1), a result that met the criterion for noninferiority for the primary end point (margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy (adjusted difference, 0.4 percentage points; 95% CI, -3.7 to 4.5), a result that met the criterion for noninferiority for this end point (margin, -10 percentage points). Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy; 91% preferred long-acting therapy at week 48.
Therapy with long-acting cabotegravir plus rilpivirine was noninferior to oral therapy with dolutegravir-abacavir-lamivudine with regard to maintaining HIV-1 suppression. Injection-site reactions were common. (Funded by ViiV Healthcare and Janssen; FLAIR ClinicalTrials.gov number, NCT02938520.).
长效注射方案可能使人类免疫缺陷病毒 1 型（HIV-1）感染者的治疗变得更加简化。
我们进行了一项 3 期、随机、开放标签试验，将未接受过抗逆转录病毒治疗的 HIV-1 感染者接受 20 周的每日口服诱导治疗，包括度鲁特韦-阿巴卡韦-拉米夫定。16 周后 HIV-1 RNA 水平低于 50 拷贝/毫升的参与者被随机分配（1:1），继续目前的口服治疗或转换为口服卡替拉韦/利匹韦林治疗 1 个月，然后每月注射长效卡替拉韦/利匹韦林。主要终点是第 48 周时 HIV-1 RNA 水平为 50 拷贝/毫升或更高的参与者比例（食品和药物管理局快照算法）。
第 48 周时，长效治疗组有 6 例（2.1%）和口服治疗组有 7 例（2.5%）HIV-1 RNA 水平为 50 拷贝/毫升或更高（调整差异，-0.4 个百分点；95%置信区间[CI]，-2.8 至 2.1），达到主要终点非劣效性标准（边界为 6 个百分点）。长效治疗组有 93.6%和口服治疗组有 93.3%的患者在第 48 周时 HIV-1 RNA 水平低于 50 拷贝/毫升（调整差异，0.4 个百分点；95%CI，-3.7 至 4.5），达到该终点非劣效性标准（边界为-10 个百分点）。接受长效治疗的参与者中，86%报告注射部位反应（中位持续时间 3 天；轻度或中度严重程度，99%的病例）；4 名参与者因注射相关原因退出试验。长效治疗组分别有 11%和 2%的参与者出现 3 级或更高的不良事件和符合肝脏相关停药标准的事件，口服治疗组分别为 4%和 1%。在参与者转换为长效治疗后，治疗满意度增加；91%的人在第 48 周时更喜欢长效治疗。
长效卡替拉韦/利匹韦林治疗与口服多替拉韦/阿巴卡韦/拉米夫定治疗在维持 HIV-1 抑制方面非劣效。注射部位反应常见。（由 ViiV 医疗保健公司和杨森公司资助；FLAIR 临床试验.gov 编号，NCT02938520。）
