美国吉利德科学公司Moupali Das团队研究了每年接受两次Lenacapavir或每日F/TAF用于顺性别妇女预防艾滋病毒的效果。2024年7月24日出版的《新英格兰医学杂志》发表了这项成果。

顺性别妇女在接受、坚持和非常坚持使用暴露前预防措施预防人类免疫缺陷病毒（HIV）方面存在差距。

研究组在南非和乌干达进行了一项涉及青春期女孩和年轻女性的3期双盲随机对照试验。参与者按2:2:1的比例分配，每26周接受一次皮下注射Lenacapavir，每日口服恩曲他滨-替诺福韦艾拉酚胺（F/TAF），或每日口服恩曲他滨-富马酸替诺福韦二吡呋酯（F/TDF；活性对照）；所有参与者还接受了替代的皮下或口服安慰剂。通过比较筛查人群中HIV感染率与估计的背景发病率，评估了Lenacapavir和F/TAF的疗效，并评估了与F/TDF相比的相对疗效。

在5338名最初HIV阴性的参与者中，观察到55例HIV感染事件：Lenacapavir组2134名参与者中0例感染（每100人年0例；95%置信区间[CI]，0.00至0.19），F/TAF组2136名参与者中39例感染（每100人年2.02例；95%CI，1.44至2.76），F/TDF组1068名参与者中16例感染（每100人年1.69例；95%CI，0.96至2.74）。背景筛查人群（8094名参与者）的HIV发病率为每100人年2.41例（95%CI，1.82至3.19）。Lenacapavir的HIV发病率显著低于背景HIV发病率（发病率比，0.00；95%CI，0.00至0.04；P<0.001）和F/TDF的HIV发病者（发病率比率，0.00；95%CI，0.00至0.10；P<0.001）。

F/TAF的HIV发病率与背景HIV发病率没有显著差异（发病率比，0.84；95%CI，0.55至1.28；P=0.21），F/TAF和F/TDF之间没有观察到HIV发病率有意义差异的证据（发病率比率，1.20；95%CI：0.67至2.14）。对F/TAF和F/TDF的依从性较低。未发现任何安全问题。注射部位反应在Lenacapavir组（68.8%）比安慰剂注射组（F/TAF和F/TDF联合）（34.9%）更常见；Lenacapavir组有4名参与者（0.2%）因注射部位反应而停止试验方案。

研究结果表明，每年接受两次Lenacapavir的参与者中没有人发生HIV感染。Lenacapavir的HIV发病率显著低于背景HIV发病率和F/TDF的HIV感染率。

附：英文原文

Title: Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women

Author: Linda-Gail Bekker, Moupali Das, Quarraisha Abdool Karim, Khatija Ahmed, Joanne Batting, William Brumskine, Katherine Gill, Ishana Harkoo, Manjeetha Jaggernath, Godfrey Kigozi, Noah Kiwanuka, Philip Kotze, Limakatso Lebina, Cheryl E. Louw, Moelo Malahleha, Mmatsie Manentsa, Leila E. Mansoor, Dhayendre Moodley, Vimla Naicker, Logashvari Naidoo, Megeshinee Naidoo, Gonasagrie Nair, Nkosiphile Ndlovu, Thesla Palanee-Phillips, Ravindre Panchia, Saresha Pillay, Disebo Potloane, Pearl Selepe, Nishanta Singh, Yashna Singh, Elizabeth Spooner, Amy M. Ward, Zwelethu Zwane, Ramin Ebrahimi, Yang Zhao, Alexander Kintu, Chris Deaton, Christoph C. Carter, Jared M. Baeten, Flavia Matovu Kiweewa

Issue&Volume: 2024-07-24

Abstract:

BACKGROUND

There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women.

METHODS

We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo. We assessed the efficacy of lenacapavir and F/TAF by comparing the incidence of HIV infection with the estimated background incidence in the screened population and evaluated relative efficacy as compared with F/TDF.

RESULTS

Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74). Background HIV incidence in the screened population (8094 participants) was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio, 0.84; 95% CI, 0.55 to 1.28; P=0.21), and no evidence of a meaningful difference in HIV incidence was observed between F/TAF and F/TDF (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). Adherence to F/TAF and F/TDF was low. No safety concerns were found. Injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.9%); 4 participants in the lenacapavir group (0.2%) discontinued the trial regimen owing to injection-site reactions.

CONCLUSIONS

No participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF.

DOI: NJ202407240000001

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2407001