Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons

被引：54

作者：

Kelley, Colleen F. ^{[1
,2
]}

Acevedo-Quinones, Maribel ^{[30
]}

Agwu, Allison L. ^{[4
,5
]}

Avihingsanon, Anchalee ^{[31
,32
]}

Benson, Paul ^{[6
,14
]}

Blumenthal, Jill ^{[7
]}

Brinson, Cynthia ^{[15
]}

Brites, Carlos ^{[34
]}

Cahn, Pedro ^{[41
]}

Cantos, Valeria D. ^{[3
]}

Clark, Jesse ^{[8
]}

Clement, Meredith ^{[17
]}

Creticos, Cathy ^{[18
]}

Crofoot, Gordon ^{[16
]}

Diaz, Ricardo S. ^{[35
]}

Doblecki-Lewis, Susanne ^{[20
]}

Gallardo-Cartagena, Jorge A. ^{[43
]}

Gaur, Aditya ^{[24
]}

Grinsztejn, Beatriz ^{[38
]}

Hassler, Shawn ^{[11
]}

Hinojosa, Juan Carlos ^{[45
]}

Hodge, Theo ^{[25
]}

Kaplan, Richard ^{[46
]}

Lacerda, Marcus ^{[39
]}

Lamarca, Anthony ^{[21
]}

Losso, Marcelo H. ^{[42
]}

Madruga, Jose Valdez ^{[36
]}

Mayer, Kenneth H. ^{[26
]}

Mills, Anthony ^{[12
]}

Mounzer, Karam ^{[27
]}

Ndlovu, Nkosiphile ^{[47
]}

Novak, Richard M. ^{[19
]}

Rios, Alma Perez ^{[49
]}

Phanuphak, Nittaya ^{[33
]}

Ramgopal, Moti ^{[22
]}

Ruane, Peter J. ^{[9
]}

Sanchez, Jorge ^{[43
]}

Santos, Breno ^{[40
]}

Schine, Patric ^{[13
]}

Schreibman, Tanya ^{[23
]}

Spencer, LaShonda Y. ^{[10
]}

Van Gerwen, Olivia T. ^{[28
]}

Vasconcelos, Ricardo ^{[37
]}

Vasquez, Jose Gabriel ^{[44
]}

Zwane, Zwelethu ^{[48
]}

Cox, Stephanie ^{[14
]}

Deaton, Chris ^{[50
]}

Ebrahimi, Ramin ^{[14
]}

Wong, Pamela ^{[14
]}

Singh, Renu ^{[14
]}

机构：

[1] Emory Univ, Sch Med, Hope Clin, Decatur, GA USA

[2] Grady Hlth Syst, Atlanta, GA USA

[3] Emory Univ, Ponce de Leon Ctr Clin Res Site, Div Infect Dis, HIV AIDS Clin Trials Unit, Atlanta, GA USA

[4] Johns Hopkins Univ, Sch Med, Div Pediat, Baltimore, MD USA

[5] Johns Hopkins Univ, Sch Med, Div Adult Infect Dis, Baltimore, MD USA

[6] Be Well Med Ctr, Berkley, MI USA

[7] Univ Calif San Diego, Dept Med, San Diego, CA USA

[8] Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA

[9] Charles R Drew Univ, Ruane Clin Res, Los Angeles, CA USA

[10] Charles R Drew Univ, Drew Ctr AIDS Res Educ & Serv, Los Angeles, CA USA

[11] Optimus Med Grp StudyOps, San Francisco, CA USA

[12] Mills Clin Res, West Hollywood, CA USA

[13] Bios Clin Res, Palm Springs, CA USA

[14] Gilead Sci, 333 Lakeside Dr, Foster City, CA 94404 USA

[15] Cent Texas Clin Res, Austin, TX USA

[16] Crofoot MD Clin & Res Ctr, Houston, TX USA

[17] Louisiana State Univ, Hlth Sci Ctr New Orleans, Dept Infect Dis, New Orleans, LA USA

[18] Howard Brown Hlth, Chicago, IL USA

[19] Univ Illinois Hlth Sci, Div Infect Dis, Chicago, IL USA

[20] Univ Miami, Miller Sch Med, Div Infect Dis, Miami, FL USA

[21] Therafirst Med Ctr, Ft Lauderdale, FL USA

[22] Midway Immunol & Res Ctr, Ft Pierce, FL USA

[23] CAN Community Hlth, Sarasota, FL USA

[24] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN USA

[25] Washington Hlth Inst, Washington, DC USA

[26] Fenway Hlth Med Clin, Boston, MA USA

[27] Philadelphia FIGHT Community Hlth Ctr, Jonathan Lax Treatment Ctr, Philadelphia, PA USA

[28] Univ Alabama Birmingham, Dept Med, Div Infect Dis, Birmingham, AL USA

[29] Yale Sch Med, Sect Infect Dis, New Haven, CT USA

[30] Ctr Ararat, San Juan, PR USA

[31] Chulalongkorn Univ, Fac Med, Thai Red Cross AIDS Res Ctr, HIV Netherlands Australia Thailand Res Collaborat, Bangkok, Thailand

[32] Chulalongkorn Univ, Fac Med, Ctr Excellence TB, Bangkok, Thailand

[33] Pribta Tangerine Clin, Inst HIV Res & Innovat, Bangkok, Thailand

[34] Complexo Hosp Univ Prof Edgard Santos, Salvador, Brazil

[35] Univ Fed Sao Paulo, Sao Paulo, Brazil

[36] Ctr Referencia & Treinamento DST AIDS SP, Sao Paulo, Brazil

[37] Univ Sao Paulo, Hosp Clin, Fac Med, Sao Paulo, Brazil

[38] Fundacao Oswaldo Cruz, Inst Nacl Infectol Evandro Chagas, Rio De Janeiro, Brazil

[39] Fundacao Med Trop Doutor Heitor Vieira Dourado, Manaus, Brazil

[40] Hosp Nossa Senhora de Conceicao, Infect Dis Serv, Porto Alegre, Brazil

[41] Fdn Huesped, Buenos Aires, Argentina

[42] Hosp Gen Agudos Jose Maria Ramos Mejia, Buenos Aires, Argentina

[43] Univ Nacl Mayor San Marcos, Ctr Invest Tecnol Biomed & Medioambientales, Lima, Peru

[44] Via Libre, Lima, Peru

[45] Asociac Civil Selva Amazon, Iquitos, Peru

[46] Desmond Tutu Hlth Fdn, Cape Town, South Africa

[47] Univ Witwatersrand, Wits Reprod Hlth & HIV Inst, Fac Hlth Sci, Sch Publ Hlth, Johannesburg, South Africa

[48] Aurum Inst, Pretoria Clin Res Site, Pretoria, South Africa

[49] Ctr Invest Farmaceut Especializada Occidente, Guadalajara, Mexico

[50] Gilead Sci, Cambridge, England

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2024年

关键词：

TRANSGENDER WOMEN; CISGENDER MEN; CABOTEGRAVIR; EMTRICITABINE; INFECTION; TENOFOVIR; PHASE-3;

D O I：

10.1056/NEJMoa2411858

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear. METHODS In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF). The primary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with the background HIV incidence in the screened population. The secondary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with that in the F/TDF group. RESULTS Among 3265 participants who were included in the modified intention-to-treat analysis, HIV infections occurred in 2 participants in the lenacapavir group (0.10 per 100 person-years; 95% confidence interval [CI], 0.01 to 0.37) and in 9 participants in the F/TDF group (0.93 per 100 person-years; 95% CI, 0.43 to 1.77). The background HIV incidence in the screened population (4634 participants) was 2.37 per 100 person-years (95% CI, 1.65 to 3.42). The incidence of HIV infection in the lenacapavir group was significantly lower than both the background incidence (incidence rate ratio, 0.04; 95% CI, 0.01 to 0.18; P<0.001) and the incidence in the F/TDF group (incidence rate ratio, 0.11; 95% CI, 0.02 to 0.51; P = 0.002). No safety concerns were identified. A total of 26 of 2183 participants (1.2%) in the lenacapavir group and 3 of 1088 (0.3%) in the F/TDF group discontinued the trial regimen because of injection-site reactions. CONCLUSIONS The HIV incidence with twice-yearly lenacapavir was significantly lower than the background incidence and the incidence with F/TDF.

引用

页码：1261 / 1276

页数：16

共 54 条

[1] Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots following Directly Observed Therapy [J].

Anderson, Peter L. ;

Liu, Albert Y. ;

Castillo-Mancilla, Jose R. ;

Gardner, Edward M. ;

Seifert, Sharon M. ;

McHugh, Cricket ;

Wagner, Theresa ;

Campbell, Kayla ;

Morrow, Mary ;

Ibrahim, Mustafa ;

Buchbinder, Susan ;

Bushman, Lane R. ;

Kiser, Jennifer J. ;

MaWhinney, Samantha .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2018, 62 (01)

[2]

Appenroth M., 2021, NO DATA NO MORE MANI

[3] Replicate Aptima Assay for Quantifying Residual Plasma Viremia in Individuals on Antiretroviral Therapy [J].

Bakkour, Sonia ;

Deng, Xutao ;

Bacchetti, Peter ;

Grebe, Eduard ;

Montalvo, Leilani ;

Worlock, Andrew ;

Stone, Mars ;

Deeks, Steven G. ;

Richman, Douglas D. ;

Busch, Michael P. .

JOURNAL OF CLINICAL MICROBIOLOGY, 2020, 58 (12)

[4] Worldwide burden of HIV in transgender women: a systematic review and meta-analysis [J].

Baral, Stefan D. ;

Poteat, Tonia ;

Stromdahl, Susanne ;

Wirtz, Andrea L. ;

Guadamuz, Thomas E. ;

Beyrer, Chris .

LANCET INFECTIOUS DISEASES, 2013, 13 (03) :214-222

[5] Long-acting lenacapavir acts as an effective preexposure prophylaxis in a rectal SHIV challenge macaque model [J].

Bekerman, Elena ;

Yant, Stephen R. ;

Vanderveen, Laurie ;

Hansen, Derek ;

Lu, Bing ;

Rowe, William ;

Wang, Kelly ;

Callebaut, Christian .

JOURNAL OF CLINICAL INVESTIGATION, 2023, 133 (16)

[6] Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women [J].

Bekker, Linda-Gail ;

Das, Moupali ;

Karim, Quarraisha Abdool ;

Ahmed, Khatija ;

Batting, Joanne ;

Brumskine, William ;

Gill, Katherine ;

Harkoo, Ishana ;

Jaggernath, Manjeetha ;

Kigozi, Godfrey ;

Kiwanuka, Noah ;

Kotze, Philip ;

Lebina, Limakatso ;

Louw, Cheryl E. ;

Malahleha, Moelo ;

Manentsa, Mmatsie ;

Mansoor, Leila E. ;

Moodley, Dhayendre ;

Naicker, Vimla ;

Naidoo, Logashvari ;

Naidoo, Megeshinee ;

Nair, Gonasagrie ;

Ndlovu, Nkosiphile ;

Palanee-Phillips, Thesla ;

Panchia, Ravindre ;

Pillay, Saresha ;

Potloane, Disebo ;

Selepe, Pearl ;

Singh, Nishanta ;

Singh, Yashna ;

Spooner, Elizabeth ;

Ward, Amy M. ;

Zwane, Zwelethu ;

Ebrahimi, Ramin ;

Zhao, Yang ;

Kintu, Alexander ;

Deaton, Chris ;

Carter, Christoph C. ;

Baeten, Jared M. ;

Kiweewa, Flavia Matovu .

NEW ENGLAND JOURNAL OF MEDICINE, 2024, 391 (13) :1179-1192

[7]

Castagna A, 2023, HIV MED, V24, P203

[8]

Castillo-Mancilla JR, 2013, AIDS RES HUM RETROV, V29, P384, DOI [10.1089/AID.2012.0089, 10.1089/aid.2012.0089]

[9]

Centers for Disease Control and Prevention, 2024, HIV surveillance supplemental report: Estimated HIV incidence and prevalence in the United States, 2018-2022

[10]

Centers for Disease Control and Prevention, 2024, HIV surveillance report: Diagnoses, deaths, and prevalence of HIV in the United States and 6 territories and freely associated states

← 1 2 3 4 5 6 →