Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women

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Citações na Scopus
325
Tipo de produção
article
Data de publicação
2021
Título da Revista
ISSN da Revista
Título do Volume
Editora
MASSACHUSETTS MEDICAL SOC
Autores
LANDOVITZ, Raphael J.
DONNELL, Deborah
CLEMENT, Meredith E.
HANSCOM, Brett
COTTLE, Leslie
COELHO, Lara
CABELLO, Robinson
CHARIYALERTSAK, Suwat
DUNNE, Eileen F.
FRANK, Ian
Citação
NEW ENGLAND JOURNAL OF MEDICINE, v.385, n.7, p.595-608, 2021
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Injectable Cabotegravir for Prevention of HIV Infection Antiviral medication has emerged as an important tool in the prevention of HIV infection. In this randomized, controlled trial, an injectable long-acting agent, cabotegravir, was found to be superior to daily oral tenofovir disoproxil fumarate-emtricitabine in preventing incident HIV infection in cisgender men and transgender women who have sex with men. Background Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. Methods We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. Results The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. Conclusions CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, .)
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Referências
  1. Andrews CD, 2017, AIDS, V31, P461, DOI 10.1097/QAD.0000000000001343
  2. Andrews CD, 2014, SCIENCE, V343, P1151, DOI 10.1126/science.1248707
  3. [Anonymous], 2020, 2020 GLOBAL AIDS UPD
  4. Baeten JM, 2012, NEW ENGL J MED, V367, P399, DOI 10.1056/NEJMoa1108524
  5. Barbee LA, 2017, SEX TRANSM DIS, V44, P385, DOI 10.1097/OLQ.0000000000000614
  6. Bourgi K, 2020, CLIN INFECT DIS, V70, P1267, DOI 10.1093/cid/ciz407
  7. Castillo-Mancilla JR, 2013, AIDS RES HUM RETROV, V29, P384, DOI [10.1089/aid.2012.0089, 10.1089/AID.2012.0089]
  8. Choopanya K, 2013, LANCET, V381, P2083, DOI 10.1016/S0140-6736(13)61127-7
  9. COCKCROFT DW, 1976, NEPHRON, V16, P31, DOI 10.1159/000180580
  10. Department of Health and Human Services National Institutes of Health National Institute of Allergy and Infectious Diseases, 2017, DIV AIDS DAIDS TABL DIV AIDS DAIDS TABL
  11. Dobard C, 2020, J INFECT DIS, V222, P391, DOI 10.1093/infdis/jiaa095
  12. EMERSON SS, 1990, BIOMETRIKA, V77, P875, DOI 10.2307/2337110
  13. Grant RM, 2014, LANCET INFECT DIS, V14, P820, DOI 10.1016/S1473-3099(14)70847-3
  14. Grant RM, 2010, NEW ENGL J MED, V363, P2587, DOI 10.1056/NEJMoa1011205
  15. Hoornenborg E, 2017, LANCET HIV, V4, pE522, DOI 10.1016/S2352-3018(17)30132-7
  16. Landovitz RJ, 2020, LANCET HIV, V7, pE472, DOI 10.1016/S2352-3018(20)30106-5
  17. Landovitz RJ, 2018, PLOS MED, V15, DOI 10.1371/journal.pmed.1002690
  18. Markowitz M, 2017, LANCET HIV, V4, pE331, DOI 10.1016/S2352-3018(17)30068-1
  19. Marrazzo JM, 2015, NEW ENGL J MED, V372, P509, DOI 10.1056/NEJMoa1402269
  20. Marzinke MA., 2021, J INFECT DIS
  21. Mayer KH, 2020, LANCET, V396, P239, DOI 10.1016/S0140-6736(20)31065-5
  22. Molina JM, 2015, NEW ENGL J MED, V373, P2237, DOI 10.1056/NEJMoa1506273
  23. Muller RH, 2011, EUR J PHARM BIOPHARM, V78, P1, DOI 10.1016/j.ejpb.2011.01.007
  24. Murnane PM, 2013, AIDS, V27, P2155, DOI 10.1097/QAD.0b013e3283629037
  25. Sax PE, 2020, CLIN INFECT DIS, V71, P1379, DOI 10.1093/cid/ciz999
  26. Solomon MM, 2014, CLIN INFECT DIS, V59, P1020, DOI 10.1093/cid/ciu450
  27. Spreen W, 2014, JAIDS-J ACQ IMM DEF, V67, P481, DOI 10.1097/QAI.0000000000000301
  28. Tansey C, 2018, J INFECT DIS, V217, P1139, DOI 10.1093/infdis/jix669
  29. Thigpen MC, 2012, NEW ENGL J MED, V367, P423, DOI 10.1056/NEJMoa1110711
  30. Venter WDF, 2019, NEW ENGL J MED, V381, P803, DOI 10.1056/NEJMoa1902824