Mark A Marzinke1,2, Beatriz Grinsztejn3, Jessica M Fogel1, Estelle Piwowar-Manning1, Maoji Li4, Lei Weng4, Marybeth McCauley5, Vanessa Cummings1, Shahnaz Ahmed1, Casey D Haines2, Lane R Bushman6, Christos Petropoulos7, Deborah Persaud8, Adeola Adeyeye9, Ryan Kofron10, Alex Rinehart11, Marty St Clair11, James F Rooney12, Daniel Pryluka13, Lara Coelho3, Aditya Gaur14, Keren Middelkoop15, Nittaya Phanuphak16,17, Myron S Cohen18, Craig W Hendrix2, Peter Anderson6, Brett Hanscom4, Deborah Donnell4, Raphael J Landovitz19, Susan H Eshleman1. 1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 2. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 3. Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil. 4. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. 5. FHI 360, Durham, North Carolina, USA. 6. University of Colorado, Aurora, Colorado, USA. 7. Monogram Biosciences, South San Francisco, California, USA. 8. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 9. Prevention Science Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA. 10. Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA. 11. ViiV Healthcare, Research Triangle Park, North Carolina, USA. 12. Gilead Sciences, Foster City, California, USA. 13. Hospital Velez Sarfield, Buenos Aires, Argentina. 14. St Jude Children's Research Hospital, Memphis, Tennessee, USA. 15. Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. 16. Institute of HIV Research and Innovation, Bangkok, Thailand. 17. Center of Excellence in Transgender Health, Chulalongkorn University, Bangkok, Thailand. 18. Department of Medicine, University of North Carolina, North Carolina, USA. 19. Center for Clinical AIDS Research & Education, University of California, Los Angeles, Los Angeles, California, USA.
Abstract
BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083. METHODS: Retrospective testing included HIV testing, viral load testing, quantification of study drugs, and HIV drug resistance testing. RESULTS: Fifty-eight infections were evaluated, including 51 incident infections (12 in CAB arm and 39 in TDF/FTC arm). In many cases (5 in CAB arm and 37 in TDF/FTC arm), infection was associated with low or unquantifiable study drug concentrations. In 4 cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral therapy, and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing. CONCLUSIONS: Early detection of HIV infection and prompt antiretroviral therapy initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.
BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083. METHODS: Retrospective testing included HIV testing, viral load testing, quantification of study drugs, and HIV drug resistance testing. RESULTS: Fifty-eight infections were evaluated, including 51 incident infections (12 in CAB arm and 39 in TDF/FTC arm). In many cases (5 in CAB arm and 37 in TDF/FTC arm), infection was associated with low or unquantifiable study drug concentrations. In 4 cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral therapy, and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing. CONCLUSIONS: Early detection of HIV infection and prompt antiretroviral therapy initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.
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