Author
Affilliation
Abstract
HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections included 7 with CAB administration within 6 months of the first HIV-positive visit (2 with on-time injections, 3 with ≥1 delayed injection, and 2 who restarted CAB) and 11 with no recent CAB administration. Three cases had integrase strand transfer inhibitor (INSTI) resistance (2 with on-time injections and 1 who restarted CAB). Among 34 CAB infections analyzed to date, diagnosis delays and INSTI resistance were significantly more common in infections with CAB administration within 6 months of the first HIV-positive visit. This report further characterizes HIV infections in persons receiving CAB preexposure prophylaxis and helps define the impact of CAB on the detection of infection and the emergence of INSTI resistance.
Publisher
American Society for Microbiology
Citation
MARZINKE, Mark A. et al. Extended Analysis of HIV Infection in Cisgender Men and Transgender Women Who Have Sex with Men Receiving Injectable Cabotegravir for HIV Prevention: HPTN 083. Antimicrobial Agents and Chemotherapy, v. 67, n. 4, p. 1-13, Apr. 2023.
DOI
10.1128/aac.00053-23
ISSN
0066-4804
Notes
We thank the HPTN 083 study team and participants; the HPTN 083 site principal investigators (PIs); the laboratory staff at the study sites and the HPTN Laboratory Center; laboratory staff at the University of Pittsburgh; Christos Petropoulos, Michael Seisa, Yolanda Lie, and laboratory staff at Monogram Biosciences; the members of the HPTN 083 Endpoint Adjudication Committee and HIV Alias Committee (William Meyer, Jeanne Marrazzo, Carole Wallis, Aida Asmelash, and Eric Daar) and investigators at ViiV Healthcare; and Richard Clark and other investigators at Gilead Sciences. This work was supported by the National Institute of Allergy and Infectious Diseases, Office of the Director, National Institutes of Health; the National Institute of Mental Health; the National Institute on Drug Abuse; and the Eunice Kennedy Shriver Institute for Child Health and Human Development under award numbers UM1AI068619 (HIV Prevention Trials Network [HPTN] Leadership and Operations Center [Ryan Kofron, Marybeth McCauley, Suwat Chariyalertsak, Kenneth Mayer, Roberto C. Arduino, Myron S. Cohen, Beatriz Grinsztejn, and Raphael J. Landovitz]), UM1AI068617 (HPTN Statistical and Data Management Center [Zhe Wang, Lei Weng, and Brett Hanscom]), and UM1AI068613 (HPTN Laboratory Center [Mark A. Marzinke, Jessica M. Fogel, Estelle Piwowar-Manning, Amber Moser, Pradip Bhandari, Ryann Gollings, Lane R. Bushman, Peter L. Anderson, Deborah Persaud, Craig W. Hendrix, and Susan H. Eshleman]). ViiV Healthcare and Gilead Sciences donated trial medications and matching placebos. ViiV Healthcare provided additional funding. The individuals noted above received direct funding support for the conduct of the HPTN 083 trial and the work described in this report. The content of the report is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, ViiV Healthcare, or Gilead Sciences. All authors participated in the study, contributed to manuscript preparation, and reviewed the manuscript. Additional roles are as follows. Mark A. Marzinke, lead laboratory pharmacologist, designed the study, coordinated pharmacology testing, and analyzed data. Jessica M. Fogel, HPTN Laboratory Center virologist, analyzed data and drafted the manuscript. Zhe Wang, HPTN SDMC data analyst, performed data management and analysis. Estelle Piwowar-Manning, HPTN Laboratory Center deputy director, coordinated laboratory testing. Ryan Kofron provided graphic arts support. Amber Moser and Pradip Bhandari assisted with sample management and testing. Ryann Gollings and Lane R. Bushman assisted with pharmacology testing. Lei Weng assisted with data management. Elias K. Halvas performed low-viral-load INSTI genotyping. John Mellors provided input on HIV virology. Peter L. Anderson was responsible for TFV-DP testing. Deborah Persaud was responsible for HIV DNA testing. Craig W. Hendrix is the HPTN 083 protocol pharmacologist. Marybeth McCauley is the HPTN 083 study coordinator. Alex R. Rinehart, Marty St Clair, Susan L. Ford, and James F. Rooney provided pharmaceutical support. Adeola Adeyeye is the HPTN 083 NIH medical officer. Suwat Chariyalertsak is the PI for the HPTN 083 site in Chiang Mai, Thailand. Kenneth Mayer is the PI for the HPTN 083 site in Boston, MA. Roberto C. Arduino is the PI for the HPTN 083 site in Houston, TX. Myron S. Cohen is the HPTN Leadership and Operations Center PI. Beatriz Grinsztejn is the HPTN 083 protocol cochair. Brett Hanscom is the HPTN 083 statistician. Raphael J. Landovitz, HPTN 083 protocol chair, designed the study, analyzed data, and drafted the manuscript. Susan H. Eshleman, HPTN 083 protocol virologist, designed the study, analyzed data, and drafted the manuscript. None of the authors has a commercial or other association that might pose a conflict of interest, with the following exceptions. Raphael J. Landovitz has served on scientific advisory boards for Gilead and Merck and has received honoraria from Roche and Janssen.
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