HIV DNA Levels in Persons Who Acquired HIV in the Setting of Long-Acting Cabotegravir for HIV Prevention: Analysis of Cases from HPTN 083 and 084
Publication: AIDS Research and Human Retroviruses
Abstract
We evaluated HIV DNA levels in individuals who received long-acting cabotegravir (CAB-LA) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis in the HPTN 083 and 084 trials and had HIV DNA testing performed to help determine HIV status. HIV DNA testing was performed using peripheral blood mononuclear cell (PBMC) samples collected after a reactive HIV test was obtained at a study site. DNA was quantified using droplet digital PCR (lower limit of detection [LLOD]: 4.09 copies/million PBMCs). Final HIV status and the timing of the first HIV-positive visit were determined by an independent adjudication committee based on HIV test results from real-time site testing and retrospective testing at a centralized laboratory. HIV DNA testing was performed for 133 participants [21 HIV-positive (7 CAB-LA arm, 14 TDF/FTC arm) and 112 HIV-negative; 1–6 tests/person]. For persons with HIV, the time between the first HIV-positive visit and collection of the first sample for DNA testing was a median of 81 days for those receiving CAB-LA (range 41–246) and 11 days for those receiving TDF/FTC (range 3–127). Four (57.1%) of the seven CAB-LA cases with infection had a low initial DNA result [three detected <LLOD; one near the LLOD (4.2 copies/106 PBMCs); in 2/4 cases, the DNA level was still <10 copies/106 PBMCs ≥40 weeks after the first HIV-positive visit. In contrast, only 3/14 (21.4%) of the TDF/FTC cases had a low or negative initial DNA test result (one not detected; two <10 copies/106 PBMCs). In this study, the time between the first HIV-positive visit and the first DNA test was longer in the CAB-LA cases than the TDF/FTC cases. Despite this difference, low or undetectable DNA levels were more frequently observed in the CAB-LA cases. This suggests that CAB-LA exposure may limit seeding of the HIV reservoir in early infection.
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Published In
AIDS Research and Human Retroviruses
Copyright
Copyright 2024, Mary Ann Liebert, Inc., publishers.
History
Published online: 28 October 2024
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Authors’ Contributions
All authors participated in the study, contributed to article preparation, and reviewed the article. Additional roles are shown below. J.M.F.: Analyzed data and drafted the article. D.P.: Responsible for HIV DNA testing. E.P.-M.: HPTN LC Coordinator for HPTN 084. P.R.: HPTN LC Coordinator for HPTN 083. J.S.: Performed HIV DNA testing. M.A.M.: Responsible for pharmacology testing. Z.W.: Data analyst for HPTN 083. X.G.: Data analyst for HPTN 084. M.M.: Project Manager for HPTN 083. J.F.: Project Manager for HPTN 084. H.V.T.: Site PI for HPTN 083. C.U.: Site PI for HPTN 083. C.-A.M.: Site PI for HPTN 084. J.M.: Site PI for HPTN 084. A.R.R.: Provided pharmaceutical support. J.F.R.: Provided pharmaceutical support. M.S.C.: HPTN Leadership and Operations Center PI. B.H.: Protocol statistician for HPTN 084. B.G.: HPTN 083 Protocol Co-Chair. M.C.H.: HPTN 084 Protocol Co-Chair. S.D.-M.: HPTN 084 Protocol Chair. R.J.L.: HPTN 083 Protocol Chair. S.H.E.: Protocol Virologist for HPTN 083 and HPTN 084; designed the study, analyzed data, and drafted the article.
Author Disclosure Statement
None of the authors has a commercial or other association that might pose a conflict of interest, with the following exceptions: R.J.L. has served on scientific advisory boards for Merck, on a data safety monitoring board for RedQueen Therapeutics and as a consultant to Merck, ViiV Healthcare, and Gilead Sciences. A.R.R. is an employee of ViiV Healthcare. J.F.R. is an employee and stockholder of Gilead Sciences.
Funding Information
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), UM1AI068617 (HPTN Statistical and Data Management Center), and, UM1AI068613 (HPTN Laboratory Center). ViiV Healthcare and Gilead Sciences donated trial medications and matching placebos, and ViiV Healthcare provided additional funding.
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